OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

Objective: To systematically evaluate the performance of machine learning (ML) models in predicting non suicidal self injury (NSSI) behavior among adolescents, providing an evidence based foundation for the development of clinically applicable risk assessment tools. Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, CNKI, and Wanfang databases for relevant studies from their inception to July 21, 2025. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to evaluate the methodological quality of the included studies. Stata 18 software was used to calculate the area under the receiver operating characteristic curve (AUC) of the models, and publication bias assessment, sensitivity analysis, and Egger s test were performed. Results: The total of 12 studies (42 prediction models) involving 58 070 adolescents were included. There were 15 machine learning algorithms in total, among which Random Forest, Logistic Regression, XGBoost, and Support Vector Machines were the most frequently utilized. The most common predictors were gender (female), family function, depression, emotion regulation, and age. All 12 included studies exhibited a high risk of bias. The pooled AUC was 0.80 (95% CI =0.78-0.82), although heterogeneity was substantial ( I 2=95.8%, P <0.01). Sensitivity analysis confirmed the robustness of these findings (no overlap in 95% CI ), while Egger s test indicated the presence of publication bias ( P <0.05). Conclusions Machine learning demonstrates potential in the risk prediction of adolescent NSSI, but existing models have a high risk of bias. Future research should focus on improving methodological quality and optimizing model reliability through rigorous external validation.

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Pyroptosis is a kind of programmed cell death,which is not only related to colorectal cancer,bladder cancer,gastric cancer,breast cancer and other tumors,but also related to cervical cancer,ovarian cancer and endometrial cancer.In recent years,the diagnosis and treatment of gynecological tumors have been improved,but their incidence and mortality are still high,which seriously threaten women's health.The current difficulty in treating gynecological tumors is reflected in the chemotherapy resistance of cervical cancer,the difficulty in early detection of ovarian cancer,the rapid progression and easy recurrence of late stage ovarian cancer,and the poor prognosis of late stage endometrial cancer.Therefore,this article reviews the roles of pyroptosis in the occurrence and development of gynecologic tumors,in order to provide clues for early diagnosis and treatment of gynecological tumors.

Objective To provide an efficient,reliable,and easily manageable data center solution for hospitals.Meth-ods Through comparative analysis and empirical research,this study explores how hyper-converged technology can help hospitals optimize resource allocation,improve service quality,and ensure data security.Results Hyper-converged technology demon-strates significant benefits in assisting hospitals to optimize resource allocation,enhance service quality,and guarantee data secur-ity.Conclusion Hyper-converged technology offers distinct advantages in terms of cost,operation and maintenance,and relia-bility,making it a mainstream trend in future hospital data center construction.

Objective To explore the associations of dietary patterns with bone mineral density(BMD)and osteoporosis(OP)in patients with knee osteoarthritis(KOA)in south China,identify the dietary patterns that could reduce the risk of OP,and provide a reference for prevention of OP.Methods Data from 600 KOA patients who were enrolled in the Pearl River Osteoarthritis Cohort(PROC)between April 2020 and April 2024 were extracted,including general characteristics,dietary questionnaire and BMD test.Factor analysis was employed to identify dietary patterns.Scores of dietary pattern were treated as continuous or categorical variables(quartile-based groups).Multivariable linear regression was used to assess associations between scores of dietary pattern and BMD,while the relationships with OP were analysed by binary logistic regression.Results The prevalence of OP in KOA patients was 19.8%.Factor analysis extracted eight dietary patterns:seafood-nuts,livestock-poultry meats,coarse grains-fruits,wheat-eggs,fish-dairy-vegetables,legumes-fruits,rice-wheat flour,and soy-dairy.After adjusting for confounders,it was found that the pattern of coarse grains-fruits was positively correlated with the BMD of left femoral neck and lumbar spine(P<0.01)and the fish-dairy-vegetables pattern was positively correlated with the BMD of lumbar spine(P<0.01).When pattern scores were discretized into quartiles,the legumes-fruits pattern(Q3 vs.Q1)was found in association with a 68.2%reduction in the risk of OP(P<0.05).Conclusion This study has identified that the pattern of legumes-fruits may lower a risk of OP,while the patterns of coarse grains-fruits and fish-dairy-vegetables correlate with higher BMD.The diet patterns are potentially beneficial to prevention of OP.For bone health,a balanced diet rich in legumes,fruits,vegetables,coarse grains,fish,nuts and dairy is recommended.

