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Abstract Introduction: Knee osteoarthritis is a debilitating disease that has been increasing in prevalence, especially due to the aging population and rising incidence of obesity. Biological therapies (orthobiologics) have emerged, demonstrating efficacy in improving functional scores, including the injection of microfragmented Adipose Tissue (mFAT). The purpose of this study is to evaluate the safety of adipose tissue harvesting and mFAT injection under local anesthesia. Materials/methods: A case series involving 34 patients who underwent adipose tissue collection from the abdomen under local anesthesia, without sedation, in a sterile environment, and who received the infiltration of microfragmented adipose tissue after single-time preparation, using a fat washing and microfragmentation kit. Results: Evaluation was performed at the time of the procedure and after 7 days of follow-up. Only ecchymosis (76.5 %) and mild discomfort at the harvested site (70.6 %), as well as mild discomfort at the infiltrated knee (61.8 %), were identified. No major adverse events were identified. Conclusion: The harvesting and injection of mFAT under local anesthesia is safe, with no major adverse events identified during this procedure.

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Abstract Introduction: Cervical Human Papillomavirus (HPV) infection, a common sexually transmitted infection, can lead to cervical cancer. This study investigates the impact of Photodynamic Therapy (PDT) on cellular immune function in cervical HPV-infected patients. Methods: From October 2022 to February 2023, 60 patients with cervical HPV infection were randomly assigned to a control group (conventional treatment) or a PDT group (PDT treatment), each with 30 patients. Peripheral blood samples and cervical tissue were collected before treatment, at 3 months, and at 6 months post-treatment. Flow cytometry assessed T-cell subsets (CD4+, CD8+, CD3+), and ELISA measured cytokine levels (TNF-α, IL-6, IL-8). Results: Baseline characteristics were similar between the PDT and control groups. The PDT group showed significantly higher HPV clearance rates at 3-months (70.00 %) and 6 months (100.00 %) compared to the control group 43.33 % and 80.00 %, respectively (p < 0.05). PDT significantly increased CD3+ and CD4+ cell levels at 3- and 6-months post-treatment compared to controls (p < 0.05). CD8+ levels and the CD4+/CD8+ ratio also significantly increased in the PDT group at 6 months. Additionally, PDT significantly reduced IL-6, IL-8, and TNF-α levels at 3- and 6-months post-treatment (p < 0.05). Conclusion: PDT enhances cellular immune function in cervical HPV-infected patients by increasing CD4+ and CD8+ T-cells and reducing pro-inflammatory cytokines. These findings highlight the potential of PDT in modulating immune responses and improving therapeutic strategies for cervical HPV infection.

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Abstract Introduction: The use of Hormone Dosage (HD) in Fine Needle Aspiration Biopsy (FNA) needle washout fluid, introduced in the 1990s, initially aimed at measuring Thyroglobulin (TG). Elevated TG concentration in an extrathyroidal cervical lesion suggests metastases of Well-Differentiated Thyroid Carcinomas (WDTC). Over the years, HD has evolved to incorporate Calcitonin (CT) and Parathormone (PTH), improving sensitivity and specificity in diverse clinical scenarios. Despite varying cutoffs in the literature, existing data underscore significant advancements in diagnostic accuracy. Methods: This paper presents a case series of 762 cervical lesions with FNA cytology and HD in different cervical regions. Results: It was possible to establish the histogenesis of the lesion based on a combination of the FNA cytology and PTH HD findings, so PTH was useful to determine parathyroid origin in all regions, Thyroglobulin (TG) and PTH together provide insights on cell origin in difficult cases. Thyroglobulin (TG) dosage enhances the accuracy of detecting well-differentiated thyroid carcinomas. In post-thyroidectomy by bed lesions, dosages help to determine non-thyroid/parathyroid lesions. Discussion: The case series and review underscore the valuable contribution of HD in fine-needle aspiration for the evaluation of cervical lesions. By integrating HD with cytological, ultrasound, and clinical data, clinicians can enhance the accuracy and specificity of FNA in diagnosing various cervical lesions, ultimately improving patient care and management.

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Abstract Background and aim: Malignant hilar obstruction usually presents in advanced-stage disease with a poor prognosis. Effective biliary drainage is essential for the beginning of palliative chemotherapy. There is a debate on the amount of liver parenchyma that should be drained to achieve clinical success. This study aimed to correlate the volume of liver drained with clinical success rate. Methods: The authors conducted a retrospective study including patients with malignant hilar biliary obstruction who underwent retrograde endoscopic cholangiography for biliary drainage from January 2014 to December 2018. The main outcome was a correlation of clinical success rate with hepatic volume drained. Secondary outcomes were correlation of clinical success rate with the quantity of liver sectors drained and unilateral versus bilateral drainage. Results: 82 patients met inclusion criteria (58.5 % female), with a mean age of 60±13 years. The main cause of hilar obstruction was cholangiocarcinoma (32.9 %) followed by lymph node metastasis (23.2 %). Technical success was achieved in 75 patients (91.5 %), and clinical success in 45 patients (60 %). The authors found a significant correlation between clinical success rate when at least 50 % of viable parenchyma was drained (p = 0.016; OR = 4.15, 95 % CI 1.4–12.5). Considering liver sectors, higher clinical success rates were found when at least 2 sectors were drained (p < 0.001; OR = 8.50, 95 % CI 2.7–26.7). The correlation between unilateral versus bilateral drainage and clinical success was not statistically significant. Conclusion: Drainage of at least 50 % of volume hepatic parenchyma was associated with better outcomes as well as drainage of at least 2 hepatic sectors, regardless of if unilateral or bilateral.

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Abstract Background: Lactylation plays an essential role in pancreatic cancer, but the precise role of lactylated histone in the diagnosis and prognosis of pancreatic cancer remains to be further clarified. Methods: Twenty-one patients diagnosed with pancreatic cancer were enrolled in this study, and the clinico-pathologic characteristics were collected. Lactylation levels of total proteins and histone H3 Lysine-18 (H3K18) of tissues were determined by western blotting and laboratory indicators including serum levels of lactate, Cancer Antigen 19–9 (CA19–9), and Carcinoembryogenic Antigen (CEA) were obtained. Results: Total protein lactylation was found in both pancreatic cancer tissues and para-carcinoma normal tissues, and was more potent in tumor tissues. H3K18la was also highly expressed tumor tissues. Furthermore, H3K18la protein expression correlated positively with serum lactate (r = 0.774, p < 0.001), CA19–9 (r = 0.744, p < 0.001), and CEA (r = 0.589, p < 0.01). The Area Under the Curve (AUC) of H3K18la for the diagnosis of pancreatic cancer was 0.848 in serum (p < 0.001). Conclusion: The present findings suggested that H3K18 may be used as a novel potential biomarker for the diagnosis and prognosis of pancreatic cancer patients.

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Abstract Background: Primary Health Care (PHC) plays a pivotal role in the healthcare system as the initial point of contact for users and patients. In the healthcare area, claims are presented and managed through a web app. It also enables systematic analysis of emerging information to drive continuous improvement. The present objective was to describe the complaints filed at PHC in 2022. Methods: A cross-sectional study was conducted, examining complaints filed by patients in 2022. For inclusion of the complaints, it was established that it had to do with the treatment received by healthcare personnel and that was presented through the web app. Complaint texts signaling dissatisfaction with the information received were subjected to qualitative coding. Results: The study involved 326 users who submitted a total of 358 complaints specifically related to treatment and information. The average age of the participants was 33.5 ± 16.2 years, and the majority were women (72.4 %, n = 236). In 2022, the Cumulative Incidence (CCI) was 55.2 complaints per 100,000 healthcare act and the Complaint Incidence Rate (CIR), defined as the number of complaints/1000 users/year, was 6.5. The prevalence of complaints related to information was 12.4 %. The main reasons for complaints about information were issues related to communication with the patient (79 %), followed by the patient’s disagreement with the techniques applied by healthcare staff (17 %). Conclusions: Results show us the fundamental characteristics of complaints in primary care with respect to the information received by health professionals, not allowing us to know where the authors can influence through interventions or training actions to try to improve.

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Abstract Introduction: The Marginal Mandibular Nerve (MMN), despite being didactically described as being a unique branch of the other branches of the Facial Nerve, has in practice an abundant anatomical variation. Both in relation to its ramifications and the positioning of these in relation to the lower edge of the mandible, as well as its anastomoses along its path, play a fundamental role in the surgical strategy during the approach of this cervicofacial site, and can generate, as underestimated its characteristics, inadvertent injuries and motor consequences to the patient. Objective: To analyze the types of anatomical variations of the MMN in relation to its position, ramification, and distance from reference points, as well as its incidence that could imply technical difficulties in surgery. Methods: A systematic review was conducted in the literature in search of anatomical studies, in vivo or in cadavers, between 1981 and 2024, which described the quantification of the MMN branches, their positioning and peculiarities in relation to anastomoses with other peripheral nerves. Results: 511 hemifaces were studied, with the identification of 290 cases of single nerve, 160 cases of double branch, 54 cases of triple branch, and 7 cases of quadruple branch. Of the 456 nerves that were possible to study, the average distance when superior to the lower limit of the mandible was 1.61 cm, while its lower analysis was 2.53 cm. The branches presented different proportions of presentation in relation to this reference point depending on how many branches it had, being more common to remain below it. Anastomoses were identified between the MMN and the buccal and cervical branch of the Facial Nerve, as well as with the Trigeminal Nerve. Conclusion: The varied presentations of the MMN, both in its anatomical positioning and in the number of branches leads us to question whether the surgical thinking when performing an exploration in this site may not be the reason whythe authors verify several motor complaints superior to described injuries.

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Abstract Background: The study was to investigate circRBM33 in septic acute lung injury (ALI). Methods: Treatment of Murine Lung Epithelial-12 cells (MLE-12) cells was performed using 10 ng/mL Lipopolysaccharide (LPS). circRBM33, miR-15a-5p, and Enhancer of zeste homolog 1 (EZH1) were ascertained through RT-qPCR or Western blot analysis. The viability of MLE-12 cells was measured using the MTT assay, and their rate of apoptosis was ascertained through flow cytometry. B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X (Bax) were determined using Western blot analysis. Oxidative stress levels were assessed with ELISA kits, and levels of malondialdehyde(MDA) content, Superoxide Dismutase (SOD) activity, and glutathione (GSH) were detected. Dual luciferase reporter gene and RIP assays verified the targeting link between miR-15a-5p and circRBM33 or EZH1. The role of circRBM33 in ALI in vivo was determined by performing cecum ligationperforation (CLP) surgery. HE staining, W/D pulmonary edema, and histological damage scores were taken to assess the extent of lung tissue damage. ELISA was performed to determine proinflammatory factors in lung tissue and cells. Results: CircRBM33 downregulation ameliorated ALI-induced edema, apoptotic, and inflammatory reactions in mouse lung tissues. In addition, apoptosis and inflammation mediated by LPS in MLE-12 cells were ameliorated by circRBM33 downregulation, whereas miR-15a-5p knockdown or EZH1 elevation eliminated the action of silencing circRBM33. circRBM33 mediated EZH1 expression by competitive adsorption of miR-15a-5p. Conclusion: CircRBM33 improves ALI in septic mice by targeting the miR-15a-5p/EZH1 axis.

