Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decompensation in patients with chronic liver disease.Liver transplantation(LT)is the most effective treatment.We aimed to...Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decompensation in patients with chronic liver disease.Liver transplantation(LT)is the most effective treatment.We aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ACLF.Methods:This was an observational cohort study conducted between January 2018 and December 2020.Clinical characteristics,cirrhosis-related complications at LT and patient survival post-LT were collected.All liver recipients with ACLF were followed for 1 year post-LT.Results:A total of 212 LT recipients with ACLF were enrolled,including 75(35.4%)patients with ACLF-1,64(30.2%)with ACLF-2,and 73(34.4%)with ACLF-3.The median waiting time for LT was 11(4-24)days.The most prevalent cirrhosis-related complication was ascites(78.8%),followed by hepatic encephalopathy(57.1%),bacterial infections(48.1%),hepatorenal syndrome(22.2%)and gastrointestinal bleeding(11.3%).Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1 year after LT than those without complications(all P<0.05).A simplified model was developed by assigning one point to each complication:transplantation for ACLF with cirrhosis-related complication(TACC)model.Risk stratification of TACC model identified 3 strata(≥4,=3,and≤2)with high,median and low risk of death after LT(P<0.001).Moreover,the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic models(chronic liver failure-consortium ACLF score,Chinese Group on the Study of Severe Hepatitis B-ACLF score,model for end-stage liver disease score and Child-Turcotte-Pugh score).Conclusions:The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with ACLF.The TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival,which might help to determine transplant timing for ACLF.展开更多
AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five gr...AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five groups:(1)Tolerance group(BN-BN LT,n=8);(2)rejection group(Lewis-BN LT,n=8);(3)high dosage FK506(FK506-H)group(Lewis-BN LT,n=8);(4)middle dosage FK506(FK506-M)group(Lewis-BN LT,n=8);and(5)low dosage FK506(FK506-L)group(LewisBN LT,n=8).FK506 was administered to recipients at a dose of 1.0 mg/kg,0.5 mg/kg,and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,FK506-M,and FK506-L groups,respectively.On the 30^(th) day after LT,all rats were sampled and euthanized.Blood samples were harvested for liver function and plasma endotoxin testing.Hepatic graft and ileocecal tissues were collected for histopathology observation.Ileocecal contents were used for DNA extraction,Real-time quantitative polymerase chain reaction(RT-PCR)and digital processing of denaturing gradient gel electrophoresis(DGGE)profiles and analysis.RESULTS Compared to the FK506-H and FK506-L groups,FK506-M was optimal for maintaining immunosuppression and inducing normal graft function;the FK506-M maintained gut barrier integrity and low plasma endotoxin levels;furthermore,DGGE results showed that FK506-M induced stable gut microbiota.Diversity analysis indicated that FK506-M increased species richness and rare species abundance,and cluster analysis confirmed the stable gut microbiota induced by FK506-M.Phylogenetic tree analysis identified crucial bacteria associated with FK506-M;seven of the nine bacteria that were decreased corresponded to Bacteroidetes,while increased bacteria were of the Bifidobacterium species.FK506-M increased Faecalibacterium prausnitzii and Bifidobacterium spp.and decreased Bacteroides-Prevotella and Enterobacteriaceae,as assessed by RT-PCR,which confirmed the crucial bacterial alterations identified through DGGE.CONCLUSION Compared to the low or high dosage of FK506,an optimal dosage of FK506 induced immunosuppression,normal graft function and stable gut microbiota following LT in rats.The stable gut microbiota presented increased probiotics and decreased potential pathogenic endotoxin-producing bacteria.These findings provide a novel strategy based on gut microbiota for immunosuppressive dosage assessment for recipients following LT.展开更多
