Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular...Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.展开更多
Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA reg...Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.展开更多
BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AIM To explore the characterization of AoCLD to provide theoret...BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AIM To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD.METHODS Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure(ACLF)study cohort were included in this study.The clinical characteristics and outcomes,and the 90-d survival rate associated with each clinical type of AoCLD were analyzed,using the Kaplan-Meier method and the log-rank test.RESULTS A total of 3375 patients with AoCLD were enrolled,including 1679(49.7%)patients with liver cirrhosis acute decompensation(LC-AD),850(25.2%)patients with ACLF,577(17.1%)patients with chronic hepatitis acute exacer-bation(CHAE),and 269(8.0%)patients with liver cirrhosis active phase(LC-A).The most common cause of chronic liver disease(CLD)was HBV infection(71.4%).The most common precipitants of AoCLD was bacterial infection(22.8%).The 90-d mortality rates of each clinical subtype of AoCLD were 43.4%(232/535)for type-C ACLF,36.0%(36/100)for type-B ACLF,27.0%(58/215)for type-A ACLF,9.0%(151/1679)for LC-AD,3.0%(8/269)for LC-A,and 1.2%(7/577)for CHAE.CONCLUSION HBV infection is the main cause of CLD,and bacterial infection is the main precipitant of AoCLD.The most common clinical type of AoCLD is LC-AD.Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.展开更多
Because of the diversity of the dinical and laboratory manifestations, the diagnosis of autoimmune liver disease (AILD) remains a challenge in clinical practice. The value of metabolomics has been studied in the dia...Because of the diversity of the dinical and laboratory manifestations, the diagnosis of autoimmune liver disease (AILD) remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), differed between autoimmune hepatitis (AIH) and primary biliary cir- rhosis (PBC), to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS: Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and or- thogonal partial least squares discrimination analysis. RESULTS: The partial least squares discrimination analysis model (R2y=0.991, Q2=0.943) was established between the AIH and PBC groups and exhibited both sensitivity and speci- ficity of 100%. Five groups of biomarkers were identified, in- eluding bile acids, free fatty acids, phosphatidylcholines, lyso- lecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy con- trol group. The other biomarkers decreased in the AIH andPBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS: The biomarkers identified revealed the pathophysiological changes in AILD and helped to discrimi- nate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.展开更多
Objective In this study, we evaluated the diagnostic efficiency of six recombinant proteins for the serodiagnosis of Lyme borreliosis (LB) and screened out the appropriate antigens to support the production of a Chi...Objective In this study, we evaluated the diagnostic efficiency of six recombinant proteins for the serodiagnosis of Lyme borreliosis (LB) and screened out the appropriate antigens to support the production of a Chinese clinical ELISA (enzyme-linked immunosorbent assay) kit for LB. Methods Six recombinant antigens, Fla B.g, OspC B.a, OspC B.g, P39 B.g, P83 B.g, and VlsE B.a, were used for ELISA to detect serum antibodies in LB, syphilis, and healthy controls. The ELISA results were used to generate receiver operating characteristic (ROC) curves, and the sensitivity and specificity of each protein was evaluated. All recombinant proteins were evaluated and screened by using logistic regression models. Results Two IgG (VISE and OspC B.g) and two IgM (OspC B.g and OspC B.a) antigens were left by the logistic regression model screened. VIsE had the highest specificity for syphilis samples in the IgG test (87.7%, P〈0.05). OspC B.g had the highest diagnostic value in the IgM test (AUC=0.871). Interactive effects between OspC B.a and Fla B.g could reduce the specificity of the ELISA. Conclusion Three recombinant antigens, OspC B.g, OspC B.a, and VisE B.a, were useful for ELISAs of LB. Additionally, the interaction between OspC B.a and Fla B.g should be examined in future research.展开更多
Drug-induced liver injury(DILI)is a rare side effect of drugs caused by all kinds of prescription or over-the-counter chemi-cals,biological agents,traditional Chinese medicine(TCM),natu-ral medicine(NM),health product...Drug-induced liver injury(DILI)is a rare side effect of drugs caused by all kinds of prescription or over-the-counter chemi-cals,biological agents,traditional Chinese medicine(TCM),natu-ral medicine(NM),health products,dietary supplements and their metabolites,and even excipients,which can lead to jaundice,liver failure,or even death.Although it is rare in term of single drug,the occurrence of DILI in all liver injuries is not low due to the wide range of drugs and foods involved.Moreover,there was an increasing trend of incidence of DILI since 2010 worldwide,with Asian regions showing the highest incidence[1].展开更多
Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation...Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.展开更多
To the Editor: Fatty liver diseases, including nonalcoholic fatty liver disease and alcohol related fatty liver disease, have become a major public health concern [ 1, 2 ]. Fatty liver diseases have been shown to prog...To the Editor: Fatty liver diseases, including nonalcoholic fatty liver disease and alcohol related fatty liver disease, have become a major public health concern [ 1, 2 ]. Fatty liver diseases have been shown to progress through various stages, from steatosis or necrosis with inflammation and hepatocyte damage to the development of fibrosis and eventual cirrhosis with an increased risk of carcinoma [ 2, 3 ].展开更多
Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the b...Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron,inducing immune cells to secrete various cytokines to enhance systemic immune responses,or recruiting neutrophils to infectious sites.The liver serves as the primary organ for LCN2 secretion during microbial infections.This review encapsulates recent advances in dynamic changes,clinical values,and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.展开更多
In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic indiv...In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.展开更多
AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease(NAFLD) in a Chinese population.METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study ...AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease(NAFLD) in a Chinese population.METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study was performed to investigate the prevalence of NAFLD at baseline, and then the participants were followed for 8 years to investigate risk factors for the development of NAFLD.RESULTS: A total of 1948 participants were enrolled at baseline, of whom 691 were diagnosed with NAFLD. During the 8-year follow-up, 337 baseline NAFLD-free participants developed NAFLD. They had a greaterincrease in body mass index(BMI), serum uric acid, fasting plasma glucose, very low-density lipoprotein cholesterol and a considerable decrease in high-density lipoprotein cholesterol. 123 participants who had NAFLD at baseline lost NAFLD during the 8-year follow-up period. They had a greater decrease in BMI, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase.CONCLUSION: NAFLD is prevalent in Chinese population with a rapidly increasing tendency. It can be reversed when patients lose their weight, control their hyperlipidemia and hyperglycemia, and reduce the liver enzyme levels.展开更多
AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepati...AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.展开更多
AIM: To construct and evaluate the functionality of a choanoid-fluidized bed bioreactor (CFBB) based on microencapsulated immortalized human hepatocytes.
AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance.METHODS: A total of 1106 Helicobacter pylori(H. pylori)-positive patients were divided into three groups,ea...AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance.METHODS: A total of 1106 Helicobacter pylori(H. pylori)-positive patients were divided into three groups,each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the 13C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by χ2 tests.RESULTS: The eradication rates in groups A,B and C were 90.71%(332/366),90.46%(313/346) and 90.87%(189/208),respectively(P = 0.986). The resistance rates were 8.91% for clarithromycin,14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin-and levofloxacin-resistant patients(P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients(P = 0.034). However,levofloxacin resistance had no obvious influence on the eradication rate. Furthermore,three main antibiotics(clarithromycin,levofloxacin and amoxicillin) had lower DID(defined daily dose per 1000 inhabitants per day) in this city.CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance,a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions.展开更多
AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preem...AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preemptive antiHBV therapy for preventing HBV reactivation.METHODS The Pub Med, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAAbased therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis Bsurface antigen(HBs Ag)-positive patients receiving DAAbased therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBs Agpositive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy(RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBs Agpositive patients undergoing DAA-based therapy(RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBs Ag-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.展开更多
Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.T...Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.展开更多
Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions.Conventional systemic chemotherapy has failed in HCC,and th...Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions.Conventional systemic chemotherapy has failed in HCC,and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains unsatisfactory.Data sources:Literature search was conducted in Pub Med for relevant articles published before January 2021.The search aimed to identify recent developments in immune-based treatment approaches for HCC.Information of clinical trials was obtained from https://clinicaltrials.gov/.Results:Two immune checkpoint inhibitors(ICIs),nivolumab and pembrolizumab were approved as monotherapies,which has revolutionized HCC treatment.Besides,combination ICIs have also got accelerated FDA approval recently.Immune-based therapies have challenged targeted drugs owing to their safety,tolerability,and survival benefits.In addition to the significant success in ICIs,other immunotherapeutic strategies such as cancer vaccine,chimeric antigen receptor T-cells,natural killer cells,cytokines,and combination therapy,have also shown promising outcomes in clinical trials.Various diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ICIs.Conclusions:Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent years.However,challenges such as low response rate and acquired resistance in previously respondent patients still exist.Further research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.展开更多
BACKGROUND: Plasma exchange (PE)-centered artificial liver support system reduced the high mortality rate of hepa titis B virus (HBV)-related acute-on-chronic liver failure (ACLF). But the data were diverse in ...BACKGROUND: Plasma exchange (PE)-centered artificial liver support system reduced the high mortality rate of hepa titis B virus (HBV)-related acute-on-chronic liver failure (ACLF). But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.展开更多
