ObjectiveTo establish a new noninvasive， simple， and convenient clinical predictive model by identifying independent predictive factors for rebleeding after endoscopic therapy in cirrhotic patients with esophagogastric variceal bleeding （EGVB）， and to provide a basis for individualized risk assessment and development of clinical intervention strategies. MethodsCirrhotic patients with EGVB who were diagnosed and treated in The First Affiliated Hospital of Xi’an Medical University from September 2018 to October 2023 were enrolled as subjects， and according to whether the patient experienced rebleeding within 1 year after endoscopic therapy， they were divided into rebleeding group with 93 patients and non-rebleeding group with 84 patients. Clinical data were collected and analyzed. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. A Logistic model was established based on the results of the univariate and multivariate analyses， and the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to assess the accuracy of the model. R software was used to visualize the model by plotting a nomogram， and the Bootstrap method was used for internal validation of the model. ResultsThe multivariate analysis showed that red blood cell count （RBC）， cholinesterase （ChE）， alkaline phosphatase （ALP）， albumin （Alb）， thrombin time （TT）， portal vein trunk diameter， sequential therapy， and primary prevention were independent predictive factors for rebleeding. Based on the results of the multivariate analysis， a logistic model was established as logit（P）=-0.805-1.978×（RBC）+0.001×（ChE）-0.020×（ALP）-0.314×（Alb）+0.567×（TT）+0.428×（portal vein trunk diameter）-2.303×［sequential therapy （yes=1， no=0）］-2.368×［primary prevention （yes=1， no=0）］. The logistic model （AUC=0.928， 95% confidence interval ［CI］： 0.893—0.964， P<0.001） had a better performance in predicting rebleeding than MELD score （AUC=0.603， 95%CI： 0.520—0.687， P=0.003）， Child-Pugh class （AUC=0.650， 95%CI： 0.578—0.722， P=0.001）， and FIB-4 index （AUC=0.587， 95%CI： 0.503—0.671， P=0.045）. The model had an optimal cut-off value of 0.607， a sensitivity of 0.817， and a specificity of 0.817. Internal validation confirmed that the model had good predictive performance and accuracy. ConclusionSequential therapy， implementation of primary prevention， an increase in RBC， and an increase in Alb are protective factors against rebleeding， while prolonged TT and widened main portal vein diameter are risk factors. The logistic model based on these independent predictive factors can predict rebleeding and thus holds promise for clinical application.

ObjectiveTo explore the effects of transmembrane protein 16B （TMEM16B） on brain edema and blood-brain barrier after cerebral ischemia-reperfusion injury in rats. MethodsTMEM16B overexpression and knockdown was performed by adeno-associated virus （AAV）， and then adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion （MCAO）. Rats were randomly divided into Sham group， MCAO group， AAV no-load group， TMEM16B overexpression group and TMEM16B knockdown group. Modified neurological severity scores， adhesive removal test and cylinder test were used to evaluate neurologic function. The ultrastructure of ischemic brain tissue was observed by transmission electron microscope. Brain water content was reflected by dry wet weight ratio of brain tissue. The expressions of TMEM16B， aquaporin4 （AQP4）， Claudin5 and zonula occludens-1 （ZO-1） were investigated by immunofluorescence and Western blot. ResultsCompared with the AAV no-load group， the sensory and motor functions of rats in TMEM16B overexpression group were significantly impaired. Mitochondria were swollen； mitochondrial cristae and tight junctions disappeared. The brain water content was higher in overexpression group. The expression of TMEM16B and AQP4 increased while the expression of Claudin5 and ZO-1 decreased （all P<0.05）. Compared with the AAV no-load group， the rats in TMEM16B knockdown group showed some recovery in motor function. The mitochondrial cristae and structure were clear， and the basement membrane was partially blurred. The brain water content was lower in knockdown group. The protein levels of TMEM16B and AQP4 were lower while the levels of Claudin5 and ZO-1 were higher in TMEM16B knockdown group than in AAV no-load group （all P<0.05）. ConclusionAn increase in TMEM16B expression aggravates brain edema and blood-brain barrier damage in rats after cerebral ischemia-reperfusion injury， while a decrease in TMEM16B expression alleviates brain edema and protects the blood-brain barrier.

The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

Traditional four examinations of traditional Chinese medicine （TCM） are based on the symptoms and signs of patients， which are the advantages of TCM but also have shortcomings. Chronic kidney disease has the characteristics of insidiousness， long-term， deficiency and variability during its onset， which are difficult to be intervened in time based on only symptoms， therefore it is necessary to extend the application of the four examinations in the diagnosis and treatment process of chronic kidney disease. Based on the background of the continuous development of TCM syndrome differentiation techniques， this article proposed the extension and application strategies of the traditional four examinations in chronic kidney disease， including the incorporation of microscopic syndrome differentiation to identify the causes of kidney disease and prevent symptom deterioration； the utilization of accurate examination information enhanced by artificial intelligence for controlling development of existing disease； the integration of disease differentiation and syndrome differentiation to summarize clinical rules towards using constant to measure variation； and the establishment of a kidney disease database for the storage of four examinations information to prevent recurrence after recovery. The four above extension and application strategies can be used to achieve the long-term management and treatment effects of timely and early diagnosis， dynamic observation of the condition， accurate application of intervention， and strengthened prognosis assessment in the diagnosis and treatment of chronic kidney disease， and expand the advantages of TCM in the prevention and treatment of chronic kidney disease.