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Abstract Objective: To investigate the effect of Mometasone furoate (Elocon Cream) Nasal Spray (MFNS) treatment on hearing secretory Otitis Media (SOM) in younger children. Methods: Seventy-six children with SOM (ages 5 to 10 years-old) were selected as study subjects and divided into two groups of 38 cases each using a randomized numerical table. The control group was given conventional treatment, and the observation group was treated with MFNS based on the control group. Both groups were treated for 12 weeks. The improvements in clinical symptoms and hearing were compared between the two groups at weeks 4, 8 and 12 of treatment, respectively. Results: The total effective rate of treatment in the observation group was higher than that in the control group. The middle ear resonance frequency of the children in the observation group was higher than that of the control group at weeks 4, 8 and 12 of treatment, and the air-conduction hearing threshold was lower than that of the control group. The total effective rate of the observation group after 12-weeks of treatment was 92.11 %, which was significantly higher than that of the control group (73.68 %). In addition, the T-ETDQ score of the observation group was lower than that of the control group after treatment. Conclusion: MFNS has clinical efficacy in the treatment of SOM in young children, which can improve clinical symptoms, promote the recovery of hearing and eustachian tube function, reduce the local inflammatory response, and improve immune function.

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Abstract Objective: To investigate the clinical and swallowing profiles of patients with post-intubation tracheal or laryngotracheal stenosis requiring tracheostomy prior to surgical or corrective airway interventions. Methods: A retrospective cohort clinical study. Patients who met the inclusion criteria underwent a swallowing evaluation, as well as imaging studies of the neck and chest. At 6 and 12-months after the initial assessment, all patients participated in follow-up speech pathology consultations to evaluate the current state of swallowing and the progress of airway stenosis treatment. Results: Twenty-five patients with a median tracheostomy duration of 30.52 months were assessed. The study found a female predominance (68%) and a high prevalence of subglottic stenosis (44%). Most patients required intubation due to severe acute respiratory failure and airway protection due to a decreased level of consciousness. Imaging revealed additional airway abnormalities, including laryngotracheobronchitis and laryngeal edema. Swallowing assessments showed that 20% had significant dysphagia. After one year, only two patients were successfully decannulated, while others remained tracheostomy dependent. Conclusion: The study underscores the need for personalized, multidisciplinary care for these patients. It finds that while treatments like reconstructive surgeries and the Montgomery T-tube can be effective, complications such as clinical instability and dysphagia can worsen outcomes and extend the need for tracheostomy.

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Abstract Introduction This study aimed to investigate the associations among seizures, clinical characteristics, and brain injury on Magnetic Resonance Imaging (MRI) in infants with Hypoxic Ischemic Encephalopathy (HIE), and to determine whether these findings can predict unfavorable neurodevelopmental outcomes. Method Clinical and electrographic seizures were assessed by amplitude-integrated electroencephalogram, and the extent of brain injury was evaluated by using MRI. At 12‒24 months of age, developmental impairment or death was assessed. Between 2012 and 2020, 143 newborns were admitted for HIE, and 8 infants were excluded from the study. Results Eighty-five infants were diagnosed with greater than moderate HIE and 65 infants underwent therapeutic hypothermia. In addition, 38 infants experienced clinical seizures (clinical seizure group, CSG), 49 infants had electrographic seizures (Electrographic Seizure Group, ESG), and 48 infants had no seizures (no seizure group, NSG). The proportion of infants with neurodevelopmental impairment or death was significantly higher in the CSG than in the NSG (57.7 % and 26.1 %, p = 0.026). A risk factor analysis indicated that cord blood pH (adjusted Odds Ratio [aOR = 0.01]; 95 % Confidence Interval [95 % CI 0.001‒0.38]; p = 0.015) and MRI findings (aOR = 4.37; 95 % CI 1.25‒15.30; p = 0.012) were independently associated with abnormal neurodevelopment, after adjustment. Discussion Clinical seizures in infants with HIE were independently associated with abnormal neurodevelopment. However, cord blood pH and abnormal brain MRI findings were consistently linked to long-term neurodevelopmental outcomes.

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Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is a common chronic respiratory disease with a long course and recurrent symptoms, seriously affecting patients' quality of life. Objectives This study aimed to explore the interventional value of eight-section brocade exercises in combination with comprehensive measures of the physical function status of patients with COPD. Method This is a retrospective study. A total of 94 COPD patients admitted to the studied hospital were divided into two groups according to different intervention methods. The control group was treated with comprehensive intervention, and the research group received eight-section brocade exercises combined with comprehensive intervention. Results After an intervention, the research group exhibited longer exercise endurance time (p < 0.05); the modified Medical Research Council (mMRC) scores and quality of life scores in the research group were lower than those in the control group (p < 0.05); sleep quality scores of the research group being lower than those of the control group (p < 0.05); both groups experienced a decrease in adverse emotion scores, with the research group scoring lower than the control group (p < 0.05); the research group achieving better physical function status than the control group (p < 0.05); the nursing efficiency rate and satisfaction rate in the research group was higher than those in the control group (p < 0.05). Conclusions Eight-section brocade exercises can enhance the exercise endurance of and improve the lung function of COPD patients, which is of great significance for the recovery of patients’ physical function.

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Abstract Objective To investigate the value of Contrast-Enhanced Ultrasound (CEUS) combined with Procalcitonin (PCT) in differentiating Tuberculous Lymph Nodes (TLN) from Metastatic Lymph Nodes (MLN). Methods This prospective cohort study included 207 consecutive patients diagnosed with CTL. Before confirming through pathology or laboratory tests, every patient received standard ultrasound, CEUS, and MRI examinations, with the imaging results analyzed afterward. Serum indicators were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Predictive modeling was performed by multifactorial logistic regression. Evaluate the diagnostic and calibration performance of the predictive model by drawing Receiver Operating Characteristic (ROC) curves and calibration curves, and using Area Under the Curve (AUC) and Hosmer-Lemeshow (H-L) tests. Results The presence of lymph node lesions was confirmed by routine ultrasound and MRI in 207 patients, of which 102 (49.27 %) had a pathological or laboratory diagnosis of metastatic lymph nodes (MLN), and 50.8 % were tuberculous lymph nodes (TLN). According to imaging findings of CEUS, TLN was more commonly associated with enhanced concentric performance in the arterial phase (67.65 % vs. 40.95 %) and heterogeneous enhancement pattern in lymph nodes (70.59 % vs. 52.38 %). Peak Intensity (PI) of lesions was higher in patients with MLN. Increased age-enhanced concentric performance in the arterial phase, increased PI, and serum PCT greater than 5.39 ng/mL were independent risk factors for MLN. The prediction model of serum PCT combined with CEUS had a higher diagnostic value for MLN. The H-L test indicated a satisfactory model fit (all p > 0.05), and the calibration curve closely approximates the ideal diagonal. Conclusion CEUS combined with serum PCT has better clinical application value in the differential diagnosis of TLN and MLN.

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Abstract Objective Based on Toll Like Receptor 4 (TLR4)/Nuclear Factor-κB (NF-κB) Exploring the effects of Licochalcone A (LCA) on the proliferation, invasion, and drug resistance of glioma cells through signaling pathways. Methods Cultivate human glioma cell line U251 in vitro, induce drug-resistant cell line U251/TMZ with Temozolomide (TMZ), and validate the results. Different concentrations of licorice chalcone A were used to treat U251 cells and U251/TMZ cells, and were named as control group, low-dose group, medium-dose group, and high-dose group, respectively. CCK-8 assay, cell adhesion assay, and Transwell assay were used to detect cell survival rate, cell adhesion rate, number of migrating cells, and number of invading cells, respectively. Results The cell survival rate, cell adhesion rate, number of migrating and invading cells in the high-dose group were lower than those in the medium-dose group and lower than those in the control group. High-dose group TLR4, NF-κB mRNA and protein levels were lower than those in the medium dose group and lower than those in the control group (p < 0.05). Compared with the si-NC group, the si-TLR4 group showed a decrease in cell survival rate and adhesion rate, as well as a decrease in the number of migrating and invading cells, the levels of CyclinD1 and N-cadherin proteins decreased, while the levels of E-cadherin protein increased (p < 0.05). Conclusion LCA could inhibit the proliferation and metastasis of glioma cells and reverse drug resistance, possibly by inhibiting the TLR4/NF-κB signaling pathway.

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Abstract Background Gastric Cancer (GC) was the third highest mortality rate among malignant tumors. Currently, no specific treatment is utilized to prevent the progression of GC. The detailed mechanism of GC was still elusive and this study aimed to clarify the mechanism of GC occurrence and development. Method This study was performed to clarify the molecular mechanisms of CST1 promoting GC development through activating AKT. The normal gastric tissue cells and GC cell was obtained, followed by transfection with oe-CST1 or sh-CST1, and their apoptosis and viability were evaluated. Finally, Western blot, Flow cytometry assay, Transwell assay, and Scratch assay were used to elucidate the molecular mechanisms of CST1 promoting GC development through activating the AKT pathway. Results Research outcomes show a significant elevation in CST1 and AKT protein as well as mRNA quantities in both the model and CST1-activator cohorts in relation to the control. Conversely, these proteins and mRNA concentrations were notably decreased in the presence of the CST1 inhibitor when compared to the model group, a difference that was statistically significant as evidenced by the p-value. Conclusion CST1 can promote the gastric cancer process by targeting the AKT pathway.

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ABSTRACT Background Hospitalization for Transurethral Prostate Resection (TURP) involves circadian rhythm disturbance - a possible cause of Postoperative Neurocognitive Disorder (POCD) in elderly patients. This study investigated whether melatonin ameliorated this effect. Methods A double-blind, randomized clinical trial used a battery of neuropsychological tests to evaluate cognitive performance of 118 patients aged ≥ 60, before TURP with spinal anesthesia, and at 21- and 180-days PO. Patients received 10 mg of melatonin, or a placebo, on the night before surgery and 1-, 2- and 3-days PO. Delayed neurocognitive recovery in the two groups at 21 days PO was compared using the Chi-Squared test; individual performances in each test at each date were compared using the General Mixed Model. Results with p < 0.05 were considered significant. Results Pre-surgery, both groups had significant cognitive deficits. Delayed cognitive recovery at 21 days PO was the same in both. There were no cases of POCD at 180 days. The melatonin group performed better in the delayed-recall FOME, which assesses memory, and in the Digit Span test, which assesses attention and cognitive flexibility. Unexpectedly, global neurocognitive performance was improved at 180 PO in both groups. Conclusions Melatonin had no statistical effect on POCD, but a selective beneficial effect was observed in two cognitive areas. The high prevalence of preoperative cognitive impairment may be related to the lower urinary tract symptoms which were reasons for the surgery; the unexpected improvement of cognitive performance in all patients at 180 days PO may reflect alleviation of these symptoms.

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Abstract Mycobacteria infections are caused by species of the Mycobacterium tuberculosis complex (MTB) and other species called Non-Tuberculosis Mycobacteria (NTM). Identification of mycobacteria species is very important to define treatment and it can be achieved by direct culture. However, the lack of clear protocols regarding the use of culture or molecular tests on specimens diagnosed with granulomatous lesions causes delays in the diagnosis of the etiological agents and, consequently, the definition of the right treatment. This work aimed to characterize the incidence of mycobacteria species in pulmonary granulomatous lesions and the contribution of Polymerase Chain Reaction (PCR) in Formalin-Fixed Paraffin-Embedded Tissue (FFPE), direct culture, and Ziehl-Neelsen histological stain to the diagnosis. The authors performed an observational, centralized, and retrospective study in a cohort of 336 cases with pulmonary granulomatous lesions. Mycobacteria were detected by ZNS in 54/323 (16.72 %) and by direct culture in 40/198 (20.20 %). MTB DNA was detected by PCR in 10/57 (17.54 %). Mycobacterial culture results revealed MTB in 26/40 (65.00 %), whereas NTM was detected in 13/40 (32.50 %). NTM was represented by M. avium (n = 4), M. intracellulare (n = 3), M. kansasii (n = 3), M. colombiense (n = 1), M. paraffinicum (n = 1), and M. abscessus subsp. massiliense (n = 1). In conclusion, this study demonstrated that mycobacteria are detected in 16.72 % to 20.20 % of pulmonary granulomatous lesions. Moreover, MTB and NTM were detected in these lesions. The use of different methods for mycobacteria detection, in addition to culture, is complementary and contributes to fastening and increasing the detection of mycobacteria in these lesions.

