Objective To investigate the composition ratios and trends of different etiologies after liver biopsy for patients with unexplained liver diseases.Methods A retrospective analysis was performed for the etiology of 960 patients with unexplained liver diseases who were hospitalized and underwent liver biopsy in The Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to December 2020,and the etiologies were categorized by year and age group.The chi-square test was used for comparison of categorical data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups.Results There was a tendency of increase in the overall composition ratio of unexplained liver diseases over the past decade.The leading diagnosis after liver biopsy was autoimmune liver disease(AILD)in 306 patients(31.9%),followed by nonalcoholic fatty liver disease(NAFLD)in 95 patients(9.9%)and drug-induced liver disease(DILI)in 82 patients(8.5%),and there were still 320 patients with undetermined causes(33.3%).There were significant differences in sex ratio and median age distribution between the patients with different etiologies(sex ratio:χ2=155.36,P<0.001;median age distribution:H=182.48,P<0.001).AILD had been the leading etiology in 2011-2020,and there was a tendency of reduction in the composition ratio of AILD(χ2=24.40,P<0.001).NAFLD accounted for the highest proportion of 17.6%in the adolescent stage,while AILD accounted for the highest proportion of 17.8%,47.3%,and 56.3%,respectively,in the young,middle-aged,and elderly stages.Conclusion There is a tendency of increase in the composition ratio of unexplained liver diseases in patients undergoing liver biopsy,with AILD being the main disease diagnosed after liver biopsy,followed by NAFLD and DILI,but one-third of the patients still have an unclear etiological diagnosis.

Objective To investigate the role and molecular mechanisms of bladder cancer-derived exosomal long non-coding RNA(lncRNA)CIAT1 in mediating collective invasion and to evaluate its clinical significance and potential therapeutic value.Methods High-throughput sequencing was used to identify lncRNAs that are highly expressed in exosomes from bladder cancer and lymph node metastatic tissues.CIAT1 was selected for further validation in clinical bladder cancer samples.By constructing CIAT1-overexpressing and knockdown bladder cancer cells,we demonstrated in vitro that CIAT1-contained exosomes target cancer-associated fibroblasts(CAFs)to induce collective invasion.The underlying mechanism of CIAT1 in bladder cancer collective invasion was explored through RNA pull-down,RNA immunoprecipitation(RIP),dual-luciferase reporter assays,chromatin isolation by RNA purification(ChIRP)and chromatin immunoprecipitation(ChIP).Results CIAT1 was significantly upregulated in exosomes derived from bladder cancer tissues compared to adjacent normal tissues by High-throughput sequencing(fold change>1.5,P<0.05)and clinical sample validation(P<0.01).In vitro experiments,exosomal CIAT1 was selectively internalized by cancer-associated fibroblasts(CAFs),significantly enhancing collective invasion of bladder cancer via regulating CAFs.In co-culture models,CIAT1 overexpression group showed increased total number and total length of collective invasion chains compared to the control group(P<0.01 for both).Mechanistically,CIAT1 was packaged into exosomes via binding to hnRNPA2B1,and internalized by CAFs,where it activated N-cadherin transcription by modulating H3K4me3 histone modification at the N-cadherin promoter.Consistently,the CIAT1 overexpression group exhibited elevated collective invasion chain numbers and lengths compared to the control group(P<0.01 for both).However,blocking N-cadherin reversed the pro-invasive effects of CIAT1,with no significant differences in chain numbers or lengths between the CIAT1 overexpression+N-cadherin blockade group and controls(P>0.05 for both).Further clinical correlation analysis confirmed that CIAT1-regulated N-cadherin is closely associated with collective invasion in bladder cancer patients(P<0.01).Conclusions Exosomal CIAT1 derived from bladder cancer cells targets CAFs to activate N-cadherin transcription,thereby promoting bladder cancer collective invasion.

