Objective To study the effect of ursolic acid (UA) intervention on hepatocyte apoptosis induced by TGF-β1 and its potential mechanism.Methods Primary hepatocytes were extracted from healthy SD rats by in situ perfusion,cultured for 12-24h,then randomly divided into the following groups:blank control group,UA control group (UA 25μmol/L),TGF-β1 group (TGF-β1 2.5ng/ml),UA intervention group (UA 25μmol/L and TGF-β1 2.5ng/ml),DPI intervention group (DPI 0.5μmol/L and TGF-β1 2.5ng/ml).Each group was treated with drugs for corresponding time and their proliferation and apoptosis were detected by flow cytometry,the expression of CD95 (Fas) mRNA was analyzed by RT-qPCR,the expression of protein CD95 and membrane translocation of NADPH oxidase (NOX) subunit p47Phox were analyzed by Western blotting,and the reactive oxygen species (ROS) generation in primary hepatocytes was analyzed with reactive oxygen detection kit.Results UA intervention at 30min before TGF-β1 stimulating hepatocytes markedly reduced hepatocyte apoptosis (63.97 ± 3.19 vs 80.53 ± 1.56,P＜0.01) and promoted hepatocyte proliferation (18.67 ± 1.60 vs 10.83 ± 2.03,P＜0.01).UA intervention notably down-regulated the expressions of CD95 mRNA and protein (1.28 ± 0.15 vs 2.40 ± 0.25,P＜0.01;1.05 ± 0.15 vs 1.37 ± 0.18,P＜0.05),restrained membrane translocation of p47phox (1.13 ± 0.12 vs 1.76 ± 0.22,P＜0.01),and decreased ROS level in primary hepatocytes induced by TGF-β1 (2.12 ± 0.45 vs 3.23 ± 0.53,P＜0.01).Conclusion The mechanism of UA inhibiting hepatocyte apoptosis induced by TGF-β1 is likely to be that UA intervention reduced hepatocyte apoptosis by inhibiting NOX activation and decrease generation of ROS so as to down-regulate expression of CD95 in hepatocytes.

ObjectiveTo investigate the predictive factors for third-generation cephalosporin-resistant spontaneous bacterial peritonitis (SBP). MethodsA retrospective analysis was performed for the clinical data of 206 patients with liver cirrhosis who were hospitalized in the Ninth Hospital of Nanchang from January 2010 to December 2018, and all patients had SBP with positive bacteria based on ascites culture. According to drug susceptibility results, the patients were divided into third-generation cephalosporin-resistant SBP group (101 patients with third-generation cephalosporin-resistant pathogenic bacteria in ascites) and control group (105 patients with pathogenic bacteria sensitive to third-generation cephalosporin). Electronic medical records were reviewed to collect related information. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of data with skewed distribution between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. A dichotomous logistic regression analysis was used for multivariate analysis, and the Forward: LR method was used for the screening of independent variables. ResultsThere was a significant difference in the composition of pathogenic bacteria between the two groups (P＜0.001). The univariate analysis showed that a history of broad-spectrum antibiotic exposure in the past three months (χ2=12.351, P＜0001), non-first-time onset of SBP (χ2=14.427, P＜0.001), blood creatinine (χ2=-2.537, P=0.011), and blood bicarbonate (χ2=-4.592, P＜0.001) were candidate predictive factors with statistical significance between the two groups, and further multivariate analysis showed that a history of broad-spectrum antibiotic exposure in the past three months (odds ratio ［OR］=2.376, 95% confidence interval ［CI］: 1.009-5.598, P=0.048), non-first-time onset of SBP (OR=2.841, 95%CI: 1.133-7.122, P=0.026), and blood bicarbonate (OR=0.892, 95%CI: 0.818-0.973, P=0.010) had an independent predictive value for third-generation cephalosporin-resistant SBP. ConclusionA history of broad-spectrum antibiotic exposure in the past three months, non-first-time onset of SBP, and a low level of blood bicarbonate are independent predictive factors for third-generation cephalosporin-resistant SBP, and third-generation cephalosporins should be used with caution in SBP patients with these features.