Objective To analyze the clinical features of chronic obstructive pulmonary disease (COPD) patients with heart failure (HF) in Nanjing and explore the influencing factors. Methods A total of 773 COPD inpatients were selected from January 2021 to January 2024 in Nanjing Combined Hospital of Traditional Chinese and Western Medicine, Nanjing Qixia District Hospital, Nanjing Lishui District People's Hospital, Nanjing Pukou District Hospital of Traditional Chinese Medicine and Nanjing First Hospital., and were divided into 2 groups according to the presence or absence of combined HF. The general data and medical records of the two groups were compared, the clinical characteristics of COPD patients with HF were summarized, and the influencing factors of COPD patients with HF were analyzed by multivariate logistic regression. Results Among the 242 patients (31.31%) with COPD had HF, chronic paroxysmal dyspnea was the most common first symptom, 169 patients (69.83%) had left heart failure, 63 patients (30.17%) were diagnosed as right heart failure or global heart failure , 17 patients (7.02%) had myocardial infarction. Multivariate logistic regression analysis showed that the risk of HF was 1.678 times and 1.691times higher in COPD groups ≥ 50 years old and male COPD groups than in < 50 years old and female groups, respectively; the risk of HF was 1.491 times higher in COPD groups engaged in physical work than in physical work groups; the risk of HF was 1.447 times and 1.580 times higher in COPD groups with hypertension and coronary heart disease than in COPD groups without hypertension and coronary heart disease, respectively; the risk of HF was 1.859 times higher in COPD groups smoking>400 vial/year than in COPD groups≤400 vial/ year; the risk of HF was 1.757 times higher in COPD groups with acute exacerbation frequency≥2 times/year than in COPD groups<2 times/year; the above differences were statistically significant (P<0.05). Conclusion Attention should be paid to elderly, male and heavy physical work group of COPD patients. Active treatment of hypertension and coronary heart disease, effective tobacco control and reduction of the frequency of acute exacerbation are effective ways to reduce the risk of HF in COPD patients in Nanjing.

Background High-sensitivity C-reactive protein (hs-CRP) is a sensitive biomarker for cardiovascular disease (CVD) and can independently predict the risk of cardiovascular events. Although the association between per- and polyfluoroalkyl substances (PFAS) exposure and CVD risk has been widely reported, studies on the association between hs-CRP and PFAS remain limited. Objective To investigate the association between PFAS and hs-CRP levels, to provide a scientific basis for early identification and prevention of environment-related cardiovascular events. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018). Based on predefined inclusion and exclusion criteria, a total of 3219 participants were included for subsequent analysis. Five PFAS with detection rates exceeding 90% were selected as exposure factors and log-transformed (lnPFAS) for subsequent analysis, including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA). After selecting potential confounders through a change-in-estimate approach, logistic regression was employed to examine the effects of individual PFAS on serum hs-CRP level. Additionally, quantile g-computation and Bayesian kernel machine regression (BKMR) were applied to assess the combined effects of PFAS mixtures on hs-CRP. Results The study included 3219 participants with a mean age of (50.4±17.6) years, of whom 1554 (48.28%) were male. The median concentrations of the five PFAS compounds were: 1.20 ng·mL⁻¹ (PFHxS), 0.50 ng·mL⁻¹ (PFNA), 1.50 ng·mL⁻¹ (PFOA), 5.20 ng·mL⁻¹ (PFOS), and 0.20 ng·mL⁻¹ (PFDA). The Wilcoxon rank-sum tests revealed statistically significant differences between the elevated serum hs-CRP (≥2 mg·L⁻¹) and normal (<2 mg·L⁻¹) groups for all five PFAS compounds (PFHxS: P=0.005; PFNA: P=0.009; PFOA: P<0.001; PFOS: P<0.001; PFDA: P<0.001). After adjusting for potential confounders, the analysis of individual PFAS exposure demonstrated significant negative associations between serum hs-CRP levels and both ln-PFOS (OR: 0.87; 95%CI: 0.79, 0.96; P=0.0036) and lnPFDA (OR: 0.78; 95%CI: 0.71, 0.86; P < 0.001). The joint effect analysis using quantile g-computation revealed an overall inverse association between PFAS mixtures and hs-CRP, with lnPFDA emerging as a primary contributor; an similar association was observed in males, but not significant in females. Further evaluation through BKMR showed that when PFAS mixture concentrations reached or exceeded P₇₀, their combined effect on hs-CRP became significantly lower than when all PFAS concentrations were at P₅₀, establishing a clear negative dose-response relationship. Conclusion The mixed exposure to PFAS showed a significant negative joint effect on serum hs-CRP levels, with PFDA being the key component contributing to this combined effect. Future prospective cohort studies are warranted to further validate these findings and elucidate the underlying mechanisms involved.