Lead-based organic-inorganic hybrids occupy a niche in the field of optoelectronics due to exceptional semiconducting properties and potential ferroelasticity.Nevertheless,the possible toxicity of lead restricts their...Lead-based organic-inorganic hybrids occupy a niche in the field of optoelectronics due to exceptional semiconducting properties and potential ferroelasticity.Nevertheless,the possible toxicity of lead restricts their widespread application to a certain extent.Herein,two new lead-free ferroelastic semiconductors are reported:[DMMClEA]_(3)Bi_(2)Br_(9)(compound 1)and[DMMClEA]_(3)Sb_(2)Br_(9)(compound 2)(DMMClEA=N-(chloromethyl)-N,N-dimethylethylammonium),in which the inorganic framework neatly arranges with[Bi_(2)Br_(9)]^(3−)/[Sb_(2)Br_(9)]^(3−)polyhedrons shared by face,forming an A_(3)B_(2)X_(9)-type structure.Both compounds 1 and 2 possess two-step phase transitions,including a3mF2/m-type ferroelastic phase transition,based on the Aizu rule.In addition,dual dielectric switches endow the application toward sensor devices.This finding enriches A_(3)B_(2)X_(9)-type zero-dimensional hybrid ferroelastics and provides an approach to designing high-performance,lead-free perovskite semiconductors with dielectric functionality.展开更多
Background:Several studies have assessed the role of gut microbiota in various cirrhosis etiologies,however,none has done so in the context of Schistosoma joponicum infection in humans.We,therefore,sought to determine...Background:Several studies have assessed the role of gut microbiota in various cirrhosis etiologies,however,none has done so in the context of Schistosoma joponicum infection in humans.We,therefore,sought to determine whether gut microbiota is associated with S.japonicum infection-induced liver cirrhosis.Methods:From December 2017 to November 2019,24 patients with S.joponicum infection-induced liver cirrhosis,as well as 25 age-and sex-matched controls from the Zhejiang Province,China,were enrolled.Fecal samples were collected and used for 16S rRNA gene sequencing(particularly,the hypervariable V4 region)using the lllumina MiSeq system.Wilcoxon Rank-Sum and PERMANOVA tests were used for analysis.展开更多
基金supported by grants from the National Key R&D Program of China(2021YFC2301800)Zhejiang Basic Public Welfare Research Program(LGF20H030008)the National Natural Sci-ence Foundation of China(81874038)。
文摘Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decompensation in patients with chronic liver disease.Liver transplantation(LT)is the most effective treatment.We aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ACLF.Methods:This was an observational cohort study conducted between January 2018 and December 2020.Clinical characteristics,cirrhosis-related complications at LT and patient survival post-LT were collected.All liver recipients with ACLF were followed for 1 year post-LT.Results:A total of 212 LT recipients with ACLF were enrolled,including 75(35.4%)patients with ACLF-1,64(30.2%)with ACLF-2,and 73(34.4%)with ACLF-3.The median waiting time for LT was 11(4-24)days.The most prevalent cirrhosis-related complication was ascites(78.8%),followed by hepatic encephalopathy(57.1%),bacterial infections(48.1%),hepatorenal syndrome(22.2%)and gastrointestinal bleeding(11.3%).Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1 year after LT than those without complications(all P<0.05).A simplified model was developed by assigning one point to each complication:transplantation for ACLF with cirrhosis-related complication(TACC)model.Risk stratification of TACC model identified 3 strata(≥4,=3,and≤2)with high,median and low risk of death after LT(P<0.001).Moreover,the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic models(chronic liver failure-consortium ACLF score,Chinese Group on the Study of Severe Hepatitis B-ACLF score,model for end-stage liver disease score and Child-Turcotte-Pugh score).Conclusions:The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with ACLF.The TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival,which might help to determine transplant timing for ACLF.