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Abstract Introduction People Living with Human Immunodeficiency Virus (PLHIV) appear to be at a higher risk of developing sarcopenia. Various factors seem to influence the risk of sarcopenia, and its prevalence may differ depending on the screening tool used. This study aimed to (i) Screen the risk of sarcopenia in PLHIV using the SARC-F and SARC-Calf and identify associated factors; (ii) Analyze the agreement between the instruments in PLHIV. Methods Cross-sectional study including PLHIV taking antiretroviral therapy. The authors assessed sarcopenia risk using the SARC-F and SARC-Calf tools with ≥4 and ≥11 cutoff points, respectively, and a wide spectrum of variables was analyzed. Results Participated 76 patients (44.9 ± 12.7 years). Sarcopenia risk, according to the SARC-F, was 27.6 % and was associated with socioeconomic status (p = 0.004), smoking (p = 0.001), disease status (p < 0.001), opportunistic infections (p = 0.001), CD4 T-cell count (p < 0.001), Handgrip Strength (HGS) (p < 0.001), and Gait Speed (GS) (p = 0,001). Using the SARC-Calf, sarcopenia risk was 36.8 % and was associated with work activity (p = 0.029), socioeconomic status (p = 0.004), smoking (p = 0.009), disease status (p < 0.001), opportunistic infections (p = 0.015), CD4 T-cell count (p = 0.002), HGS (p = 0.001), Appendicular Skeletal Muscle Mass Index (ASMMI) (p = 0.009), and GS (p < 0.001). The agreement between tools was moderate (k = 0.49). Conclusion Sarcopenia risk, as determined by both tools, was higher in low-income PLHIV with opportunistic infections, CD4 T-cell count ≤ 200 cells/mm3, low HGS, and low GS, and lower in asymptomatic and non-smoking individuals. The authors recommend investigating these factors in hospital and outpatient settings. The SARC-Calf proved to be more appropriate for screening sarcopenia risk in PLHIV.

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Abstract Background Fibroadenomas are common benign breast lumps that can cause anxiety due to malignancy concerns, and Centchroman, a selective estrogen receptor modulator, has shown promise in reducing their size. This study aimed to evaluate the efficacy of Centchroman in reducing fibroadenoma size, mastalgia, anxiety, and depression in affected patients. Methodology A parallel-arm randomized controlled trial was conducted at a tertiary care Breast Clinic with 104 patients aged 18‒45 years having fibroadenomas ≤ 3 cm. Group A received Centchroman (30 mg on alternate days) and Group B received a placebo for 12 weeks. The primary outcome was fibroadenoma volume reduction measured by ultrasound, while secondary outcomes included reductions in mastalgia and improvements in anxiety and depression (HADS scores). Results Both groups showed fibroadenoma volume reduction over 12-weeks, with a greater reduction in the intervention group (3.67 ± 1.65 cm3 to 2.29 ± 1.04 cm3) than the control group (3.12 ± 1.16 cm3 to 2.73 ± 0.78 cm3), though the difference was not statistically significant (p = 0.342 and p = 0.781). However, 28.8 % of the intervention group experienced over 50 % volume reduction compared to 13.5 % in the control group (p = 0.007). Mastalgia significantly improved in the intervention group (VAS: 5.76 ± 2.13 to 2.24 ± 0.93, p = 0.023), with minimal improvement in controls. Anxiety and depression scores significantly decreased in the intervention group, with anxiety dropping from 9 to 5 and depression from 6 to 4 (p = 0.001). Conclusion Centchroman effectively reduces fibroadenoma size especially those with multiple fibroadenoma, mastalgia, and psychological distress in patients with fibroadenoma.

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Abstract Objective Acute Pulmonary Embolism (APE) is a disease with increasing incidence worldwide. Antithrombotics are the cornerstone of the treatment. Bleeding is an adverse event related to this therapy. The objective was to evaluate the prevalence of bleeding in a sample of Brazilian patients hospitalized with APE and the impact of this complication on mortality. Additionally, the performance of some bleeding predictive scores was evaluated in this sample. Methods A retrospective cohort study was carried out on patients hospitalized with APE from January 2009 through August 2017. The medical records of these patients were reviewed, and the bleeding recorded during hospital stay was classified according to the “Thrombolysis in Myocardial Infarction (TIMI) bleeding risk.” Five different predictive scores for bleeding after APE (RIETE, PE-SARD, VTE-BLEED, Kuijer, and ATRIA) were applied. Overall mortality at 30 days and one year were assessed. Results One hundred fifty-nine patients were included. The prevalence of any bleeding was 36/159 (23 %), major bleeding was 10/159 (06 %), minor bleeding was 11/159 (07 %), and bleeding requiring attention was 15/159 (10 %). Only major bleeding was associated with higher mortality at one-year follow-up with a Relative Risk (RR) of 2.00 (95 % CI 1.16-3.57; p = 0.044). All bleeding predictive scores evaluated showed low accuracy in identifying patients at higher risk of bleeding. Conclusion Patients hospitalized with APE in Brazil had a high prevalence of bleeding. The major bleeding increased the one-year mortality. The bleeding predictive scores assessed showed limited accuracy in identifying patients at high risk of bleeding.

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Abstract Background Sevoflurane (Sev) is an inhalational anesthetic for surgical procedures where it can trigger cognitive dysfunction and neuronal apoptosis. Gyosaponin (GpS) was studied for its effects on brain morphology and cognitive behaviors in Sev-anesthetized rats. Methods Male Sprague-Dawley rats were induced by 3 % Sev anesthesia, and 25 mg/kg and 100 mg/kg GpS were injected into the rats by tail vein. The in vitro model of Sev anesthesia was constructed by treating primary rat hippocampal neurons with 4.1 % Sev in the presence of GpS (5, 10, and 20 μM). The neuroprotective effects of GpS against Sev-induced cognitive deficits in rats were evaluated using the open field and Morris water maze tests. The apoptosis of hippocampal neurons was observed using HE staining and TUNEL assay. Apoptosis-related proteins and proteins related to the PI3K/Akt/mTOR pathway were determined via Western blot. Also, pro-inflammatory factors were measured via ELISA. Results GpS diminished the Sev-triggered apoptosis in neurons and Cleaved caspase-3, BAX, TNF-α, IL-6, lessened oxidative stress damage, and stimulated the PI3K/Akt/mTOR pathway. GpS therapy markedly enhanced learning and memory abilities in rats suffering from Sev-related cognitive impairments. Conclusion GpS ameliorates Sev-induced neurotoxicity and cognitive dysfunction by modulating the PI3K/Akt/mTOR pathway and alleviating neuronal apoptosis and oxidative stress.

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Highlights OSVE and multiple-choice tests can be used interchangeably in the context of formative assessment. OSVE and multiple-choice tests as effective tools to enhance intern training and monitoring. OSVE holds promise as a transformative tool, capable of ensuring the continuity and integrity of clinical skills assessment in medical education.

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Highlights We identified a distinctive pattern of serum metabolic signatures in juvenile idiopathic arthritis patients under methotrexate therapy. Methotrexate use is associated with a more efficient mitochondrial function. A decreased mitochondrial metabolism was observed in polyarticular and systemic JIA subtypes, with a decrease of several acylcarnitines’ concentrations.

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Highlights Renal Doppler marker variations within the initial 24 h in sepsis patients. RRI reduction after 24h of ICU treatment can be used for early detection of SA-AKI. Critical ultrasound for dynamic monitoring of renal perfusion.

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Highlights Incidence of frailty in elderly patients varies widely among different tools. FP and FS could be employed as tools for predicting frail conditions. Different tools had low consistency in predicting frail conditions.

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Highlights Question - Extension of the biliopancreatic loop increases l-cell activity after surgery bariatric? Findings - l-cell activity increased independent of extension of the biliopancreatic limb. Meaning - The additional beneficial effects of long BPL may be due to more rapid delivery of food and bile salts to more distal portions of the intestine.

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Highlights Guidelines recommended pulmonary rehabilitation in COPD. Self-driven pulmonary rehabilitation is an undertreatment for COPD patients in China. Chinese patients with COPD have worse clinical conditions. Treatment with pulmonary rehabilitation at institutes improves clinical outcomes. Chinese COPD patients are required to be treated as per proper guidelines.

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Highlights After cataract surgery, the prevalence rate of Descemet membrane Detachment was significantly higher in the group with keratome incisions (63.2 %) compared to that with femtolaser incisions (22.2 %).

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Highlights Restless legs syndrome is associated with lower information processing speed. Obstructive sleep apnea is not associated with lower information processing speed. Managing sleep disorders is critical for improving cognition in multiple sclerosis.

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Highlights Adverse effects of lenalidomide for Newly Diagnosed Multiple Myeloma (NDMM) cannot be ignored. Lower-dose PLD administered with dexamethasone and subcutaneous bortezomib is associated with a good durable response. Lenalidomide is retained as maintenance or salvage therapy if the DVD regimen fails.

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Highlight TRIB3 over-expression was related to the poor prognosis of LSCC. Patients with methylation related to high TRIB3 expression had a poorer prognosis. Knock-down of TRIB3 expression suppresses the growth, invasion and migration of LSCCs via PI3K- AKT- mTOR. TRIB3 may be viewed as a possible cancer biomarker.

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Highlights hsa_circ_0000105 modulates malignancy of NPC cells. hsa_circ_0000105 influences the malignant behavior of NPC via downstream miR-541-3p. hsa_circ_0000105 positively regulates S100A11 to accelerate the malignant behavior of NPC. hsa_circ_0000105 inhibits NPC tumor growth in vivo.

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Highlights Dry eye is more frequent in the urban than in the rural population. Dry eye is associated with dyslipidemia, visual display terminal, and ocular surface problems. Dry eye is more frequent in women and the associated factors are associated with antiallergics, chronic pelvic pain, and fibromyalgia. Dry eye in the elderly has distinct clinical associated factors.

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Highlights Stem cell therapy is a promising alternative in the spinal cord injury arsenal. Challenges in stem cell treatment in SCI: phase uncertainty and cell type controversy. Umbilical cord mononuclear cells may enhance recovery via multiple mechanisms. Umbilical cord mononuclear cells can promote histological improvement after SCI.

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Highlights Construction of a personalized risk prediction model for in-hospital mortality in patients with acute myocardial infarction undergoing Percutaneous Coronary Intervention (PCI). Identification of risk factors associated with in-hospital mortality in AMI patients who underwent PCI. Development of a nomogram prediction model for in-hospital mortality in AMI patients after emergency PCI. Evaluation of the nomogram model's effectiveness through c-index, internal validation, Hosmer-Lemeshow test, and calibration curve analysis.

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Highlights circLOC375190 reduction ameliorates neuronal autophagy and apoptosis in tMCAO mice. circLOC375190 knockdown improves OGD/R-mediated neuronal autophagy and apoptosis. circLOC375190 affects OGD/R-mediated neuronal apoptosis and autophagy by adsorbing miR-93-5p. circLOC375190 affects OGD/R-mediated neuronal apoptosis and autophagy by regulating the miR-93-5p/MKNK2 axis. circLOC375190 affects AIS autophagy by regulating the mTORC1/TFEB axis.

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Highlights Respiratory symptoms of PACS are associated with high serum Myl9 levels. Patients who have had COVID-19 can be divided into two groups according to their serum Myl9 levels. The neutrophil count is correlated with the Myl9 level at 6 months after infection.

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Highlights Correlation between pathologic complete response and endoluminal complete response. Half of pathologic complete responses do not achieve an endoluminal complete response. Gross findings do not perfectly reflect microscopic findings.