Objective: To investigate the prevalence of hypertension, diabetes and hyperlipidemia among HIV/AIDS patients aged 50 years and above receiving antiretroviral therapy (ART) in Wuxi City, Jiangsu Province, so as to provide insights into the prevention and intervention of chronic diseases for these populations. Methods: The HIV/AIDS patients aged 50 years and above receiving ART were recruited at designated HIV/AIDS medical institutions in Wuxi City using the convenient sampling method from March to June 2024. Demographic information, treatment status and self-reported prevalence of hypertension, diabetes and hyperlipidemia were collected through questionnaire surveys. Factors affecting the prevalence of chronic diseases were analyzed using a multivariable logistic regression model. Results: A total of 830 HIV/AIDS patients receiving ART were surveyed, including 656 males (79.04%) and 375 patients aged 50 to <60 years (45.18%). Among them, 366 patients reported having at least one type of chronic disease, including hypertension, diabetes and hyperlipidemia, with a self-reported prevalence rate of 44.10%. Specifically, 280, 114 and 61 patients reported having hypertension, diabetes and hyperlipidemia, with the self-reported prevalence rates of 33.73%, 13.73% and 7.35%, respectively. Multivariable logistic regression analysis showed that male patients (OR=1.725, 95%CI: 1.187-2.507), those with monthly income less than 3 000 yuan (OR=1.521, 95%CI: 1.122-2.063), those with body mass index of 24 kg/m2 and above (OR=1.577, 95%CI: 1.168-2.130), those who initiated ART at ages of 50 years and above (50 to <60 years, OR=1.535, 95%CI: 1.052-2.238; ≥60 years, OR=3.322, 95%CI: 2.191-5.038), those with ART duration of 10 years and above (OR=2.069, 95%CI: 1.419-3.017), and those who received non-first-line regimens (OR=1.776, 95%CI: 1.304-2.418) had higher risks of developing at least one type of chronic disease, including hypertension, diabetes and hyperlipidemia. Conclusions The self-reported prevalence of at least one type of chronic disease, including hypertension, diabetes and hyperlipidemia among HIV/AIDS patients aged 50 years and above receiving ART in Wuxi City was 44.10%. Gender, monthly income, body mass index and ART status are the main influencing factors for the risk of chronic diseases.

INTRODUCTION: Paediatric sexual assault (SA) victims should be assessed for post-exposure prophylaxis (PEP) to mitigate the risk of sexually transmitted infections (STIs). We describe the clinical characteristics of children and young persons (CYPs) presenting with SA at KK Women's and Children's Hospital in Singapore, viral PEP (human immunodeficiency virus [HIV] and hepatitis B virus [HBV]) prescribing practices, and STI evaluation at follow-up. METHOD: Medical records of CYPs ≤16 years who presented with SA between January 2022 and August 2023 were reviewed, including assault and assailant characteristics, baseline and follow-up STI screening, PEP prescription, adherence and follow-up attendance. CYPs with SA in the preceding 72 hours by HIV-positive or HIV-status unknown assailants with high-risk characteris-tics were eligible for HIV PEP. RESULTS: We analysed 278 CYPs who made 292 SA visits. There were 40 (13.7%) CYPs eligible for HIV PEP, of whom 29 (82.9%) received it. Among those tested at baseline, 9% and 34.9% of CYPs tested positive for Chlamydia trachomatis and Gardnerella vaginalis, respectively. None tested positive for Neisseria gonorrhoeae, Trichomonas vaginalis, HIV, HBV or hepatitis C. Majority of CYPs tested were HBV non-immune (n=167, 67.6%); only 77 (46.1%) received the vaccine. Out of 27 CYPs eligible for HBV PEP with immunoglobulin, only 21 (77.7%) received immunoglobulin. A total of 37 CYPs received HIV PEP, including 8 who were retrospectively deemed ineligible. Only 10 (27%) completed the course. Overall, 153 (57.7%) CYPs attended follow-up, and none seroconverted for HIV or HBV. CONCLUSION We report suboptimal rates of HBV post-exposure vaccination, and low compliance to HIV PEP and follow-up among paediatric SA victims. Factors contri-buting to poor compliance should be examined to optimise care for this vulnerable population.
Humans ; Post-Exposure Prophylaxis/methods* ; Female ; Child ; Adolescent ; Singapore/epidemiology* ; HIV Infections/prevention & control* ; Male ; Sexually Transmitted Diseases/epidemiology* ; Retrospective Studies ; Hepatitis B/prevention & control* ; Follow-Up Studies ; Child, Preschool ; Sex Offenses/statistics & numerical data* ; Child Abuse, Sexual

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL