Liver fibrosis is a common outcome of various chronic hepatic insults, characterized by excessive extracellular matrix (ECM) deposition. The precise mechanisms, however, remain largely undefined. This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3 (Pafah1b3) in liver tissues from both carbon tetrachloride (CCl₄)-treated mice and patients with cirrhosis. Deletion of Pafah1b3 significantly attenuated CCl₄-induced fibrosis, hepatic stellate cell (HSC) activation, and activation of transforming growth factor-β (TGF-β) signaling. Mechanistically, PAFAH1B3 binds to mothers against decapentaplegic homolog 7 (SMAD7), disrupting SMAD7's interaction with TGF-β receptor 1 (TβR1), which subsequently decreases TβR1 ubiquitination and degradation. Pharmacological inhibition using 3-IN-P11, a specific Pafah1b3 inhibitor, conferred protective effects against CCl₄-induced fibrosis in mice. Furthermore, Pafah1b3 deficiency reduced hepatic inflammation. Overall, these results establish a pivotal role for Pafah1b3 in modulating TGF-β signaling and driving HSC activation.

Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Objective:To explore the suitable prostate cancer screening mode under the medical community for primary hospitals.Methods:From April 2021 to April 2022, a total of 16007 male population ≥50 years from 9 branches of the medical community of the second hospital of Yinzhou participated in this study. They were divided into four groups according to age with group 1 of 50-59 years old, group 2 of 60-69 years old, group 3 of 70-79 years old, and group 4 of 80 years old and above. Serum tPSA was added to the routine physical examination, and the screening positive patients were referred to the referral hospital for further diagnosis and treatment under the mode of medical community. We proposed multi-parametric MRI (mpMRI) for those with serum PSA ≥4 ng/ml and suspicious lesions should be scored according to PI-RADS V2. The ultrasound-guided transperineal targeted prostate biopsy was performed for those with PI-RADS ≥3 and those with PI-RADS < 3 but tPSA ≥10 ng/ml. The tPSA follow-up examinations were performed every 6 months for tPSA < 10 ng/ml and PI-RADS < 3 points and once a year for tPSA < 4 ng/ml.Results:Among the 16 007 male population ≥50 years, 2 007(12.54%) were found serum PSA ≥4 ng/ml, and 634(31.59%)were referred to the referral hospital through the medical community system. Combining tPSA and mpMRI, 271 patients underwent ultrasound-guided transperineal targeted prostate biopsy. Among them, 162 were finally diagnosed with PCa, with a biopsy positive rate of 59.78%. The detection rate of PCa in all the subjects was 1.01%. According to the pathological grade, 5(3.08%) were in ISUP group 1, 95(58.64%) in ISUP group 2-3, and 62(38.27%) in ISUP group 4-5. There were 102(62.96%), 39(24.07%) and 21(12.96%) with localized, locally advanced or metastatic PCa, respectively. The levels of tPSA in the four groups were (1.13±1.44)ng/ml, (1.77±3.45)ng/ml, (3.27±17.58)ng/ml, and (4.26±11.48)ng/ml, respectively, with statistically significant differences ( P<0.01). The positive number of biopsy in each group was 1 case(0.06%), 56 cases(0.79%), 81 cases(1.36%) and 24 cases(1.82%) respectively, with statistically significant differences ( P<0.01). The number of ISUP 4-5 grades in each group was 0, 17(30.35%), 29(35.80%), and 16(66.67%) respectively, with statistically significant differences ( P<0.01). Conclusions:Based on the medical community system, according to the tPSA screening results of the primary hospitals, it is feasible and effective to refer suspicious patients to the referral hospitals for mpMRI examination, and screen prostate cancer by ultrasound-guided transperineal prostate fusion biopsy.