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Highlights NHANES data from 1999 to 2006 show a positive link between serum CRP levels and low muscle mass risk in US adults. An inverse J-shaped pattern emerges, indicating a non-linear association between CRP levels and low muscle mass risk, with critical points at 0.273 mg/dL for the overall population, 0.172 mg/dL for males, and 0.296 mg/dL for females. This nationally representative study underscores the crucial role of inflammation in muscle function and advocates for future research and clinical strategies to address inflammation's impact on muscle mass and function.

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Highlights ADSCs increased the viability (significantly less necrosis) of a TRAM flap in rats. Vessel formation in the ischemic segment of the flap was also enhanced by the ADSCs. Fluorescence microscopy indicated no differentiation of ADSCs into endothelial cells.

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Abstract Background and objective Colon Cancer (CC) is a common malignant tumor. The aim of this study was to investigate the role and regulatory mechanism of circular RNA pappalysin-1 (circ-PAPPA; hsa_circ_0088233) in CC. Methods In cancer tissues from CC patients, circ-PAPPA expression was measured and its relationship with patients’ clinical features was analyzed. Plasmid vectors or oligonucleotides interfering with the expression of circ-PAPPA, microRNA (miR)-656-3p or G-protein subunit Gamma-5 (GNG5) were transfected into CC cells. Cell viability was detected by MTT and colony formation assay; apoptosis was detected by flow cytometry; and cell migration and invasion were detected by wound healing assay and Transwell. Glycolytic capacity of CC cells was assessed by measuring glucose uptake and lactate production using commercial kits. The targeting relationship between miR-656-3p and circ-PAPPA or GNG5 was verified by bioinformatics website starBase and dual luciferase reporter gene assay assays. Results Circ-PAPPA was upregulated in CC and was negatively correlated with benign pathological features and 5-year survival rates of CC patients. Circ-PAPPA silencing inhibited the growth and glycolysis of CC cells through upregulating miR-656-3p. GNG5, a target of miR-656-3p, could reverse the impacts of silencing circ-PAPPA on CC cells. Conclusion Circ-PAPPA may play an oncogenic role in CC by promoting cell growth and glycolysis through the miR-656-3p/GNG5 axis.

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ABSTRACT Objective: This study investigated the predictive value of thrombin generation indices and Wells score in the development of Pulmonary Embolism (PE) in patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). Methods: 160 patients who were admitted for AECOPD and underwent CT Pulmonary Arteriography (CTPA) were collected. Among them, a total of 62 cases were diagnosed with PE as the AECOPD with PE group, and the other 98 cases were not diagnosed with PE as the AECOPD group. The general data, past history and combined basic diseases, laboratory tests and other related clinical data of the two groups were compared, and the data collected were statistically analyzed to explore the diagnostic indexes that can predict PE in AECOPD. Results: History of venous thromboembolism, D-Dimer as well as Endogenous Thrombin Potential (ETP), Activated Partial Thromboplastin Time (APTT) coagulation indices, and Wells score was significantly higher in the AECOPD with PE group than in the AECOPD group, and Time to Peak (ttpeak), Albumin (ALB) and total protein were lower than those in the AECOPD group. The Wells score had a positive correlation with ETP and APTT and a negative correlation with ttpeak, which were all independent risk factors for PE in AECOPD. The Wells score had the best efficacy in predicting the occurrence of PE in patients with AECOPD with a cutoff value of 4.62. Conclusion: Significant correlations were found between the thrombin generation indices (ETP, APTT and ttpeak) and the Wells score, which can also be used for early diagnosis of PE in patients with AECOPD.

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ABSTRACT Objective: To assess the performance of pembrolizumab for the treatment of Gestational Trophoblastic Neoplasia (GTN). Methods: The Medical Subject Headings related to immunotherapy/pembrolizumab and GTN were used alone or in combination to retrieve relevant articles. The authors searched in EMBASE, MEDLINE/PubMed, Elsevier’s Scopus, and Web of Science until November/2024. The authors included any randomized controlled trials, cohort studies, case series, and case reports focusing on pembrolizumab treatment in GTN. Meta-analysis of proportions was carried out employing a random-effects model. The meta-analysis employed the inverse variance method, with the arcsine link function for the analysis of proportional data. All analyses were performed using Stata 18. For all analyses, a p-value < 0.05 indicated statistical significance. This study was registered on PROSPERO (CRD42023493329). Results: A total of 550 studies were identified after a literature search among which 15 original studies were included in the systematic review and in the meta-analysis. Pembrolizumab induced complete sustained remission in 71.59% (95% CI 53.27-84.78%; I2 = 0.00%, H2 = 1.00, p = 0.90) of cases. The subgroups metaanalysis showed pembrolizumab had similar performance, regardless of age (< 40 vs. ≥ 40-years-old, p = 0.38), GTN histopathology (Placental Site Trophoblastic Tumor [PSTT], Epithelioid Trophoblastic Tumor [ETT]/ noninvasive mole/others versus invasive mole/choriocarcinoma, p = 0.48), time from diagnosis to the beginning of immunotherapy (< 4 vs. ≥ 4-years, p = 0.84), pembrolizumab combined with chemotherapy (yes vs. no, p = 0.66). Conclusions: Pembrolizumab seems an effective treatment for patients with high-risk GTN with chemoresistant or relapsed disease, including cases of PSTT/ETT, notwithstanding patient age, time to initiate immunotherapy and whether or not it was associated with chemotherapy.

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ABSTRACT To analyze whether there is a significant difference in the virulence, symptoms, and outcomes of different Coronavirus Disease 2019 (COVID-19) variants in children under 2-years of age. We collected data from the Sistema de Informação de Vigilância Epidemiológica da Gripe, a nationwide Brazilian database on severe acute respiratory syndrome. The patients were classified according to four variants of concern: wild-type, gamma, delta, and omicron. The wild-type variant was defined as the baseline. A total of 11,153 patients were analyzed. The risk of presenting dyspnea (adjusted Odds Ratio[Aor = 1.20], 95 % Confidence Interval [95 % CI 1.07-1.34]) was higher in patients with gamma infection. Respiratory discomfort was more likely to be present for the omicron (Aor = 1.29, 95 % CI 1.15-1.43) and gamma (aOR = 1.26, 95 % CI 1.13-1.41) infections. Desaturation was more likely to be present for the omicron (aOR = 1.67, 95 % CI 1.50-1.86), gamma (aOR = 1.16, 95 % CI 1.43-1.79), and delta (aOR 1.41, CI 95 % 1.18-1.68) infections. Infection by the omicron variant was a protective factor for intubation (aOR = 0.78, 95 % CI 0.67-0.91) and death (aOR = 0.43, 95 % CI 0.35-0.53). Additionally, delta infection was a protective factor against death (aOR = 0.60, 95 % CI 0.43-0.85). The wildtype variant was responsible for most of the cases that evolved with death. Omicron appears to be responsible for milder symptoms than delta. Children between 1 and 6 months of age account for most cases, which is a concern because there is no vaccination coverage.

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ABSTRACT Objective: This study aimed to determine whether ultrasound measurements of the hands could predict treatment failure in treatment-naive women with early rheumatoid arthritis. Method: In a prospective case-control study, 48 women underwent blind assessments four times over 48-weeks, considering three failure stages: failure 1 (methotrexate), failure 2 (leflunomide), and failure 3 (adalimumab). Bilateral ultrasound exams evaluated wrist, 2nd, and 3rd Metacarpophalangeal Joints (MCPs), and Proximal Interphalangeal Joints (PIPs) for inflammatory indicators (synovial and tenosynovial proliferation using grayscale and Power Doppler [PD]) and joint damage (bone erosion and cartilage damage). Results: The study involved 48 women, aged 47.7 ± 11.6 years, with an average disease duration of 7.5 ± 3.5 months. Of these, 41 (85.41 %) experienced failure 1, 25 (52 %) experienced failure 2, and 5 (10.5%) experienced failure 3. Predictors for failure 1 included PD/Q10 total score > 2.5 (OR = 18.00), PD/SQ10 total score > 5.0 (OR = 23.2), PD/Q MCP score > 1.5 (OR = 14.58), and PD/SQ MCP score > 3.0 (OR = 35). For failure 2, predictors encompassed PD/Q10 total score > 4.5 (OR = 4.81), PD/SQ10 total score > 9.5 (OR = 4.81), PD/Q MCP score > 2.5 (OR = 4.92), PD/SQ MCP score >5.0 (OR = 6.22), and PD/Q PIP score > 1.5 (OR = 6.66). In relation to failure 3, a PD/Q wrist score > 2.5 (AUC = 0.79; p = 0.035) was indicative. Conclusions: Power Doppler proved to be a predictive indicator for treatment failure in early rheumatoid arthritis among treatment-naive women. It emerged as a predictor for both the initial and 2nd DMARD treatments, as well as the 1st immunobiological treatment, based on hand joint assessments. Trial registration: Clinical trials.gov NCT04752748.

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ABSTRACT Objective: The aim of this study was to evaluate monocyte subtypes and the chemokine receptors, comparing individuals with and without Chronic Venous Insufficiency (CVI). Method: The authors included patients undergoing surgery for varicose veins of the lower limbs (Classification of Venous Disorders - CEAP: C1-C3). Results: There were increased levels of classical and non-classical monocytes in the case group and a reduction in intermediate monocytes. Besides, there was higher expression of CCR5 in the non-classical monocytes and lower expression of CX3CR1 in the classical monocytes in the case group. Conclusions: The inflammatory process present in patients with CVI can modulate the monocyte phenotype and the expression of the chemokine receptors at the protein level.

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ABSTRACT The incorporation of long-acting reversible contraceptives (LARCs) into reproductive health strategies is crucial for enhancing access to effective contraception and reducing unplanned pregnancies (UPs). Evidence shows that even a modest shift from short-acting methods to LARCs can yield significant cost savings and improve health outcomes, both for individuals and public health systems. By facilitating single-visit placements and expanding the training of multidisciplinary teams, including nurses, healthcare providers can increase access to these effective contraceptive options.

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ABSTRACT In response to the high false positive rate of traditional Low-Dose Computed Tomography (LDCT) in diagnosing pulmonary malignant nodules, this study aimed to investigate the effectiveness of scoring of blood-based noninvasive biological metabolite detection combined with artificial intelligent scoring of non-invasive imaging in the clinical diagnosis of Pulmonary Nodules (PNs). In this retrospective study, risk scoring was performed in patients positive for pulmonary nodules and subsequently, PNs were sampled by invasive procedures for pathological examinations. The pathological classification was used as the gold standard, and statistical and machine learning methods showed, that in 210 patients (23 benign PN and 187 malignant PN), the risk score of Metabonomics, radiomics, and multi-omics had different levels of performance in different risk groups based on various predictive models. The Area Under the receiver operating Characteristic Curve (AUC) of the multi-omics model was 0.823. The present results indicate that a multi-omics model is more effective than a single model in the non-invasive diagnosis of pulmonary malignant nodules.

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ABSTRACT Objective: This study aims to analyze the risk factors for depression in peritoneal dialysis patients and to develop a predictive nomogram model for assessing these risks. Methods: A total of 326 peritoneal dialysis patients treated between August 2021 and December 2023 were selected as the training set. These patients were categorized into a non-depression group (229 cases) and a depression group (97 cases) based on the presence of depression. Additionally, 104 peritoneal dialysis patients from the same period were selected as the validation set. Clinical data were collected from all patients for analysis. Results: The depression group had higher proportions of female patients, non-employed individuals, those with a per capita monthly income of <2000-yuan, cardiovascular complications, cerebrovascular complications, and sleep disorders compared to the non-depression group. Additionally, the levels of hemoglobin and blood uric acid were lower in the depression group than in the non-depression group (p < 0.05). Gender, work status, per capita monthly income, cardiovascular complications, cerebrovascular complications, and sleep disorders are risk factors for depression in peritoneal dialysis patients (p < 0.05), while hemoglobin and blood uric acid are protective factors for depression in peritoneal dialysis patients (p < 0.05). Calibration curve analysis results showed that the predicted probability was basically consistent with the actual incidence rate. The results of the Decision Curve Analysis (DCA) demonstrated that the nomogram model developed in this study has strong clinical applicability. Conclusion: The nomogram model for predicting depression in peritoneal dialysis patients, which incorporates factors such as gender, work status, per capita monthly income, cardiovascular complications, cerebrovascular complications, sleep disorders, hemoglobin levels, and blood uric acid levels, demonstrates excellent calibration and discrimination. Additionally, it has high clinical applicability.

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ABSTRACT Objectives: The primary goal of this study is to evaluate the educational effects of medical students’ participation in a health expedition project. Specific objectives include assessing students’ perceptions of the educational value of the program, measuring gains in clinical knowledge and skills, evaluating behavioral changes, professional orientation, and students’ willingness to work within the public health system (SUS) after graduation. Methods: A quantitative methodology was employed, following Kirkpatrick’s four-level evaluation model. Questionnaires were administered before and after participation in the expedition to assess students’ reactions, learning, and empathy. The sample comprised all 15 students who participated in the expedition, with data analysis performed using R software. Results: The analysis highlighted that the expedition experience significantly impacted student’s career trajectories. Approximately 80 % of participants reported that the expedition positively influenced their career decisions, and 60 % expressed interest in working within the SUS. These findings suggest that while expeditions may not yield quantifiable gains in clinical competence in the short term, they can be catalysts in forming physicians oriented towards public service and social sensitivity. Conclusions: Health expeditions like the one conducted may not offer significant improvements in measurable clinical competencies in the short term but have a substantial effect on students’ career decisions, aligning with public health needs and reinforcing commitment to service in vulnerable contexts. This influence suggests that practical experiences in community settings play a crucial role in shaping medical students’ professional aspirations, emphasizing the importance of such programs in medical education aimed at social responsibility and health equity.

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ABSTRACT Introduction: The uterine leiomyoma is a pelvic solid tumor more frequent in women. The Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) is a technique aimed at diminishing hypermenorrhagia and dysmenorrhea in symptomatic women. Objective: To show the effects subsequent to MRgFUS application on symptoms, quality of life, and myoma volume in symptomatic women. Methods: Fifty-two patients with symptomatic uterine myomas underwent MRgFUS followed by clinical evaluation, pelvis MRI, and administration of the UFS-QoL questionnaire at 6 months and 12 months to detect symptom improvements and decrease in myoma volume. Results: The mean myoma volume decreased 24 % after 6 months and 42 % after 12 months. The mean score on the UFS-QoL questionnaire increased 54 % after 6 months and 81 % after 12 months. There were no serious complications. Four patients had first-degree burns. No infection cases were reported. Two patients progressed to a myomectomy by surgical hysteroscopy and one of them underwent total hysterectomy 11 months after the MRgFUS treatment. Conclusion: This case series suggests that MRgFUS therapy is viable and effective in reducing symptoms and improving the life quality of symptomatic patients.

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ABSTRACT Objective: In the fight against Colorectal Cancer (CRC), chemotherapy resistance is a major obstacle. Therefore, it is imperative to identify effective biomarker therapeutics. Despite microRNAs (miRs) playing a crucial role in drug resistance, the mechanisms comprising miR-519d-3p’s role in CRC drug resistance have not been fully understood. Therefore, the present study aimed to investigate the biological function of miR-519d-3p in the chemosensitivity of CRC cells to 5-Fluorouracil (5-FU). Methods: CRC cells were treated with 5-FU and transfected. Cellular proliferation, invasion, and apoptosis were evaluated. The relationship between miR-519d-3p and 6-Phosphofructokinase-2/Frucose-2, 6-Biphosphatase-3 (PFKFB3) was analyzed, and their interaction in CRC was further investigated. In vivo tumor experiments were conducted to investigate the function of miR-519d-3p and 5-FU in CRC. Results: As determined, CRC cells overexpressing miR-519d-3p were more sensitive to 5-FU in vitro, as miR-519d-3p inhibits proliferation and invasion and stimulates apoptosis. miR-519d-3p directly targeted PFKFB3. In CRC cells, PFKFB3 overexpression rescued miR-519d-3p-induced 5-FU toxicity. In vivo results showed that mice co-treated with miR-519d-3p mimics and 5-FU showed higher antitumor activity. Conclusion: Overall, it may be possible to improve 5-FU chemosensitivity of CRC cells by targeting miR-519d-3p and PFKFB3.

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ABSTRACT Objective: To provide a protocol for the diagnosis and management of Acute Abnormal Uterine Bleeding (AUB) during menacme, addressing common causes, clinical evaluation, and treatment options. Methods: A review of current evidence and guidelines was performed to create a structured approach for healthcare professionals. Results: Acute AUB, defined as excessive uterine bleeding unrelated to pregnancy, requires immediate intervention. Causes vary by age and include coagulopathies, anovulation, and structural anomalies. Clinical stability, lab workups, and imaging are pivotal in guiding management. Initial treatment focuses on hemodynamic stabilization followed by medical therapies such as antifibrinolytics, hormonal agents, or surgical intervention when necessary. Conclusion: Early intervention in AUB ensures optimal outcomes, reduces complications, and allows transition to maintenance therapy to prevent recurrence.

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ABSTRACT Background: This study aimed to assess the predictive value of 7 routinely available inflammation biomarkers for stroke and all-cause mortality in 229 non-valvular AF patients. Methods and results: C-reactive protein, Albumin (ALB), d-dimer, fibrinogen, the number of platelets, lymphocytes, monocyte and neutrophils were measured. The Multivariable Cox proportional hazard model was used to assess the predictive value of the inflammation biomarkers for stroke and all-cause mortality, the c-statistic, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI) were calculated. Lymphocyte Monocyte Ratio (LMR) was the most informative biomarker for predicting stroke, and adding LMR to the CHA2DS2-VASc score did not improve its predictive ability for stroke, but it did improve its reclassification ability. Similar results were observed when comparing LMR+ CHA2DS2-VASc score with the ABC stroke score. For all-cause mortality, a Systemic Inflammation Score (SIS) score was calculated using ALB, fibrinogen and LMR, and adding SIS to the CHA2DS2-VASc score showed a significant improvement in its predictive ability and reclassification ability. There were no significant differences in predictive and reclassification ability for all-cause mortality between SIS+CHA2DS2-VASc score and ABC death score. Conclusions: Adding routinely available inflammatory biomarkers to the CHA2DS2-VASc score increased its ability to predict all-cause mortality, suggesting this cost-effective biomarker strategy may help to improve decision support in AF.

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ABSTRACT Background: Acute Obstructive Septic Cholangitis (AOSC) is a serious infectious disease of the biliary system. It is prone to develop into septic shock without prompt management. Methods: Bile was collected from 71 AOSC patients (45 AOSC without septic shock, 26 AOSC with septic shock) during biliary drainage and on days 1 and 3 postoperatively. The levels of High Mobility Group Protein 1 (HMGB1), Interleukin (IL)-1, IL-6, and Tumor Necrosis Factor alpha (TNF-α) were measured. The differences in the levels of biliary factors and their correlation with clinical biochemical indicators were assessed in the two groups. Results: HMGB1 gradually decreased in both groups in the postoperative period. Intraoperative levels of biliary HMGB1 were significantly higher in patients with AOSC with septic shock. TNF-α and HMGB1 decreased slowly in patients with AOSC with septic shock on postoperative days 1 and 3, and the levels of the factors decreased less. Biliary HMGB1 levels were negatively correlated with white blood cell count and positively correlated with blood urea nitrogen, blood creatinine, procalcitonin, and C-reactive protein. A bile HMGB1 level of 1108.3 pg/mL was the cut-off value to differentiate patients with AOSC with or without septic shock. Conclusion: Biliary HMGB1 levels are elevated in patients with AOSC with septic shock and decrease slowly in the postoperative period. This suggests that HMGB1 is of considerable importance as a potential therapeutic target in the pathogenesis of septic shock in AOSC patients.

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ABSTRACT Background: Uterine fibroids affect maternal and neonatal outcomes adversely. Pregnancy-Associated Plasma Protein-A (PAPP-A) and Uterine Artery Doppler (UAD) are used in the first and second trimesters to predict maternal and neonatal outcomes, including maternal preeclampsia, Small-for-Gestational-Age (SGA), and Low Birth Weight (LBW) babies. Methods: A retrospective review of medical records over 8-months was carried out for 60-patients who presented to the antenatal outpatient clinic. Inclusion criteria were the identification of fibroids in the first-trimester scan, PAPP-A blood test performed at the first visit, and UAD recorded at 20-weeks scan. Demographic characteristics, clinical parameters, pregnancy-related complications, and obstetric outcomes were extracted for data collection. Data analysis was performed to determine correlations between UAD parameters and PAPP-A levels and fibroid measurements for different fibroid types, and to determine the effect of fibroid presence on actual and estimated fibroid weight. Findings: Of 60 included patients, the mean age of patients was 35.8 ± 4.8 years, and each pregnant woman had an average of 2.9 ± 1.7 fibroids, with the majority (73 %) being large (> 5 cm). No complications, such as gestational hypertension, gestational diabetes, preeclampsia, abruption, and preterm birth were reported; only 6 (10 %) of women were sonographically diagnosed with SGA babies, while 2 (3.3 %) babies were LBW. UAD parameters and PAPP-A levels had no significant association with fibroid size (p > 0.05). Conclusion: There is a possible role of UAD and PAPP-A in determining pregnancy outcomes in the presence of fibroids, which needs to be explored by prospective studies.

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Abstract Objective Medical education is undergoing a profound transformation due to technological advancements. Integrating cutting-edge tools like virtual environments and computer-based simulators heralds a new era in teaching methodologies. The objective of the study is to analyze the performance and satisfaction levels of residents undergoing basic surgical skills training using virtual reality. Methods The authors recruited residents from the first year in general surgery and allocated them randomly into three groups: a) Text; b) Practice and c) Virtual reality. Initially, the residents completed a pretest for an evaluation and then they were trained according to the group they were assigned to. All the residents performed a 30-minute training session. After that, they took a posttest. Both tests were composed of multiple-choice ten questions. At the end of this study, the authors determined the score by calculating the delta of the performance (Δ = posttest -pretest). After the training, all the participants filled in a five-question satisfaction questionnaire. Results Regarding the difference between the pretest and post-test, there was no difference between groups. Only one participant (1/8) showed nausea in the virtual groups. The recommendation and satisfaction after the task were higher in the Virtual reality group compared to the Text group. There was an association between satisfaction after the exercises (VR) and recommendation score. Conclusions Virtual reality is safe and non-inferior to traditional surgical instrumentation training. This tool might be a practical and attractive alternative to the traditional instrumentation classes.

