Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To investigate the influence of serum C-X-C motif chemokine ligand 9 (CXCL9) and C-X3-C motif chemokine ligand 1 (CX3CL1) on the development of preeclampsia in patients with gestational diabetes mellitus (GDM).Methods:A retrospective analysis was conducted on the clinical data of 398 GDM patients admitted to Huangshi Aikang Hospital from January 2021 to August 2024. Based on the occurrence of preeclampsia, patients were divided into the GDM-preeclampsia group (51 cases) and the simple GDM group (347 cases). The baseline data, blood glucose indicators, four lipid items, platelet count (PLT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen, serum creatinine, and 24-hour urinary protein quantification were compared between the two groups. The influencing factors for GDM complicated by preeclampsia were analyzed, and the predictive value of serum CXCL9 and CX3CL1 for the onset of preeclampsia in GDM patients was assessed. Measurement data with a normal distribution were expressed as Mean ± SD, and the t'-test was used for intergroup comparisons when variances were unequal; measurement data with a skewed distribution were expressed as M ( Q1, Q3), and the Wilcoxon rank-sum test was used for intergroup comparisons; counting data were expressed as case (%), and the χ2 test was used for intergroup comparisons. Unconditional logistic regression models were used to analyze the risk factors for preeclampsia in GDM patients. The predictive value of serum CXCL9 and CX3CL1 levels for preeclampsia in GDM patients was analyzed using the receiver operator characteristic (ROC) curve. Results:Pre-pregnancy body mass index, glycated hemoglobin, and 24-hour urinary protein quantification in the GDM-preeclampsia group [(24.50±3.74) kg/m 2, (5.68±0.52)%, 0.42 (0.17, 0.69) g] were all higher than those in the simple GDM group [(22.70±2.97) kg/m 2, (5.42±0.44)%, 0.30 (0.10, 0.44) g], with statistically significant differences between groups (statistic values: t'=3.90, t'=3.85, U=2.70; P values: <0.001, <0.001, 0.007, respectively). Serum CXCL9 levels in the GDM-preeclampsia group [(111.69±36.65) ng/L] were lower than those in the simple GDM group [(200.16±85.57) ng/L], while CX3CL1 levels [(2.22±0.29) μg/L] were higher than those in the simple GDM group [(1.83±0.35) μg/L], with statistically significant differences ( t' values: 7.28 and 7.58, respectively; both P<0.001). Multivariate logistic regression analysis showed that increased CX3CL1 ( OR=1.562, 95% CI: 1.237-1.972), decreased CXCL9 ( OR=0.979, 95% CI: 0.970-0.989), increased pre-pregnancy body mass index ( OR=1.226, 95% CI: 1.060-1.417), and increased glycated hemoglobin ( OR=3.474, 95% CI: 1.192-10.122) were associated with an increased risk of developing preeclampsia in GDM patients ( P values: <0.001, <0.001, 0.006, 0.023, respectively). The ROC curve showed that the area under the curve for serum CXCL9 (sensitivity: 88.24%, specificity: 70.89%) and CX3CL1 (sensitivity: 78.43%, specificity: 69.16%) in predicting preeclampsia in GDM patients were both >0.50 ( P values: 0.015, 0.034, respectively), indicating that both have high predictive efficacy, with CXCL9 being slightly superior to CX3CL1. Conclusion:Decreased serum CXCL9 and increased CX3CL1 are associated with an increased risk of preeclampsia in GDM patients. Both can serve as auxiliary predictive indicators for preeclampsia in GDM patients.

The prevalence of chronic constipation among the elderly is significant, exerting adverse effects on both their physical and mental health.Presently, pharmacological therapy remains the predominant treatment modality for elderly patients with chronic constipation; however, prolonged use can lead to drug dependence, tolerance, and adverse effects.This article systematically reviews non-pharmacological interventions for chronic constipation in elderly patients, both domestically and internationally, aiming to provide a comprehensive reference for clinical practice.

This study examines the progress and application of Artificial Intelligence (AI) in the prevention and control of infectious diseases within Chinese healthcare institutions. It analyzes the difficulties and challenges encountered during implementation to promote the intelligent transformation and upgrading of infectious disease prevention and control. The results indicate that AI technology has made progress in areas such as infectious disease surveillance and early warning, risk assessment and emergency response, screening and detection, image-based diagnosis and analysis, and health management. Nevertheless, significant challenges remain, including limited application depth and breadth, issues with data quality and privacy protection, insufficient technological maturity and interpretability, potential legal risks, and a shortage of interdisciplinary professionals. To advance the application of AI technology in infectious disease prevention and control and support the modernization of China′s relevant systems, recommendations include strengthening policy support, establishing data standards and robust privacy protection mechanisms, increasing R&D investment, refining laws and regulations, and enhancing the training of interdisciplinary talent.