基金Supported by the National Natural Science Foundation of China,No.81672422,No.81600506,and No.81702757Open Project in State Key Laboratory for Diagnosis and Treatment of Infectious Disease,No.2015KF03+4 种基金National S&T Major Project of China,No.2018ZX10301201Natural Science Foundation of Zhejiang Province,No.LY15H160033China Postdoctoral Science Foundation,No.2017464Zhejiang Province Health Department Program,No.2014KYB081,and No.2017KY322Academician Jieshou Li Mucosal Barrier Fund,No.201208
文摘AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five groups:(1)Tolerance group(BN-BN LT,n=8);(2)rejection group(Lewis-BN LT,n=8);(3)high dosage FK506(FK506-H)group(Lewis-BN LT,n=8);(4)middle dosage FK506(FK506-M)group(Lewis-BN LT,n=8);and(5)low dosage FK506(FK506-L)group(LewisBN LT,n=8).FK506 was administered to recipients at a dose of 1.0 mg/kg,0.5 mg/kg,and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,FK506-M,and FK506-L groups,respectively.On the 30^(th) day after LT,all rats were sampled and euthanized.Blood samples were harvested for liver function and plasma endotoxin testing.Hepatic graft and ileocecal tissues were collected for histopathology observation.Ileocecal contents were used for DNA extraction,Real-time quantitative polymerase chain reaction(RT-PCR)and digital processing of denaturing gradient gel electrophoresis(DGGE)profiles and analysis.RESULTS Compared to the FK506-H and FK506-L groups,FK506-M was optimal for maintaining immunosuppression and inducing normal graft function;the FK506-M maintained gut barrier integrity and low plasma endotoxin levels;furthermore,DGGE results showed that FK506-M induced stable gut microbiota.Diversity analysis indicated that FK506-M increased species richness and rare species abundance,and cluster analysis confirmed the stable gut microbiota induced by FK506-M.Phylogenetic tree analysis identified crucial bacteria associated with FK506-M;seven of the nine bacteria that were decreased corresponded to Bacteroidetes,while increased bacteria were of the Bifidobacterium species.FK506-M increased Faecalibacterium prausnitzii and Bifidobacterium spp.and decreased Bacteroides-Prevotella and Enterobacteriaceae,as assessed by RT-PCR,which confirmed the crucial bacterial alterations identified through DGGE.CONCLUSION Compared to the low or high dosage of FK506,an optimal dosage of FK506 induced immunosuppression,normal graft function and stable gut microbiota following LT in rats.The stable gut microbiota presented increased probiotics and decreased potential pathogenic endotoxin-producing bacteria.These findings provide a novel strategy based on gut microbiota for immunosuppressive dosage assessment for recipients following LT.
基金financially supported by the National Natural Science Foundation of China(grant no.21991141).
文摘Lead-based organic-inorganic hybrids occupy a niche in the field of optoelectronics due to exceptional semiconducting properties and potential ferroelasticity.Nevertheless,the possible toxicity of lead restricts their widespread application to a certain extent.Herein,two new lead-free ferroelastic semiconductors are reported:[DMMClEA]_(3)Bi_(2)Br_(9)(compound 1)and[DMMClEA]_(3)Sb_(2)Br_(9)(compound 2)(DMMClEA=N-(chloromethyl)-N,N-dimethylethylammonium),in which the inorganic framework neatly arranges with[Bi_(2)Br_(9)]^(3−)/[Sb_(2)Br_(9)]^(3−)polyhedrons shared by face,forming an A_(3)B_(2)X_(9)-type structure.Both compounds 1 and 2 possess two-step phase transitions,including a3mF2/m-type ferroelastic phase transition,based on the Aizu rule.In addition,dual dielectric switches endow the application toward sensor devices.This finding enriches A_(3)B_(2)X_(9)-type zero-dimensional hybrid ferroelastics and provides an approach to designing high-performance,lead-free perovskite semiconductors with dielectric functionality.
文摘Background:Several studies have assessed the role of gut microbiota in various cirrhosis etiologies,however,none has done so in the context of Schistosoma joponicum infection in humans.We,therefore,sought to determine whether gut microbiota is associated with S.japonicum infection-induced liver cirrhosis.Methods:From December 2017 to November 2019,24 patients with S.joponicum infection-induced liver cirrhosis,as well as 25 age-and sex-matched controls from the Zhejiang Province,China,were enrolled.Fecal samples were collected and used for 16S rRNA gene sequencing(particularly,the hypervariable V4 region)using the lllumina MiSeq system.Wilcoxon Rank-Sum and PERMANOVA tests were used for analysis.