Objective To explore the effect of low replacement plasma exchange(LPE)combined with double plasma molecular adsorption(DPMAS)in the treatment of patients with chronic acute liver failure(ACLF)and its influence on liver function,inflammatory cytokines and short-term prognosis.Methods One hundred patients with ACLF were randomly divided into the observation group and the control group by envelope method,with 50 cases in each group.On basis of routine symptomatic treatments(liver protection,removing jaundice,reducing enzymes,anti-viruses,bleeding prevention),the control group and the observation group were treated with plasma exchange(PE)and LPE plus DPMAS,respectively.The liver function,coagulation function,the levels of inflammatory cytokines,incidence of adverse reactions,and 90-day survival rate were compared between the two groups after treatment.Results After treatment,the liver function and coagulation function in the observation group were significantly improved(P＜0.05)and the levels of inflammatory cytokines were significantly lowered than those in the control group(P＜0.05).There was no statistically significant difference in the 90-day survival rate and the total incidence of adverse reactions between the groups(P＞0.05).Conclusion LPE combined with DPMAS can effectively improve liver function and coagulation function,and reduce levels of inflammatory cyto-kines in ACLF patients,with high safety.

Objective To investigate the prognosis and adverse reactions of patients with acute-on-chronic liver failure (ACLF) receiving artificial liver support therapy stratified by international normalized ratio (INR). Methods A total of 515 ACLF patients who received artificial liver support therapy in Department of Severe liver Disease, The Ninth Hospital of Nanchang, from January 2010 to May 2020 were enrolled, and according to the level of INR, they were divided into group A with 20 patients (INR < 1.5), group B with 115 patients (1.5≤INR < 1.9), group C with 179 patients (1.9≤INR < 2.6), group D with 61 patients (2.6≤INR < 3.2), group E with 75 patients (3.2≤INR < 4.2), and group F with 65 patients (INR≥4.2). All patients received multimodality medical treatment combined with artificial liver support therapy. The one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups。The chi-square test was used for comparison of categorical data between groups. Bonferroni correction was used for further comparison between two groups. and the receiver operating characteristic (ROC) curve was used to evaluate the value of INR and MELD scoring system in predicting the prognosis of ACLF patients. Results As for 90-day mortality rate, there was a significant difference between the six groups stratified by INR ( χ 2 =124.84, P < 0.001); there was no significant difference between groups A(25%), B(25.2%), and C(39.7%) ( P > 0.05), and there was a significant difference between groups D/E/F(65.6%, 82.7%, and 92.3%, respectively) and groups A/B/C (all P < 0.05); there was no significant difference between groups D and E and between groups E and F ( P > 0.05), and there was a significant difference between groups D and F ( P < 0.05). There was no significant difference in the incidence rate of intraoperative adverse reactions between the six groups ( χ 2 =8.956, P =0.111). INR had an area under the ROC curve of 0.786 (95% confidence interval: 0.746-0.825, P < 0.001) in predicting the prognosis of patients with ACLF receiving artificial liver support therapy, with a sensitivity of 66.7% and a specificity of 79.8%. Conclusion INR has a good value in predicting the prognosis of ACLF patients receiving artificial liver support therapy, and the artificial liver has good safety.