Objective:To investigate the clinical efficacy and prognosis of transjugular intrahepatic portosystemic shunt (TIPS) and drug combined with endoscopic treatment in patients with liver cirrhosis and esophagogastric variceal bleeding (EGVB).Methods:From January 2012 to December 2013, at the First Affiliated Hospital of Xi′an Jiaotong University, the data of 147 patients with liver cirrhosis and EGVB undergoing TIPS or drug combined with endoscopic treatment were retrospectively collected, with 87 cases in TIPS treatment group and 60 in drug combined with endoscopic treatment group.The 5 years follow-up data were analyzed, and the overall survival rates, rebleeding-free survival rates and hepatic encephalopathy-free survival rates at 6 weeks, 1 year, 2 years and 5 years after treatment of two groups were compared. Independent sample t test, Mann-Whitney U test, chi-square test, Fisher exact test, Z test, log-rank test and trend test were used for statistical analysis. Results:There were no significant differences in age, gender, etiology, Child-Pugh classification, initial liver function, coagulation function, liver ascites, previous history of hepatic encephalopathy, blood pressure and preoperative blood transfusion history between the TIPS treatment group and combination of drugs and endoscopy treatment group (all P>0.05). Forty-one patients died within 5 years, of which 20 (48.8%) died of rebleeding and 6 (14.6%) died of hepatic encephalopathy. There were no significant differences in 6-week, 1-year and 2-year overall survival rates between the TIPS group and drug combined with endoscopic treatment group (all P>0.05), however the 5-year overall survival rate of the TIPS treatment group was higher than that of the drug combined with endoscopic treatment group (78.4% vs. 63.2%), and the difference was statistically significant ( Z=2.06, P=0.048). The 6-week, 1-year, 2-year, 5-year rebleeding-free survival rates of the TIPS group were 97.7%, 96.5%, 88.9% and 70.9%, respectively, which were all higher than those of the drug combined with endoscopic treatment group (86.7%, 53.3%, 43.3% and 27.1%), and the differences were statistically significant ( Z=2.35, 6.39, 6.26 and 4.80, all P<0.05). There were no significant differences in hepatic encephalopathy-free survival rates at 6 weeks, 1 year and 2 years after treatment between the TIPS group and drug combined with endoscopic treatment group (all P>0.05), however the 5-year hepatic encephalopathy-free survival rate of the TIPS treatment group was lower than that of the drug combined with endoscopic treatment group (67.7% vs. 86.7%), and the difference was statistically significant ( Z=2.28, P=0.030). The lower the Child-Pugh classification, the higher the cumulative 5-year survival rate ( χ2=6.75, P<0.01). There was no statistically significant difference in the 5-year overall survival rate in patients with the same Child-Pugh classification between the TIPS group and the drug combined with endoscopic treatment group (all P>0.05). Conclusions:The efficacy of TIPS is better than that of the drug combined with endoscopic treatment in treating EGVB. Even the long-term risk of hepatic encephalopathy of TIPS is higher, the short-term, middle-term and long-term rebleeding rate are decreased. Patients with Child-Pugh grade C do not need to avoid TIPS when choosing the treatment, the earlier the TIPS used, the better survival benefit will be obtained.

Objective To evaluate the efficacy and safety of emergency endoscopic needle-knife sphincterotomy in acute biliary pancreatitis caused by impacted common bile duct stones at duodenal papilla.Methods Between Jan 2007 and Jan 2017,115 cases underwent emergency endoscopic retrograde cholangiopancreatography (ERCP) and needle-knife sphincterotomy.Clinical data were recorded and analyzed.Results Procedures were successful in all cases.The mean operative time of needle-knife sphincterotomy was (22.5 ± 13.7) min.The clearence of impacted stone at duodenal papilla was 87.8％(101/115).The syptoms of pancreatitis promptly relieved after emergency ERCP.Postoperative white blood cell count,serum amylase and liver function improved significantly.The complication rate was 5.2％ (6/115),including 3 cases of hemorrhage and 3 cases of acute cholangitis,which were cured by conservative treatment.There was not procedure-related mortality.Conclusions Emergency endoscopic needle-knife precut sphincterotomy is effective and safe for acute biliary pancreatitis caused by impacted common bile duct stones at the duodenal papilla.

Objective To evaluate the application value of emergency endoscopic needle-knife sphincterotomy(NKS) on acute cholangitis of severe type (ACST) resulting from impacted common bile duct stones at duodenal papilla. Methods A retrospective study was performed on the data of 90 ACST cases with impacted common bile duct stones at the native papilla and undergoing emergency NKS between January 2011 and January 2017 in Tianjin Nankai Hospital. The completion of treatment, mean operating time, impacted stone clearance rate, changes of laboratory indexes before and after endoscopic procedure, and complications were analyzed. Results All the 90 patients underwent emergency NKS successfully, with a total success rate of 100. 0％. The mean operating time was 25. 2±11. 7 min. The impacted stone clearance rate was 95. 6％(86/90). The complication rate was 5. 6％(5/90), including 3 cases of hemorrhage and 2 cases of post-ERCP pancreatitis. There was no procedure-related mortality. The postoperative white blood cell count, serum procalcitonin, total bilirubin, direct bilirubin, and glutamic-pyruvic transaminase decreased significantly compared with pre-operation ( all P<0. 001) . Conclusion Emergency NKS is effective and safe for treatment of ACST resulting from impacted common bile duct stones at duodenal papilla with a relative high application value.

Objective To explore the effect of puncture the left or right branch of portal vein on the incidence of postoperative hepatic encephalopathy in transjugular intrahepatic portosystemic shunt (TIPS). Methods A literature search was conducted through investigating PubMed, Cochrane Library, CNKI digital library and Wanfang databases. Randomized controlled trials and cohort studies related to the effect of puncture the left or right branch of portal vein on the incidence of postoperative hepatic encephalopathy in TIPS were included in this review. According to the methods for Cochrane systematic review, the data were extracted, the quality of the literatures was evaluated, statistical analysis was conducted and the data were analyzed with RevMan 5.0. Results One randomized controlled trial and four cohort studies, including 552 patients with liver cirrhosis received TIPS, were finally included in this review. Random-effects model meta-analysis showed that puncture of the left branch of portal vein in TIPS caused lower incidence of postoperative hepatic encephalopathy than puncture of the right branch of portal vein (RR=0.51, 95%CI was 0.39 to 0.66, P<0.01). Conclusion Puncture of the left branch of portal vein in TIPS can significantly reduce the incidence of postoperative hepatic encephalopathy in comparison with puncture of the right branch of portal vein.

