Noninvasive models for the prediction of liver fibrosis in patients with chronic hepatitis B.

OBJECTIVE: To evaluate the diagnostic accuracy of aspartate aminotransferase(AST)/ alanine transaminase (ALT), AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and gamma-glutamyl transpeptidase to platelet count ratio (GPR) for hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS: A total of 1210 CHB patients who underwent liver biopsy were divided into two groups: patients with no significant fibrosis (control group) and patients with significant fibrosis, and routine laboratory tests were retrospectively included. Logistic regression models were used for the prediction, and the area under the receiver operating characteristic (AUROC) was used to assess the diagnostic accuracy. RESULTS: A total of 631 (52.1%) and 275 (22.7%) patients had significant fibrosis (≥ S2) and advanced fibrosis (≥ S3), respectively. The GPR showed significantly higher diagnostic accuracy than that of APRI, FiB-4, and AST/ALT to predict ≥ S2(significant fibrosis) and ≥ S3 fibrosis(advanced fibrosis), with an AUROC was 0.69 (95%CI: 0.66-0.71) and 0.72 (0.69-0.75), respectively. After stratified by the status of HBeAg ( positive or negative), GPR, APRI, and FiB-4 showed improved predicting performance for significant fibrosis and advanced fibrosis in HBeAg positive patients, with the most significant improvement was shown for GPR in predicting significant fibrosis (AUROC = 0.74, 95%CI: 0.70-0.78). CONCLUSIONS: Among the four noninvasive models, GPR has the best performance in the diagnosis of hepatic fibrosis in CHB patients and is more valuable in HBeAg-positive patients.

SRT1720 inhibits bladder cancer cell progression by impairing autophagic flux.

Bladder cancer (BC) is the most common cancer of the urinary tract, with poor survival, high recurrence rates, and lacking of targeted drugs. In this study, we constructed a library to screen compounds inhibiting bladder cancer cells growth. Among them, SRT1720 was identified to inhibit bladder cancer cell proliferation in vitro and in vivo. SRT1720 treatment also suppressed bladder cancer cells migration, invasion and induced apoptosis. Mechanism studies shown that SRT1720 promoted autophagosomes accumulation by inducing early-stage autophagy but disturbed the late-stage of autophagy by blocking fusion of autophagosomes and lysosomes. SRT1720 appears to induce autophagy related proteins expression and alter autophagy-related proteins acetylation to impede the autophagy flux. LAMP2, an important lysosomal associated membrane protein, may mediate SRT1720-inhibited autophagy flux as SRT1720 treatment significantly deacetylated LAMP2 which may influence its activity. Taken together, our results demonstrated that SRT1720 mediated apoptosis and autophagy flux inhibition may be a novel therapeutic strategy for bladder cancer treatment.

Influence of Gender on Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis.

Background: To assess whether there are differences in common postoperative complications and survival between men and women after transcatheter aortic valve implantation. Methods: We searched the Cochrane Library, PubMed, Embase, and the Web of Science from January 2000 to August 2022. Gender-related articles reporting complications and mortality after transcatheter aortic valve implantation were identified. The primary outcomes were the thirty-day mortality, one-year mortality and perivalvular leakage. The secondary outcomes were conversion to open heart surgery during operation, ejection fraction after operation, reintervention and other common postoperative complications. Data were pooled using the risk ratio or standardized mean difference with 95% confidence interval. Subgroup analysis, meta-regression, sensitivity analysis, egger's test and begg's test were performed. The original study protocol was registered prospectively with PROSPERO (CRD42021245858). Results: There were 24 studies, a total of 92,499 patients, enrolled in our systematic review and meta-analysis, including 43,948 men and 48,551 women. Comprehensive analysis showed significant differences in gender in postoperative complications and survival after transcatheter aortic valve implantation. Men had a significantly higher risk of perivalvular leakage (risk ratio (RR) = 1.42; 95% CI: 1.15 to 1.75; p = 0.001; I 2 = 68%), but lower risk in bleeding (RR = 0.69; 95% CI: 0.61 to 0.79; p < 0.00001; I 2 = 82%), vascular complications (RR = 0.56; 95% CI: 0.52 to 0.61; p < 0.00001; I 2 = 48%), and stroke (RR = 0.86; 95% CI: 0.80 to 0.93; p < 0.00001; I 2 = 12%). The thirty-day mortality of men is slightly lower than that of women (RR = 0.87; 95% CI: 0.81 to 0.93; p = 0.0001; I 2 = 47%), the difference in one-year mortality was also significant (RR = 1.20; 95% CI: 1.08 to 1.33; p = 0.0008; I 2 = 59%). Univariate meta-regression analyses showed that pulmonary hypertension is the major source of heterogeneity in bleeding. Conclusions: Men after transcatheter aortic valve implantation have a lower risk of related postoperative complications, but a higher risk of paravalvular leak and no advantage in medium-term survival.