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Abstract Objective Isometric exercise can be an alternative approach to lowering blood pressure in individuals with hypertension. However, it is uncertain whether the muscle mass involved can influence Post-Exercise Hypotension (PEH). Thus, the authors evaluate the acute effect of an isometric exercise session with a Small Muscle Mass (SMM) and a Large Muscle Mass (LMM) on Systolic (SBP) and Diastolic (DBP) blood pressure in individuals with hypertension. Method Randomized clinical trial with 36 volunteers aged 40‒70y with hypertension allocated into (n = 12/group): control group (no exercise), SMM group (bilateral isometric handgrip contractions using a hydraulic handheld dynamometer), and LMM group (bilateral isometric full knee extension on a leg extension machine). Both exercise interventions consisted of 4 × 2 min of bilateral contraction at 30 % of the individual's maximum capacity. The authors used 24-hour Ambulatory Blood Pressure Monitoring (ABPM) after the interventions. One-way ANOVA or Generalized Estimation Equations (GEE) were used to test for potential differences (p < 0.05). Results The authors found no increase in SBP/DBP immediately after the interventions. However, 24 h ABPM revealed lower SBP post-intervention in the SMM group (Δ-4.1 mmHg; p = 0.044) and the LMM group (Δ-5.6 mmHg; p = 0.040) compared to the control group, with no difference between these groups. DBP did not change over a period of 24 h ABPM. Conclusions In conclusion, isometric exercise-induced PEH assessed by 24 h ABPM regardless of the muscle mass involved. This study shows that both interventions may contribute to lowering blood pressure in individuals with hypertension. Trial registration: www.clinicaltrials.gov; ID NCT03982758.

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Abstract Objective This study aimed to determine the normal range of fetal weight by ultrasound in pregnant women followed at the Obstetric Clinic of the Hospital das Clínicas of the Faculty of Medicine, University of São Paulo. Methods This retrospective cohort study included singleton pregnant women without associated maternal diseases, at 15-41 weeks of gestation, who underwent their last ultrasound up to 7 days before birth. Fetal parameters analyzed for the normal range were biparietal diameter, femur length, head and abdominal circumference. 3rd, 10th, 50th, 90th, and 97th weight percentiles were determined for each gestational age. Newborns were classified by birth weight as Small (SGA), Appropriate (AGA), or Large (LGA) for gestational age. Results Among 837 women admitted without maternal diseases, 136 were included and 379 examinations performed at 15-41 weeks of gestation. Multiple linear regression models were generated to develop the normal range of fetal weight. Three equations were selected, and six normal ranges were created considering the total population and stratified by fetal sex. Weight estimates were calculated for the 3rd, 10th, 50th, 90th, and 97th percentiles for each gestational age. Among the 136 newborns, 107 (78.7 %) were classified as AGA, 23 (16.9 %) as SGA, and 6 (4.4 %) as LGA. Conclusion The normal range of the fetal weight determined by ultrasound in this population showed a good correlation with gestational age, enabling the fetal weight gain pattern evaluation. The equation based on four parameters, including days before birth, presented the lowest percentage error variation to estimate the normal range.

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Abstract Objective To identify clinical and laboratory risk factors for Pulmonary Arterial Hypertension (PAH) in Idiopathic-Inflammatory-Myopathy (IIM) patients as well as construct a predicting model for PAH. Methods An IIM cohort in southeastern China was established, including 504 adult IIM patients who met the inclusion and exclusion criteria, and were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU) from January 1st, 2018, to April 30st 2022. Serum cytokine profiles, myositis-specific antibodies as well as other factors of patients who met the inclusion and exclusion criteria were collected and analyzed. Results Of the 504 adult IIM patients, 25 IIM patients developed PAH and 48.0 % of them deceased within six months. IIM patients complicated with PAH were found to suffer from worse outcome (p < 0.001). After multivariate logistic regression analysis, age (p < 0.001), bacterial infection (p = 0.005), MYOACT score (p = 0.009), Interleukin (IL)-17A (p = 0.017), anti-SRP antibody (p = 0.011) and steroid monotherapy (p = 0.001) were identified as factors significantly associated with PAH in IIM patients. A “BAIMS” model was constructed by including the above six items to predict PAH with a cut-off value of ≥ 3 and an Area Under the Curve (AUC) of 0.877. Conclusion PAH is a rare but potentially fatal complication in IIM patients. Aging, complication of bacterial infection, elevated disease activity, increased serum IL-17A level, positivity of anti-SRP antibody and steroid monotherapy were significantly correlated with development of PAH in IIM patients. In addition, the BAIMS model was found valuable in prediction and early-identification of PAH in IIM patients.

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Abstract Background In transplantation, sex-mismatched procedures correlate with poorer outcomes. Previous research has indicated that females respond worst to Brain Death (BD) and that organ damage varies with the speed of BD induction. The authors aimed to investigate the effects of slow BD-induction on lung and kidney responses in male and female rats. Methods Males and female rats were subjected to slow induction of BD and kept for 4h. Blood gas samples were taken at 0 h and 4h. At 4 h, blood, urine and tissue samples were collected. IL-1β was measured in plasma, lung homogenate and lung culture. IL-6 was quantified in plasma, lung culture, and kidney homogenate. Leukocyte infiltration/activation was evaluated. Biochemical analyses of creatinine were performed in the plasma. Naïve animals were used as controls. Results Males presented reduced testosterone levels after 4h. Females presented reduced progesterone, whereas estradiol remained similar at 0 h and 4h. Compared with Naive, BD-groups presented increased plasma IL-1β and IL-6. Males and females presented reduced pO2 after BD, with females presenting even lower values at 4h. In lung tissue, males presented increased expression of IL-1β, whereas IL-1β was elevated in females in lung culture. Females presented increased cell infiltration/activation. In the kidney, males presented increased plasma creatinine, increased expression of caspase-3, and increased leukocyte migration to renal tissue than females. Conclusions The authors observed an organ and sex-dependent response to the slow-induction of BD. These results suggest that management strategies should consider the sex of the donor to achieve the best treatment, improving graft quality.

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Abstract Background Myocardial fibrosis contributes to LV mechanical dyssynchrony and fibroblast activation protein is considered as a specific biomarker related to tissue remodeling. The authors aimed to explore the relationship between LVMD and myocardial fibrosis, and patterns of LV fibrosis distribution in CAD and Degenerative Mitral Valve Regurgitant (DMVR) participants by the technique of 18F-AlF-FAPI PET/MR. Methods 37 CAD and DMVR participants with LVMD and normal ones underwent cardiac PET/MR imaging, the correlations between SUVmean of FAPI-uptakes and score/percentage of LV wall thickening, peak myocardial strains, and displacements were analyzed in PET/MR images, and ejection fractions and function parameters of mitral valve were compared. Results There was inverse correlation between SUVmean and score/percentage of LV wall thickening, peak circumferential and short-axial radial myocardial strains, and global peak myocardial strains and ejection fractions showed a decrease significantly in participants with heart diseases. In CAD participants, FAPI was distributed in the ischemic coronary arteries regions. Functions of myocardium in LAD and RCA regions were sensitive to fibrosis, however, those in LCX regions were resistant to fibrosis. In DMVR participants, high uptakes of FAPI were the locations of the valve annulus and papillary muscles, and SUVmean in the basal inferospetal/basal inferior segments were a positive correlation with function parameters of the mitral valve. Conclusion Uptake of 18F-AlF-FAPI in the myocardium could detect fibrosis and predict LVMD in CAD and DMVR participants. Moreover, there were different distributions of FAPI-uptake in those participants. In DMVR participants, SUVmean in the basal inferospetal/basal inferior segments could assess dysfunction of the mitral valve.

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Abstract Within the intricate tapestry of the global SARS-CoV-2 pandemic, this study delves into the intricate interplay of clinical data to elucidate prognostic factors associated with complications in patients concomitantly afflicted with hematological disorders and SARS-CoV-2. An exhaustive analysis of 71 individuals, spanning the period from November 2022 to March 2023, aims to unveil distinctive clinical characteristics and explicate the nuanced determinants steering the trajectory of the disease. The updated findings reveal a multi-faceted correlation, underscoring the complex interplay of clinical parameters. Among individuals with hematological disorders, anomalously elevated ferritin levels are closely associated with the development of SARS-CoV-2 pneumonia, while interferon-γ is intricately linked to the severity of SARS-CoV-2. Conversely, elevated ferritin levels, increased D-dimer and fibrin degradation products, along with significantly elevated iron levels, manifest a significant association with patient mortality. Intriguingly, those in patients in complete hematologic remission confront an augmented risk of developing SARS-CoV-2 pneumonia, while those abstaining from anti-tumor treatments exhibit mitigated case severity. This study unveils the intricate interplay of clinical factors impacting the prognosis of SARS-CoV-2 complications in individuals with hematological disorders. The cognizance of aberrant interferon-γ activation and nuanced associations with ferritin, iron levels, and coagulation markers contributes to a more holistic comprehension of the prognostic landscape.

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Abstract Introduction Renal Ischemia-Reperfusion Injury (RIRI) often arises due to heightened oxidative stress, rendering it a central focus of research. Sestrin2 plays a pivotal role in regulating oxidative stress; nevertheless, its impact on the renoprotective properties of Eugenol (EU) during RIRI warrants further investigation. Methods Mice and TCMK-1 cells were categorically assigned into six groups: Sham/Control, Ischemia-Reperfusion (IR)/HR (Hypoxia-Reoxygenation), IR/HR+EU, Sham/Control+Sestrin2-KO, IR/HR+Sestrin2-KO, and IR/HR+EU+Sestrin2-KO. The effects of EU and the involvement of Sestrin2 in RIRI/HR were evaluated using Urea Nitrogen (BUN), Creatinine (Scr), Superoxide Dismutase (SOD), Glutathione (GSH), Catalase (CAT), and Malondialdehyde (MDA) assay kits; western blotting; cell viability assays; HE-staining; and Reactive Oxygen Species (ROS) detection. Results Following RIRI/HR, a marked deterioration in kidney function and a significant surge in oxidative stress levels were observed. However, EU treatment ameliorated renal injury and inhibited oxidative stress. Additionally, EU upregulated Sestrin2 expression, and the renoprotective effects of EU were reversed upon Sestrin2 knockdown. Conclusion The present study posits that EU effectively mitigates RIRI/HRI (Hypoxia-Reoxygenation Injury), and its mechanism of renal protection potentially involves the upregulation of Sestrin2, coupled with the inhibition of oxidative and Endoplasmic Reticulum Stress (ERS).

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Abstract Background A 2 mm-thick dermal allograft and autologous Long Head of the Biceps Tendon (LHBT) Superior Capsule Reconstruction (SCR) could provide improved clinical and radiographic outcomes for posterosuperior Massive Irreparable Rotator Cuff Tears (MIRCTs). Methods A retrospective study was conducted between April 2019 and October 2021. The LHBT was rerouted 5 mm posteriorly to the bicipital groove, and a 2 mm-thcick dermal allograft was used to cover the rerouted LHBT. Clinical assessment included Constant-Murley Shoulder score (CMS), American Shoulder and Elbow Surgeons (ASES) score, Subjective Shoulder Value (SSV), Visual Analog Scale (VAS) pain scores, and active ROM measurements. The radiological assessment included Acromiohumeral Distance (AHD), Superior Capsular Distance (SCD), muscle Fatty Infiltration (FI), and follow-up SCR integrity using ultrasound two years after surgery. Results 25 patients (7 male, 18 female) were included with a mean age of 64.2 ± 6.9 years. Active ROM, AHD, and SCD did not change significantly after the surgery. Patients' VAS (8.3 ± 0.7 to 1.3 ± 0.6, p < 0.001), SSV (22.4 ± 8.6 to 77.6 ± 12.7, p < 0.001), CMS (36.2 ± 6.8 to 79.9 ± 8.4, p < 0.001), and ASES (37.2 ± 10.0 to 80.5 ± 5.7, p < 0.001) improved significantly at final follow-up. The ultrasound examination of all patients demonstrated a healed dermal allograft on the supraspinatus footprint. One patient (4 %) had a postoperative trauma causing irreparable subscapularis tear, leading to reverse total shoulder arthroplasty during revision surgery. Conclusions The combined SCR technique using a 2 mm dermal allograft and autologous LHBT for posterosuperior MIRCTs significantly improved the patient-reported outcomes.

