BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM To study...BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE.METHODS We searched the PubMed,Web of Science,EMBASE,and Cochrane databases using two keywords,HE,and gut microbiome.According to the inclusion and exclusion criteria,suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE.The data were analyzed using RevMan and STATA.RESULTS Seventeen studies were included:(1)A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE[-0.20,95%confidence interval(CI):-0.28 to-0.13,I2=20%];(2)The relative abundances of Lachnospiraceae(-2.73,95%CI:-4.58 to-0.87,I2=38%)and Ruminococcaceae(-2.93,95%CI:-4.29 to-1.56,I2=0%)in liver cirrhosis patients with HE was significantly lower than those in patients without HE;(3)In patients with HE,Enterococcus,Proteobacteria,Enterococcaceae,and Enterobacteriaceae proportions increased,but Ruminococcaceae,Lachnospiraceae,Prevotellaceae,and Bacteroidetes proportions decreased;(4)Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected;and(5)Differential gut microbiomes may serve as diagnostic and prognostic tools.CONCLUSION The gut microbiomes of patients with liver cirrhosis with and without HE differ.Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.展开更多
Objective:Non-lactating mastitis is a group of benign,non-specific inflammatory diseases of unknown etiology that occur during the non-lactating period in women.Treatment is mainly based on drugs and surgery,but these...Objective:Non-lactating mastitis is a group of benign,non-specific inflammatory diseases of unknown etiology that occur during the non-lactating period in women.Treatment is mainly based on drugs and surgery,but these two treatments have certain limitations and cannot meet the individual needs of patients.In recent years,thermal ablation technology has made significant progress in treating and researching breast diseases,especially in the exploratory thermal ablation treatment of non-lactating mastitis,which has achieved certain efficacy,but it is in the initial stage of development.To standardize the development and clinical practice,we have formu-lated the consensus.Methods:Seventy-three multidisciplinary experts from 48 tertiary-level hospitals carried out this work.The consensus formulation method(Delphi technique)was used to discuss and vote on the latest research advances,and formulated in light of the actual clinical situation in China.Results:Multidisciplinary experts discussed the indications and contraindications of non-lactating mastitis thermal ablation therapy,standardization of intraoperative operation,management of postoperative complica-tions,evaluation of therapeutic efficacy,and follow-up,and finally formed this consensus.Conclusions:Thermal ablation provides a new minimally invasive treatment option for non-lactating mastitis,but it is still in the process of clinical exploration,and prospective high-quality clinical studies with large samples are needed in the future.This consensus was developed to provide a reference for clinicians who are currently practicing this technique,but due to the limited number of cases and units,it will need to be revised and improved in future clinical practice.展开更多
Background and Aims:Continuous release and transmission of hepatitis B virus(HBV)is one of the main factors leading to chronic hepatitis B(CHB)infection.However,the mechanism of HBV-host interaction for optimal viral ...Background and Aims:Continuous release and transmission of hepatitis B virus(HBV)is one of the main factors leading to chronic hepatitis B(CHB)infection.However,the mechanism of HBV-host interaction for optimal viral transport is unclear.Hence,we aimed to explore how HBV manipulates microtubule-associated protein 1S(MAP1S)and microtubule(MT)to facilitate its transport and release.Methods:The expression of MAP1S or acetylated MT was investigated by immunofluorescence,RT-PCR,immunoblotting,and plasmid transfection.MAP1S overexpression or knockdown was performed by lentiviral infection or shRNA transfection,respectively.HBV DNA was quantified using q-PCR.Results:Significantly higher level of MAP1S in HepG2215 cells compared with HepG2 cells was detected using RT-PCR(p<0.01)and immunoblotting(p<0.001).Notably,stronger MAP1S expression was observed in the liver tissues of patients with CHB than in healthy controls.MAP1S overexpression or knockdown demonstrated that MAP1S promoted MT acetylation and reduced the ratio of HBV DNA copies inside to outside cells.Further,transfection with the hepatitis B virus X protein(HBx)-expressing plasmids induced significantly higher level of MAP1S than that in controls(p<0.0001),whereas HBVX−mutant-encoding HBV proteins(surface antigen,core protein,and viral DNA polymerase)hardly affected its expression.Conclusions:These results demonstrate that HBx induces the forma tion of stable MTs to promote the release of HBV particles through upregulating MAP1S.Thus,our studies delineate a unique molecular pathway through which HBV manipulates the cytoskeleton to facilitate its own transportation,and indicate the possibility of targeting MAP1S pathway for treatment of patients with CHB.展开更多
There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessar...There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.展开更多
文摘BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE.METHODS We searched the PubMed,Web of Science,EMBASE,and Cochrane databases using two keywords,HE,and gut microbiome.According to the inclusion and exclusion criteria,suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE.The data were analyzed using RevMan and STATA.RESULTS Seventeen studies were included:(1)A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE[-0.20,95%confidence interval(CI):-0.28 to-0.13,I2=20%];(2)The relative abundances of Lachnospiraceae(-2.73,95%CI:-4.58 to-0.87,I2=38%)and Ruminococcaceae(-2.93,95%CI:-4.29 to-1.56,I2=0%)in liver cirrhosis patients with HE was significantly lower than those in patients without HE;(3)In patients with HE,Enterococcus,Proteobacteria,Enterococcaceae,and Enterobacteriaceae proportions increased,but Ruminococcaceae,Lachnospiraceae,Prevotellaceae,and Bacteroidetes proportions decreased;(4)Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected;and(5)Differential gut microbiomes may serve as diagnostic and prognostic tools.CONCLUSION The gut microbiomes of patients with liver cirrhosis with and without HE differ.Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.
基金supported by the Scientific Research Program Project of Hebei Provincial Administration of Traditional Chinese Medicine(No.2025267)the Science and Technology Development Fund of Macao(0105/2022/A).
文摘Objective:Non-lactating mastitis is a group of benign,non-specific inflammatory diseases of unknown etiology that occur during the non-lactating period in women.Treatment is mainly based on drugs and surgery,but these two treatments have certain limitations and cannot meet the individual needs of patients.In recent years,thermal ablation technology has made significant progress in treating and researching breast diseases,especially in the exploratory thermal ablation treatment of non-lactating mastitis,which has achieved certain efficacy,but it is in the initial stage of development.To standardize the development and clinical practice,we have formu-lated the consensus.Methods:Seventy-three multidisciplinary experts from 48 tertiary-level hospitals carried out this work.The consensus formulation method(Delphi technique)was used to discuss and vote on the latest research advances,and formulated in light of the actual clinical situation in China.Results:Multidisciplinary experts discussed the indications and contraindications of non-lactating mastitis thermal ablation therapy,standardization of intraoperative operation,management of postoperative complica-tions,evaluation of therapeutic efficacy,and follow-up,and finally formed this consensus.Conclusions:Thermal ablation provides a new minimally invasive treatment option for non-lactating mastitis,but it is still in the process of clinical exploration,and prospective high-quality clinical studies with large samples are needed in the future.This consensus was developed to provide a reference for clinicians who are currently practicing this technique,but due to the limited number of cases and units,it will need to be revised and improved in future clinical practice.
基金supported by the Research Fund of Beijing Institute of Hepatology(Y-2021-6)WBE Liver Fibrosis Foundation(WBE2021052)+1 种基金the Capital Special Fund for Health Development(2020-1-2182)the National Science and Technology Key Project of China(2017ZX10201201).
文摘Background and Aims:Continuous release and transmission of hepatitis B virus(HBV)is one of the main factors leading to chronic hepatitis B(CHB)infection.However,the mechanism of HBV-host interaction for optimal viral transport is unclear.Hence,we aimed to explore how HBV manipulates microtubule-associated protein 1S(MAP1S)and microtubule(MT)to facilitate its transport and release.Methods:The expression of MAP1S or acetylated MT was investigated by immunofluorescence,RT-PCR,immunoblotting,and plasmid transfection.MAP1S overexpression or knockdown was performed by lentiviral infection or shRNA transfection,respectively.HBV DNA was quantified using q-PCR.Results:Significantly higher level of MAP1S in HepG2215 cells compared with HepG2 cells was detected using RT-PCR(p<0.01)and immunoblotting(p<0.001).Notably,stronger MAP1S expression was observed in the liver tissues of patients with CHB than in healthy controls.MAP1S overexpression or knockdown demonstrated that MAP1S promoted MT acetylation and reduced the ratio of HBV DNA copies inside to outside cells.Further,transfection with the hepatitis B virus X protein(HBx)-expressing plasmids induced significantly higher level of MAP1S than that in controls(p<0.0001),whereas HBVX−mutant-encoding HBV proteins(surface antigen,core protein,and viral DNA polymerase)hardly affected its expression.Conclusions:These results demonstrate that HBx induces the forma tion of stable MTs to promote the release of HBV particles through upregulating MAP1S.Thus,our studies delineate a unique molecular pathway through which HBV manipulates the cytoskeleton to facilitate its own transportation,and indicate the possibility of targeting MAP1S pathway for treatment of patients with CHB.
基金The study was supported by National Key Research and Development Program(2018YFA0704100,2018YFA0704104)National Natural Science Foundation of China(81827805,82130060)Jiangsu Provincial Special Program of Medical Science(BE2019750).The funding sources had no role in the writing of the report,or decision to submit the paper for publication.
文摘There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.