Objective To explore the clinical significance of tumor pathological length in evaluation of prognosis of esophageal squamous cell carcinoma.Methods 421 patients with esophageal squamous cell carcinoma were selected as study subjects.Each patient's data of gender,age,pathological examination(tumor pathological length),survival time,cancer stage,operation mode were collected.The patients were divided into two groups:≤4 cm group(189 cases) and >4 cm group(232 cases), and the constituent ratios of gender,age,or operation mode and the survival rate between the two groups were analyzed.Results There were no significant differences in gender composition,age structure and operation mode between the two groups(x2=2.03,2.41,0.06,all P>0.05);There was positive correlation between tumor pathological length and TNM stage(CMH=68.07,P<0.01).The 25%,50% and 75% quantiles of survival period in the group whose tumor length was less than or equal to 4 cm were 28,40 and 58 months,respectively,which in the group whose tumor length was more than 4 cm were 19,31 and 61 months,and there was significantly difference between the two groups(x2=44.88,P<0.01), the group whose tumor length was less than or equal to 4 cm had higher survival rate than the group whose tumor length was more than 4 cm.In the further stratification analysis by TNM stage,the group whose tumor length was less than or equal to 4 cm had higher survival rate than the group whose tumor length was more than 4 cm in theⅠstage patients(x2=5.61,P<0.05);the group whose tumor length was less than or equal to 4 cm had higher survival rate than the group whose tumor length was more than 4 cm in theⅡstage patients(x2=4.62,P<0.05);the group whose tumor length was less than or equal to 4 cm had higher survival rate than the group whose tumor length was more than 4 cm in the Ⅲ stage patients(x2=4.88,P<0.05).Conclusion Tumor pathological length is an effective prognostic factor for esophageal squamous cell carcinoma,and the critical value can be determined as 4 cm.

Objective To analyze the genomic evolution characteristics of pathogenicity islands (PAIs)in Deng strain of enteropathogenic Escherichia coli (E.coli,EPEC Deng).Methods EPEC Deng was isolated from infant stool specimen,serotypes were identified and antimicrobial susceptibility testing was performed;whole-genome se-quencing was performed by Illumina 2000 system,the locations of prophages(PPs)in the chromosome were detected using PHAST software,collinearity analysis was performed by MUMmer software,phylogenetic trees of homolo-gous gene were constructed in order to understand the evolutional rule of homology gene.PAIs prediction was per-formed using PAI finder software,the homologous evolutionary rule of PAIs core region(LEE)and core genes were clarified,genetic polymorphism was analyzed.Results The serotype of EPEC Deng strain was O119:H6,the strain was resistant to ciprofloxacin,levofloxacin,and ampicillin,but sensitive to other antimicrobial agents.The complete circular chromosome contained 5 025 482 bp with a GC content of 50.52 %,and the plasmid contained 207 564 bp with a GC content of 49.50%.A total of 17 PPs in the chromosomal genome were discovered,phyloge-netic trees analysis suggested that EPEC Deng strain was highly homologous with O26:H11 and O111 :H strains;PAIs and core genes were highly homologous with RDEC-1 and O26:H413/89-1 strains;genetic diversity analysis showed that the intimin (eae)and its receptor tir had high polymorphism,with the pi (π)value>0.10,the genes in type III secretion system was relatively stable.Conclusion The study clarified the genomic evolution characteris-tics of EPEC Deng genome and it’s PAIs,and is helpful for understanding genetic characteristics of native EPEC.

OBJECTIVE:To optimize the formulation of Dimemorfan phosphate tablets. METHODS:Using 60 min dissolution rate of dimemorfan phosphate as index,L9(34) orthogonal test was used to optimize the amount of starch,microcrystalline cellu-lose,croscarmellose sodium and concentration of HPMC E5 solution. The friability,hardness,60 min dissolution rate and main component were detected. The similarity of dissolution curves of Dimemorfan phosphate tablets was compared with that of imported tablets in 0.1 mol/L hydrochloric acid,pH 6.8 phosphate buffer,water and pH 4.0 acetate buffer. RESULTS:The optimized formu-lation of Dimemorfan phosphate tablet(1 000 tablets)was composed of dimemorfan phosphate 10 g,starch 60 g,microcrystalline cellulose 40 g,10% HPMC E5 solution and croscarmellose sodium 25 g. The friability,hardness,60 min dissolution rate and main component of 3 batches of Dimemorfan phosphate tablets prepared by optimized prescription were 0.42%-0.58%,9.8-10.5 kg,94.89%-96.21% and 99.21%-99.52%,respectively. In 4 dissolution mediums,similar factors f2 of dissolution curves between prepared tablets and imported tablets were above 50. CONCLUSIONS:Dimemorfan phosphate tablets were prepared successfully. The optimized formulation is rational. The dissolution behavior of prepared tablets is similar to that of imported tablets in vitro.