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Abstract Objective To explore the role of hsa_circ_0095812 (circLRRC4C) in periodontitis and its mechanism with miR-485-3p and Thrombospondin-1 (THBS1). Methods Periodontal tissues were collected from periodontitis patients. Periodontal Ligament Cells (PDLCs) were stimulated with Lipopolysaccharide (LPS) and transfected. Cell viability, inflammation, apoptosis, and pyroptosis were analyzed. A mouse model of periodontitis was constructed and injected with a lentiviral plasmid vector targeting circLRRC4C. Immunohistochemistry was performed on the periodontal tissue of model mice. The relevant expression level of genes was measured via real-time reverse transcriptase-polymerase chain reaction or Western blot. The relationship between circLRRC4C and THBS1 with miR-485-3p was analyzed. Results CircLRRC4C was highly expressed in periodontitis tissues of patients and LPS-treated PDLCs. Downregulating circLRRC4C attenuated LPS-induced PDLC inflammation, apoptosis and pyroptosis and recovered cellular viability. CircLRRC4C acted as a sponge for miR-485-3p. CircLRRC4C affected LPS-induced PDLC apoptosis, pyroptosis and inflammation by regulating miR-485-3p. THBS1 was the target gene of miR-485-3p. Inhibition of THBS1 effectively improved LPS-induced periodontitis. CircLRRC4C aggravated LPS-induced PDLC apoptosis, pyroptosis and inflammation by regulating the miR-485-3p/THBS1 axis. Suppressing circLRRC4C effectively improved periodontitis in mice. Conclusion CircLRRC4C induces periodontitis progression by adsorbing miR-485-3p-mediated THBS1 expression.

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Abstract Objective p53 is a key tumor suppressor, aCnd loss of p53 function promotes the progression of many cancers. Helicobacter Pylori (HP) is mainly involved in the progression of gastric carcinoma, but its role in Oral Squamous Cell Carcinoma (OSCC) is controversial. The primary objectives of this study were to investigate the expression levels of p53 in OSCC tissues and to examine the serum levels of CagA in OSCC patients. Additionally, the authors aimed to explore the potential association between p53 expression and CagA levels in OSCC. Method A total of 65 patients diagnosed with OSCC and 42 healthy volunteers were recruited in this study. The clinical pathological parameters of all patients were collected. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression of p53 in tissues. Receiver Operating Characteristics Curve (ROC) analysis was used to assess the sensitivity of p53 for the diagnosis of OSCC. The concentration of Cytotoxin-Associated gene A (CagA) in serum was assessed by enzyme-linked immuno sorbent assay. Results The results indicated that the p53 expression in oral mucosal tissues was downregulated while the concentration of CagA in serum was increased in OSCC patients. Besides, p53 expression was correlated with tumor stage. OSCC patients showed a higher HP positive rate than in healthy people. Conclusions In conclusion, this study demonstrated that decreased p53 expression and elevated serum CagA levels might be correlated with OSCC progression and diagnosis.

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Abstract Introduction Leukoreduction is performed to decrease the occurrence of adverse effects of transfusion, and can be performed by pre-storage (bench or in-line) or post-storage filtration (bedside) moment. The authors verified the effect of the leukoreduction filtration moment of Red Blood Cell (RBC) and Platelet Concentrate (PC) on the occurrence of Adverse Transfusion Reactions (ATRs), the presence of Healthcare-Associated Infections (HAIs), Length of Hospital Stay (LOS), and hospital death. Methods Retrospective cohort conducted at the Hospital das Clínicas of the Medicine Faculty of the University of São Paulo, and at the Fundação Pró-Sangue Hemocentro in São Paulo, Brazil. Adult patients, hospitalized for >24 hours, who received leukoreduced RBC and/or PC transfusion between 2017‒2020 were included. The generalized mixed effects model and the Wald test were applied in the analysis with a significance level of 5 %. Results The authors evaluated 3668 patients who received 23,782 transfusions and we found no evidence of a leukoreduction filtration moment effect for ATR (p = 0.991) or HAI (p = 0.982), regardless of the transfused blood component. Meanwhile, the leukoreduction filtration moment had an effect (p < 0.001) on LOS, depending on the blood component transfused (p = 0.023), with pre-storage RBC filtration showing better performance, while in-line filtration stood out for PC. Both the leukoreduction filtration moment and the blood component (p = 0.041) influenced hospital death, with emphasis on the protective effect of bench RBC filtration and pre-storage PC filtration. Conclusion The leukoreduction filtration moment associated with the blood component had an effect on the LOS and hospital death of patients undergoing transfusion.

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ABSTRACT Introduction Retinoblastoma-Binding Protein 4 (RBBP4), belonging to the WD-40 family, is an important member of the Polycomb Repressor Complex 2 (PRC2), the Nucleosome Remodeling and Deacetylation complex (NuRD), and is involved in chromatin remodeling, histone deacetylation, and H3K27 methylation. Methods The effects of cisplatin treatment on cell viability were evaluated using the MTT assay. Western blotting was employed to analyze protein expression, and RNA interference-mediated knockdown of RBBP4 and cyclin D1 was conducted using Lipofectamine 2000. The formation of colonies was evaluated following a 14-day cisplatin treatment period. Cisplatin uptake was quantified by atomic absorption spectrophotometry. RNA sequencing was conducted on total RNA extracted from cells, and lentiviral vectors were employed for gene overexpression, followed by puromycin selection. Immunohistochemistry was performed on tissue microarrays of lung and cervical adenocarcinoma in order to evaluate RBBP4 expression. Results In this study, cisplatin was found to induce RBBP4 expression in human lung cancer A549 cells, and RBBP4 expression in cisplatin-resistant A549/DDP cells was significantly higher than in A549 cells. Downregulating RBBP4 expression by small interfering RNA significantly increased the sensitivity of A549 and A549/DDP cells to cisplatin. Conversely, lentiviral-mediated RBBP4 overexpression reduced sensitivity to cisplatin. Mechanistic studies showed that downregulated RBBP4 increased cell sensitivity to cisplatin mainly by inhibiting cyclinD1 expression, and lentiviral-mediated cyclinD1 caused the opposite effects. These same results were verified in human HeLa cells and in cisplatin-resistant HeLa/DDP cells. Discussion This study showed that RBBP4 regulates the sensitivity of tumor cells to cisplatin and is a potential target for reversing cisplatin resistance in tumor cells.

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Abstract Objective To provide an overview of the activities and impact of an Evidence-Based Care Program (EBCP) on professionals’ decision-making in a large hospital located in São Paulo, Brazil. Methods Retrospective descriptive analysis of a hospital EBCP's database (covering a 40-month period), involving data from the studies conducted and an online feedback survey. Results Since its inception, the EBCP performed 95 scientific technical reports, including 55 Rapid Systematic Reviews (RSR) and 40 Literature Reviews (LR). The authors identified 21 review topics, with the 3 most common being inpatients (n = 20), oncology (n = 11), and surgical procedure (n = 9). The 3 most common technologies assessed were medical devices (n = 28), drugs (n = 27), and scale/questionnaire (n = 16). Studies were mainly used to update policy or procedure (n = 59), support scientific research (n = 10), support clinical program development (n = 8), provide clinical guidance (n = 7), or as a communication tool (n = 5). Among the requestors who responded to the feedback survey (76/95), 97 % agreed or strongly agreed that they were satisfied with the review delivered, and 100 % indicated that they likely would request a review in the future and would indicate the EBCP to a coworker. Among the RSR responders (51/55), 94 % agreed or strongly agreed that the EBCP work informed their project or final decision, and 32 % reported that the result presented changed their perspective about the technology assessed. Conclusion Employing evidence-based methodology, the program provided timely and pertinent evidence for local decision-making. Health professionals who utilized the EBPC expressed high satisfaction with the process and reported a positive shift in their decision-making.

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Abstract Background Gastric Cancer (GC) remains a leading global cause of cancer mortality, underscoring the urgent need for advanced prognostic tools. This study aimed to construct and evaluate a prognostic risk signature based on Supramolecular Polymer-Related Genes (SPRGs) in gastric cancer. Methods The authors downloaded data from TCGA-STAD, GEO, and CCLE databases for patients with GC and validation cohorts. Through consensus clustering, Cox proportional hazards models, LASSO Cox regression, and nomogram development, the authors identified and constructed a GC Prognostic risk Index (SPI). Additionally, the authors conducted drug sensitivity analysis and immune landscape assessment. Functional evaluations were conducted through colony formation, transwell invasion, and wound healing assays. Results The authors identified that 182 SPRGs were significantly upregulated and 226 were downregulated in gastric cancer. Consensus clustering revealed two molecular subtypes, with cluster 1 having significantly lower overall survival compared to cluster 2. SPI effectively distinguished high-risk and low-risk patients across all cohorts. Furthermore, SPI was associated with tumor stage, lymph node metastasis, and tumor size, and could predict drug sensitivity in GC patients. Immune landscape analysis showed higher infiltration of naïve B cells, M2 macrophages, and activated NK cells in high-SPI patients. A nomogram model for GC prognosis using SPI and patient age was developed. KLC1 knockdown significantly suppressed GC cell proliferation, while markedly attenuating metastatic potential and invasion capacity. Conclusion This study constructed a prognostic risk signature based on SPRGs in gastric cancer, which is closely related to clinical pathological features, drug sensitivity, and immune landscape, providing new insights for personalized treatment.

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Abstract Introduction Brugada Syndrome (BrS) typically manifests with a dynamic type 1 Brugada pattern (Br1ECGp) that depends on the dominance of the sympathetic or parasympathetic nervous system. This pattern is more prominent during activities that stimulate the vagus nerve, such as sleeping and after meals. By conducting the tilt table test and adding high precordial leads to the standard protocol, it is possible to provoke sympathetic or parasympathetic responses, providing valuable information. Materials and methods This was an observational, cross-sectional and hypothesis-generating pilot study. The tilt table test was performed with high precordial leads on three Brugada patients to assess the Br1ECGp during the test. The ECG features were continuously recorded to analyze variations during all phases of the test. Results The first patient exhibited a significant Br1ECGp that disappeared during the upward phase of the tilt table test and reappeared during the recovery phase. The second patient had a Br1ECGp in three leads that persisted during both the upward and recovery phases of the tilt table test. The third patient displayed a Br1ECGp in three leads, which was maintained during the upward phase in two leads and recovered during the recovery phase. The third patient was the only one to experience cardioinhibitory syncope. Conclusion This study provided insights into the dynamics of the Br1ECGp during the tilt table test when enhanced by high precordial leads. It reaffirmed that the Brugada ECG pattern is influenced by sympathetic or parasympathetic dominance.

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Abstract Background To investigate the combined effect of transperineal ultrasound and Shear Wave Elastography (SWE) in the evaluation and monitoring of pelvic floor functions after total hysterectomy. Methods Fifty-two women who planned to undergo total hysterectomy from January 2019 to December 2022 in Nantong Third People's Hospital were selected, and the pelvic floor functions were assessed using transperineal ultrasound combined with SWE. The dynamic alterations in pelvic floor functions at different time points were compared after hysterectomy. The differences in pelvic floor parameters were compared between Transabdominal Total Hysterectomy (TAH) and Laparoscopic Total Hysterectomy (LTH). Results The Posterior Urethravesical Angle at rest and Valsalve maneuver (R-PUA, V-PUA), antero-posterior diameter of the hiatus at rest and Valsalve maneuver (R-HAPD, V-HAPD), and elastic modulus of left and right puborectalis at rest (R-L-PRE, R-R-PRE), the Urethral Rotation Angle (URA)were obviously higher at 3 mon after surgery than before surgery and at 1-mon after surgery; the bladder neck-symphyseal distance at rest and Valsalve maneuver (R-BSD,V-BSD), and the difference in elasticity between the left and right puborectalis muscles (L-∆E, R-∆E) were markedly lower at 3 mon than before surgery and at 1 mon after surgery; V-BSD, L-∆E, R-∆E were obviously decreased and the Bladder Neck Descen (BND), URA, V-PUA were obviously increased in the TAH group in comparison with the LTH group. Conclusion Pelvic floor functions start to be weak at 3 months after total hysterectomy. TAH causes more significant damage to the structures and functions of the pelvic floor.