Objective To investigate the role and molecular mechanisms of bladder cancer-derived exosomal long non-coding RNA(lncRNA)CIAT1 in mediating collective invasion and to evaluate its clinical significance and potential therapeutic value.Methods High-throughput sequencing was used to identify lncRNAs that are highly expressed in exosomes from bladder cancer and lymph node metastatic tissues.CIAT1 was selected for further validation in clinical bladder cancer samples.By constructing CIAT1-overexpressing and knockdown bladder cancer cells,we demonstrated in vitro that CIAT1-contained exosomes target cancer-associated fibroblasts(CAFs)to induce collective invasion.The underlying mechanism of CIAT1 in bladder cancer collective invasion was explored through RNA pull-down,RNA immunoprecipitation(RIP),dual-luciferase reporter assays,chromatin isolation by RNA purification(ChIRP)and chromatin immunoprecipitation(ChIP).Results CIAT1 was significantly upregulated in exosomes derived from bladder cancer tissues compared to adjacent normal tissues by High-throughput sequencing(fold change>1.5,P<0.05)and clinical sample validation(P<0.01).In vitro experiments,exosomal CIAT1 was selectively internalized by cancer-associated fibroblasts(CAFs),significantly enhancing collective invasion of bladder cancer via regulating CAFs.In co-culture models,CIAT1 overexpression group showed increased total number and total length of collective invasion chains compared to the control group(P<0.01 for both).Mechanistically,CIAT1 was packaged into exosomes via binding to hnRNPA2B1,and internalized by CAFs,where it activated N-cadherin transcription by modulating H3K4me3 histone modification at the N-cadherin promoter.Consistently,the CIAT1 overexpression group exhibited elevated collective invasion chain numbers and lengths compared to the control group(P<0.01 for both).However,blocking N-cadherin reversed the pro-invasive effects of CIAT1,with no significant differences in chain numbers or lengths between the CIAT1 overexpression+N-cadherin blockade group and controls(P>0.05 for both).Further clinical correlation analysis confirmed that CIAT1-regulated N-cadherin is closely associated with collective invasion in bladder cancer patients(P<0.01).Conclusions Exosomal CIAT1 derived from bladder cancer cells targets CAFs to activate N-cadherin transcription,thereby promoting bladder cancer collective invasion.

Objective To investigate the composition ratios and trends of different etiologies after liver biopsy for patients with unexplained liver diseases.Methods A retrospective analysis was performed for the etiology of 960 patients with unexplained liver diseases who were hospitalized and underwent liver biopsy in The Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to December 2020,and the etiologies were categorized by year and age group.The chi-square test was used for comparison of categorical data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups.Results There was a tendency of increase in the overall composition ratio of unexplained liver diseases over the past decade.The leading diagnosis after liver biopsy was autoimmune liver disease(AILD)in 306 patients(31.9%),followed by nonalcoholic fatty liver disease(NAFLD)in 95 patients(9.9%)and drug-induced liver disease(DILI)in 82 patients(8.5%),and there were still 320 patients with undetermined causes(33.3%).There were significant differences in sex ratio and median age distribution between the patients with different etiologies(sex ratio:χ2=155.36,P<0.001;median age distribution:H=182.48,P<0.001).AILD had been the leading etiology in 2011-2020,and there was a tendency of reduction in the composition ratio of AILD(χ2=24.40,P<0.001).NAFLD accounted for the highest proportion of 17.6%in the adolescent stage,while AILD accounted for the highest proportion of 17.8%,47.3%,and 56.3%,respectively,in the young,middle-aged,and elderly stages.Conclusion There is a tendency of increase in the composition ratio of unexplained liver diseases in patients undergoing liver biopsy,with AILD being the main disease diagnosed after liver biopsy,followed by NAFLD and DILI,but one-third of the patients still have an unclear etiological diagnosis.

With the increasing life expectancy and lifestyle changes of patients with chronic hepatitis B (CHB), the significance of comorbidities of chronic non-communicable diseases (NCDs) in disease progression and health prognosis of CHB patients is gaining prominence. This study aims to explore the association between CHB and NCDs comorbidities, focusing on the impact of common metabolism-related diseases, such as metabolic syndrome and diabetes, on the health outcomes of CHB patients. We also summarize studies on integrating the management of comorbidities in CHB patients and provide relevant recommendations for effective management. The findings of this study serve as a foundation for understanding the clinical characteristics and prevalence trends, reducing the disease burden of comorbidities among CHB patients, and establishing a comprehensive and coordinated management system for comorbidities.

Objective To study the effects of vagus nerve stimulation (VNS) on brain tissue tumor necrosis factor-α (TNF-o),interleukin-1β (IL-1β) and IL-10 levels in serum and brain tissues after blast brain injury in rabbits.Methods Twenty New Zealand white male rabbits were randomly divided into sham-operated group (n=6),traumatic brain injury (TBI) group (n=10),TBI+VNS group (n=8).Rabbit brain blast injury models of TBI group and TBI+VNS group were established; and the right cervical vagus nerves of the rabbits in TBI+VNS group were stimulated (10 V,5 HZ,5 ms,20 min).The TNF-α,IL-1β and IL-10 changes in the serum (6 h after injury) and brain tissues (24 h after injury) and the water content in the injured brain tissues were observed and recorded.Results The TNF-α and IL-1β levels in the serum and brain tissues,the water content in the brain tissues of the TBI group were significantly higher than those in the sham-operated group and TBI+VNS group (P＜0.05); the IL-10 level in the TBI+VNS group was significantly higher than that in the sham-operated group and TBI group (P＜0.05).Conclusion VNS can reduce the brain edema degree by increasing the IL-10 level and decreasing the TNF-α and IL-1 β levels,which plays a key role in brain protection effect after brain blast injury in rabbits.