Objective:To establish an early warning model of oral infection risk in patients with acute leukemia undergoing chemotherapy and to verify its predictive efficacy, so as to provide reference for formulating strategies to prevent oral infections.Methods:A retrospective study was conducted to select 288 patients with acute leukemia undergoing chemotherapy from January 2021 to January 2023 in Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences) as the training set. According to whether they developed oral infection after chemotherapy, they were divided into the infected group and the non-infected group. The risk factors of oral infection in patients with acute leukemia undergoing chemotherapy were investigated, and a risk warning model was established. A total of 246 acute leukemia undergoing chemotherapy patients admitted to the same hospital from February 2023 to February 2024 were selected as the validation set to conduct external verification of the model.Results:The oral infection rate was 19.44% (56/288) in the training set. There were 21 males and 35 females in the infected group (56 cases), with 49 cases<60 years old and 7 cases ≥60 years old. There were 102 males and 130 females in the non infected group (232 cases), with 196 cases<60 years old and 36 cases ≥60 years old. Multivariate analysis showed that neutrophil count <1.5×10 9/L, nutritional risk screening 2002≥3 points, high-dose of methotrexate, antibiotic types ≥3, poor oral self-cleaning habits, oral pH ≤6.5 were the risk factors for oral infection in patients with acute leukemia undergoing chemotherapy ( OR values were 2.716-10.074, all P<0.05). Based on this, the risk early warning model was as follows: Logit ( P)=-5.849+2.310× neutrophil count <1.5×10 9/L+1.363× nutritional risk screening 2002≥3 points +1.150× high-dose methotrexate +1.132× antibiotic types ≥3 + 1.044× oral pH ≤6.5 + 0.999× poor oral self-cleaning habits. The area under receiver operator characteristics curves (ROC) curve of this model Logit ( P) was 0.892, the maximum approximate entry index was 0.653, the sensitivity was 0.804, and the specificity was 0.849. Hosmer-Lemeshow test results indicated that χ2=4.91, P=0.768. For external validation, the goodness of fit test results were χ2=6.47, P=0.595. The area under ROC curve was 0.884, the sensitivity was 0.832, and the specificity was 0.825. Conclusions:The established early warning model of oral infection risk in patients with acute leukemia undergoing chemotherapy has good predictive value, which is helpful for medical staff to conduct early risk assessment of oral infection in such patients, and formulate countermeasures to reduce the incidence and improve the treatment effect of the disease.

Objective:To evaluate the anti-reflux effect of digestive tract reconstruction using esophageal-tubular gastric asymmetric anastomosis after radical resection of esophageal and esophagogastric junction cancer.Methods:The main steps were as follows:(1)oblique incision of the lower esophagus;(2)curved incision of the tubular anterior gastric wall;(3)the lower end of the esophagus was anastomosed to the tubular gastric incision with a 90-degree torsion; (4)The anterior wall of the anastomosis was reinforced with a transverse-inverted suture,the posterior wall with a folded suture,and the corners of the gastric stump were buried with sutures.The anastomosis operation time,postoperative complications and postoperative hospital stay were recorded;the reconstructed structure and anti-reflux effect of the anastomosis were observed by digestive tract radiography,gastroscopy and follow-up investigation.Results:The Department of Gastrointestinal and Thoracic Surgery of Huaian First People's Hospital, affiliated to Nanjing Medical University, treated 5 patients of esophagogastric junction cancer and 20 esophageal cancer cases between August 2022 and November 2024, including 19 men and 6 women, with a mean age of (66.7±7.4) years. The mean anastomosis time was (35.4±5.9) minutes, the intraoperative blood loss was (117.6±33.4) ml and the mean postoperative hospital stay was(16.6±5.2) days, with no complications such as anastomotic leakage and bleeding. Postoperative digestive tract radiography (Trendelenburg position)showed that all the patients had no contrast reflux,gastroscopy showed no signs of reflux esophagitis and bile reflux gastritis, the anastomosis showed an inverted whiskers valve-like structure. The median follow-up time was (16.8±6.3) months, and all patients had no reflux symptoms such as acid reflux and belching,and no acid suppressive medication was needed.Conclusion:The esophageal-tubular gastric asymmetric anastomosis is a safe and effective antireflux reconstruction technique.

Objective To observe the value of T1WI deep learning models for evaluating brain injury of neonatal hyperbilirubinemia(NHB).Methods Totally 106 NHB(defined as newborns with neonatal behavioral neurological assessment≤37,NHB group)and 119 non-NHB newborns(control group)in center A,as well as 34 NHB and 18 non-NHB newborns in center B were collected.ROI was delineated based on bilateral globus pallidus on T1WI.A total of 690 slices were obtained by preprocessing data of center A and then were divided into training set(n=552)and test set(n=138)at a ratio of 8∶2.ResNet18,DenseNet121 and EfficientNetB0 models was established,respectively.External validation was performed based on data of center B.Receiver operating characteristic curves were drawn,area under the curves(AUC)were calculated to evaluate the performance of models for assessing NHB brain injuries compared with traditional visual analysis.Results The AUC of ResNet18 model for evaluating NHB brain injury was 0.910-0.990,significantly higher than that of DenseNet121 model(0.710-0.820)and EfficientNetB0 model(0.640-0.740)(all P＜0.001).The accuracy,sensitivity and precision of ResNet18 model for evaluating NHB brain injury were all higher than those of visual analysis(all P＜0.05),while no significant difference of specificity was found between the above two(P＞0.05).Conclusion T1WI ResNet18 model showed excellent performance and generalization ability for evaluating NHB brain injury.