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Abstract Lower eyelid malposition, a commonly encountered eyelid disorder, is often linked to discomfort, visual disturbances, and cosmetic concerns. Various treatment modalities have been employed to address these conditions, but their effectiveness and safety remain subjects of debate. This systematic review, aiming to compare and evaluate these treatments, produced a comprehensive analysis of diverse approaches to managing lower eyelid malposition. The search encompassed electronic databases, clinical trial registries, and relevant journals from inception to September 2023. Fifteen studies meeting the inclusion criteria, involving 709 patients (855 eyelids), were reviewed, comprising 12 randomized controlled trials and 3 ongoing trials. We assessed the quality of each included study using the Cochrane Risk-of-Bias tool for randomized trials (RoB v2). We analyzed success rates, recurrence rates, adverse events, and patient satisfaction. Results revealed that modifications to the conventional Lateral Tarsal Strip exhibited high success rates and low recurrence rates. Other treatments, including Everting Sutures, Retraction Pelication, and Orbicularis Muscle Shortening, showed promise in specific cases. Complications, generally mild and manageable, were reported across all modalities, with patients expressing overall satisfaction. The systematic review highlights the effectiveness and safety of various surgical interventions for lower eyelid malposition, offering durable outcomes and minimal recurrence. Tailoring treatments based on patient characteristics and anatomical variations is crucial. Further research is warranted to refine indications for each treatment option in this evolving field.

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Abstract This mini-review explores the potential of precision medicine and personalized nutrition in addressing health challenges faced by perimenopausal women, focusing on the role of genetic polymorphisms in key metabolic pathways. Specifically focus on the single nucleotide polymorphisms (SNPs) in the COMT, FUT2, and MTHFR genes, which influence neurotransmitter metabolism, gut microbiota composition, and folate homeostasis, respectively. These polymorphisms are critical in modulating hormonal fluctuations, metabolic imbalances, and nutrient absorption during perimenopause. The review highlights the impact of COMT rs4680 on stress response and mood disorders, FUT2 rs602662 and rs601338 on vitamin B12 absorption and cortisol metabolism, and MTHFR rs1801133 and rs1801131 on homocysteine levels and cardiovascular risk. Furthermore, the integration of machine learning in precision medicine is discussed, offering insights into how genetic data can optimize personalized interventions. This approach enables targeted nutritional and therapeutic strategies to mitigate the metabolic and psychological effects of perimenopause. Overall, this review underscores the importance of incorporating genetic testing into preventive care for perimenopausal women to enhance quality of life and promote healthy aging.

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Abstract Introduction Autism Spectrum Disorder (ASD) is a neurodevelopment spectrum characterized by persistent deficits in social communication and interpersonal interaction, along with restricted and repetitive patterns of behavior, interest, or activities. The appropriate screening and diagnosis must be realized to improve the children's prognosis. Moreover, appropriate treatments are necessary to promote better social integration and development. In this scenario, this systematic review aims to evaluate the impacts of behavioral therapies applied in healthcare settings for patients with ASD. Methods This systematic review followed the PRISMA guidelines. The databases MEDLINE, Embase, CENTRAL (Cochrane), and Lilacs were accessed, and gray and manual searches were performed. The search strategy was created with terms referring to autism and behavioral therapy. The studies were assessed qualitatively. Results Randomized clinical trials and observational studies demonstrated improvements in cognitive and verbal components of patients who received behavioral therapies in therapeutic settings. These results indicate a positive impact of both cognitive-behavioral therapy and ESDM on the development of patients’ skills. Among the cognitive-behavioral therapies, the one based on the MASSI protocol did not impact the reduction of anxious symptoms. As for cognitive-behavioral therapy, one study demonstrated that the Behavioral Intervention for Anxiety in Children with Autism (BIACA), when compared to the Coping Cat protocol, improves cognition and reduces anxiety symptoms. Despite these results, further randomized clinical trials comparing behavioral therapies with one another are needed. Conclusion In the context of behavioral therapy within a healthcare setting, the Early Start Denver Model (ESDM) showed improvements in the cognitive, verbal, and social aspects of the evaluated patients. Improvement in scores sometimes is achieved independently of the group and related to the time of interventions.

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Highlights Ethnopharmacological knowledge is passed down through generations by women in the community, who use plants especially for sexual and postpartum care.

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Highlights Knowledge was low mainly about contraceptive methods of high effectiveness. The acceptance of the chosen contraceptive method by deaf women was satisfactory. There are no intervention studies to improve contraceptive use among deaf women.

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Highlights Mitochondria regulate cellular functions, and mtDNA mutations can affect metabolism. mtDNA mutations are promising biomarkers for cancer detection and tumor progression. These mutations might influence therapy response, drug resistance, and patient outcomes. Tools and models advance precision oncology and mitochondrial-targeted treatments.

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Highlights NMES+ can improve the aerobic capacity of individuals in functional decline. NMES+ appears to improve physical functional capacity in general. More RCTs are needed to better evaluate the evidence found.

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ABSTRACT Background: Antidepressant-Induced Sexual Dysfunction (AISD) is a significant public health concern, and pharmacological treatments may offer potential solutions for managing this side effect. This study aims to assess the efficacy of these therapies in treating AISD in women, as well as their impact on improving depressive symptoms. Methods: The authors conducted a search of PubMed, Cochrane, Scopus, Web of Science, Embase, and ClinicalTrials.gov databases up to July 3, 2024, including Randomized Controlled Trials (RCTs) comparing pharmacological treatments with placebo. The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2.0). Data synthesis was performed with RevMan 5.4, and the certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Eleven studies, with 859 women, were included in the review. Two studies were used in the metaanalysis. The participants’ ages ranged from 28 to 48 years. The interventions studied included Aphrodite, bupropion SR, ephedrine, maca root, rosa damascena, saffron, sildenafil, testosterone, and the compound VML-670. Bupropion SR 150 mg/b.i.d. showed improvements in three sexual function domains: desire (1.74 [1.03, 2.44], p = 0.00001), arousal (1.30 [1.16, 1.43], p = 0.00001), and orgasm (1.90 [1.78, 2.02], p = 0.00001) compared to placebo. However, it did not improve depressive symptoms (0.46 [-0.71, 1.63], p = 0.44). The GRADE rating for the evidence quality was low. Conclusions: Bupropion SR 150 mg/b.i.d. is the most effective pharmacological treatment for AISD in women, though the evidence quality is low. Further clinical trials focusing on women with rigorous methodologies are needed to strengthen these findings. PROSPERO registration number: CRD42024496931.

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ABSTRACT Background and aim: Minimally invasive techniques offer alternatives to conventional surgery in the treatment of early-stage colorectal cancer, reducing morbidity. Transanal Endoscopic Microsurgery (TEM) and Transanal Minimally Invasive Surgery (TAMIS) are widely used, while Endoscopic Submucosal Dissection (ESD) is gaining attention for its ability to achieve complete resection with low recurrence rates. This study compares the efficacy and safety of ESD with Transanal Endoscopic Surgery (TES). Methods: The authors performed a systematic review and meta-analysis of comparative studies involving patients with endoscopically resectable rectal lesions. Electronic searches were conducted in MEDLINE, EMBASE, Cochrane, and LILACS. Outcomes included recurrence rate, complete resection, en bloc resection, hospital stay, procedure time, and complication rate. Results: The analysis included ten observational studies and one Randomized Controlled Trial (RCT) involving 1,094 patients. No significant differences were found in terms of recurrence rate, en bloc resection, R0 resection, and complications between techniques. The RCT showed a shorter procedure time in the TES (RD = 16.6; 95 % CI 8.88 to 24.32; p < 0.0001), whereas observational studies found no significant difference. In addition, observational studies found a shorter hospital stay duration in the ESD (MD = −1.22; 95 % CI −2.11 to −0.33; I2 = 82 %; p < 0.007), while the RCT found no difference. Conclusion: ESD and TES are safe and effective for the treatment of early-stage rectal tumors. Rates of local recurrence, block resection, R0 resection, complications, and procedure time were similar. However, the RCT showed a shorter procedure time with TES, while observational studies showed a shorter hospital stay with ESD.

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Abstract Phyllodes Tumor (PT) of the breast is a rare type of fibroepithelial neoplasm, classified into benign, borderline, and malignant subtypes. These tumors are known to be locally aggressive and have an inherent potential for Local Recurrence (LR), even after adequate surgical treatment. Establishing strategies to reduce LR has become increasingly important, as 21 % to 36 % of patients experience disease recurrence despite achieving negative surgical margins. Although surgical resection of the lesion is the gold standard treatment for all subtypes of phyllodes tumors, the ideal extent of the surgical margin remains a topic of debate with no consensus in the literature. Adjuvant radiotherapy is suggested as a tool to improve local control of the disease and reduce the recurrence rate; however, published data on this approach are currently conflicting. In this review paper, the authors will provide a detailed analysis of the current evidence on the diagnosis, treatment, follow-up, outcomes, and future perspectives of phyllodes tumors.

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Abstract A medical error is a preventable adverse effect of medical care. These errors are usually avoidable. They are a vast source of ethical, financial, and even mental problems affecting patients, physicians, and healthcare organizations. The negative impact on patients can be physical, generating sequelae or disability. It could lead to a loss of trust in the patient and his family in the doctor or the hospital where he has been treated. On the other hand, doctors resist disclosing their errors to the patient, fearing lawsuits and financial losses. Disclosure errors are also an imperative moral duty. In this narrative review, the authors discuss obstacles that exist and prevent an adequate open disclosure, including flaws in medical education, and propose ten steps to proceed with an open disclosure if a medical error occurs.

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Abstract Objective This meta-analysis aimed to determine the efficacy of melatonin on mortality in patients with severe-to-critical illness COVID-19. Methods A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized Controlled Trials (RCTs) on the treatment of severe-to-critical COVID-19 with melatonin, compared with placebo or blank, were reviewed. Studies were pooled to Odds Ratios (ORs), with 95 % Confidence Intervals (95 % CIs). Results Three RCTs (enrolling 451 participants) met the inclusion criteria. Melatonin showed a significant effect on in-hospital mortality (OR = 0.19, 95 % CI 0.05 to 0.74; p = 0.02). Conclusions Melatonin significantly reduced in-hospital mortality in patients with severe-to-critical COVID-19. Melatonin should be considered for severe-to-critical COVID-19 patients.

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Abstract Introduction Uterine transplantation is indicated for women with absolute uterine factor infertility, which is usually associated with congenital causes (the most common being Mayer-Rokitansky-Kuster-Hauser syndrome) or acquired via hysterectomy. For these women, uterus transplantation is the only possibility for them to be able to conceive and have a biological child. The aim of this study was to understand the motivations that lead women with absolute uterine factor infertility to wish to undergo a uterus transplant. Methods A systematic literature review was performed in the following databases: Medline (PubMed), Embase, Cochrane (CENTRAL), Scopus, Web of Science, and LILACS. Results 439 articles were identified, and nine studies were finally selected. Uterine transplantation was the preferred choice over adoption and surrogacy in most studies (ranging from 45 % to 97.5 %). The main motivations for this type of transplant include the desire to conceive a pregnancy, the desire to have a genetic child, the desire to have control over pregnancy, the physiological repair of the body, the restoration of femininity, and the desire to contribute to science. Conclusion The motivations for uterus transplantation go far beyond the desire to get pregnant and include personal and unique motivations.