ObjectiveTo investigate the clinical application value of a predictive model for the efficacy of third-generation cephalosporin in the treatment of community-acquired spontaneous bacterial peritonitis （CASBP）. MethodsThis prospective study was conducted among 50 patients with liver cirrhosis and CASBP who were admitted to The Ninth Hospital of Nanchang from January 2021 to June 2022， and the patients were randomly divided into optimized treatment group and traditional treatment group， with 25 patients in each group. The patients in the optimized treatment group received ceftazidime or imipenem for initial treatment based on the above predictive model， and those in the traditional treatment group received ceftazidime for initial treatment， with the subsequent use of antibiotics adjusted based on the efficacy of initial treatment. The two groups were compared in terms of the response rate of initial treatment， cure rate on day 5， and 30-day mortality rate. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsAll patients completed the study. The optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.0% vs 60.0%， χ²=5.094， P=0.024）， while there was no significant difference in the cure rate on day 5 between the two groups （80.0% vs 56.6%， χ²=3.309， P=0.069）. As for the patients who received ceftazidime for initial treatment， the optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.9% vs 60.0%， χ²=4.341， P=0.037）， while there was no significant difference in the cure rate on day 5 between the two groups （83.3% vs 56.0%， χ²=2.425， P=0.119）. There was no significant difference in 30-day mortality rate between the two groups （8.0% vs 20.0%， χ²=0.664， P=0.415）. For all patients， there was a significant association between response of initial treatment and cure on day 5 （odds ratio ［OR］=9.643， 95% confidence interval ［CI］： 2.292‍ — ‍40.564） and between cure on day 5 and 30-day mortality （OR=0.138， 95%CI： 0.023‍ — ‍0.813）. ConclusionThis predictive model for efficacy helps clinicians to identify the patients who can benefit from third-generation cephalosporin treatment and improve the efficacy of third-generation cephalosporin in the initial empirical treatment of CASBP.

Objective To investigate the factors for predicting the efficacy of third-generation cephalosporin (3 rd GC) in the treatment of community-acquired spontaneous bacterial peritonitis (CASBP), and to establish and validate an efficacy predictive model for 3 rd GC in the treatment of CASBP. Methods A retrospective analysis was performed for the clinical data of the patients with liver cirrhosis and CASBP who received 3 rd GC monotherapy for initial treatment in The Ninth Hospital of Nanchang, and according to their treatment outcome, they were divided into non-response group and response group. The patients hospitalized from 2013 to 2018 were included in the modeling cohort (55 patients the non-response group and 110 in the response group), and those hospitalized from 2019 to 2020 were included in the validation cohort (17 patients in the non-response group and 43 in the response group). In the modeling cohort, the two groups were compared in terms of the indices including general information, underlying diseases, past history, clinical manifestation, and laboratory test results. Univariate analyses (the t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups) and a binary Logistic regression analysis were used to identify efficacy predictors, and an efficacy predictive model was established based on the logistic regression equation. The receiver operating characteristic (ROC) curve was plotted to perform internal and external validations of the model in the modeling cohort and the validation cohort, respectively. Results The study population had a mean age of 51.6±12.0 years, and male patients accounted for 80.0%; hepatitis B was the main cause of liver cirrhosis (66.7%), and 3 rd GC had an overall response rate of 68.0%. In the modeling cohort, compared with the response group, the non-response group had significantly lower proportion of patients with the first onset of SBP, polymorphonuclear (PMN) count in ascites, and leukocyte count in ascites (all P < 0.05), as well as significantly higher proportion of patients with exposure to broad-spectrum antibiotic and platelet count (both P < 0.05). The Logistic regression analysis showed that the first onset of SBP (odds ratio [ OR ]=0.158, 95% confidence interval [ CI ]: 0.064-0.392, P < 0.001), ascites PMN count ( OR =0.728, 95% CI : 0.530-0.998, P =0.046), exposure to broad-spectrum antibiotic ( OR =9.152, 95% CI : 1.513-55.351, P =0.016), and platelet count ( OR =1.012, 95% CI : 1.006-1.019, P < 0.001) were independent predictive factors for non-response to 3 rd GC. The efficacy predictive model had an area under the ROC curve (AUC) of 0.840, and based on the maximum Youden index, predictive score ≥ 0.207 was the optimal cut-off value for predicting non-response, with a corresponding Youden index of 0.536, a sensitivity of 89.1%, a specificity of 63.6%, a positive predictive value of 55.1%, and a negative predictive value of 92.1%. This model had an AUC of 0.837 in the validation cohort. Conclusion The first onset of SBP and higher ascites PMN count are the protective factors against non-response to 3 rd GC for the treatment of CASBP, and exposure to broad-spectrum antibiotic and higher platelet count are the risk factors for such non-response. The model established for predicting the efficacy of 3 rd GC in the treatment of CASBP has good predictive performance and thus holds promise for clinical application.