Background: Cirrhotic patients are susceptible to Clostridium difficile infection(CDI), however, the high risk factors are not clear. The present study aimed to identify the risk factors in cirrhotic patients with CDI...Background: Cirrhotic patients are susceptible to Clostridium difficile infection(CDI), however, the high risk factors are not clear. The present study aimed to identify the risk factors in cirrhotic patients with CDI. Methods: A total of 526 cirrhotic patients admitted to our hospital between May 2015 and October 2015 were included in this study. Stool samples were collected upon admission for the detection of CDI and toxin. CDI was monitored during the hospital stay. In total, 34 cases showed CDI. Then we analyzed the effects of age, sex, C. difficile colonization(CDC), multiple hospitalization, extended hospital stay, elevation of total bilirubin(TBIL), creatinine(Cr), Child-Pugh grade C, hepatic encephalopathy, hepatorenal syndrome, upper gastrointestinal hemorrhage, and exposure of antibiotics and proton pump inhibitor(PPI) on the CDI in cirrhotic patients. Results: Patients in the CDI group had more frequent CDC, multiple hospitalization, and extended hospital stay compared to those in the non-C. difficile infection(NCDI) group. Patients in the CDI group had higher TBIL and Cr, and higher frequency of Child-Pugh grade C, hepatic encephalopathy, upper gastrointestinal hemorrhage compared with those in the NCDI group. Multiple logistic regression analysis indicated that age > 60 years(OR = 1.689;95% CI: 1.135–3.128), multiple hospitalization(OR = 3.346;95% CI: 1.392–8.043), length of hospital stay > 20 days(OR = 1.564;95% CI: 1.113–2.563), hypoproteinemia(OR = 4.962;95% CI: 2.053–11.996), CDC(OR = 18.410;95% CI: 6.898–49.136), hepatic encephalopathy(OR = 1.357;95% CI: 1.154–2.368), and exposure of antibiotics(OR = 1.865;95% CI: 1.213–2.863) and PPI(OR = 3.125;95% CI: 1.818–7.548) were risk factors of CDI. Conclusions: Age > 60 years, multiple hospitalization, length of hospital stay > 20 days, hypoproteinemia, CDC, hepatic encephalopathy, and exposure of antibiotics and PPI were risk factors for CDI in cirrhotic patients. These may contribute to the early diagnosis and monitoring of CDI in clinical practice.展开更多
基金supported by the National Natural Science Foundation of China,No.82101340(to FJ).
文摘Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.
基金This study was supported by grants from the High-level Preresearch Program of Zhejiang Shuren University 2019(KXJ121860)Zhejiang Provincial Natural Science Foundation of China(LQ20H190004)。
文摘Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.
基金Supported by The National Science and Technology Major Project,No.2018ZX10723203 and No.2018ZX10302206Hubei Province’s Outstanding Medical Academic Leader Program,Advantage Discipline Group(Public Health)Project in Higher Education of Hubei Province,No.2023PHXKQ1+2 种基金The Foundation of Health Commission of Hubei Province,No.WJ2021F037 and No.WJ2021M051Project of Hubei University of Medicine,No.FDFR201902 and No.YC2023047and The Hubei Provincial Technology Innovation Project,No.2023BCB129.
文摘BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AIM To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD.METHODS Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure(ACLF)study cohort were included in this study.The clinical characteristics and outcomes,and the 90-d survival rate associated with each clinical type of AoCLD were analyzed,using the Kaplan-Meier method and the log-rank test.RESULTS A total of 3375 patients with AoCLD were enrolled,including 1679(49.7%)patients with liver cirrhosis acute decompensation(LC-AD),850(25.2%)patients with ACLF,577(17.1%)patients with chronic hepatitis acute exacer-bation(CHAE),and 269(8.0%)patients with liver cirrhosis active phase(LC-A).The most common cause of chronic liver disease(CLD)was HBV infection(71.4%).The most common precipitants of AoCLD was bacterial infection(22.8%).The 90-d mortality rates of each clinical subtype of AoCLD were 43.4%(232/535)for type-C ACLF,36.0%(36/100)for type-B ACLF,27.0%(58/215)for type-A ACLF,9.0%(151/1679)for LC-AD,3.0%(8/269)for LC-A,and 1.2%(7/577)for CHAE.CONCLUSION HBV infection is the main cause of CLD,and bacterial infection is the main precipitant of AoCLD.The most common clinical type of AoCLD is LC-AD.Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.
基金supported by grants from the National Grand Program on Key Infectious Diseases(2012ZX10002-004)the National Natural Science Foundation of China(81100286)
文摘Because of the diversity of the dinical and laboratory manifestations, the diagnosis of autoimmune liver disease (AILD) remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), differed between autoimmune hepatitis (AIH) and primary biliary cir- rhosis (PBC), to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS: Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and or- thogonal partial least squares discrimination analysis. RESULTS: The partial least squares discrimination analysis model (R2y=0.991, Q2=0.943) was established between the AIH and PBC groups and exhibited both sensitivity and speci- ficity of 100%. Five groups of biomarkers were identified, in- eluding bile acids, free fatty acids, phosphatidylcholines, lyso- lecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy con- trol group. The other biomarkers decreased in the AIH andPBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS: The biomarkers identified revealed the pathophysiological changes in AILD and helped to discrimi- nate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.
基金supported by the National Science and Technology Major Project[No.2013ZX10004-001]
文摘Objective In this study, we evaluated the diagnostic efficiency of six recombinant proteins for the serodiagnosis of Lyme borreliosis (LB) and screened out the appropriate antigens to support the production of a Chinese clinical ELISA (enzyme-linked immunosorbent assay) kit for LB. Methods Six recombinant antigens, Fla B.g, OspC B.a, OspC B.g, P39 B.g, P83 B.g, and VlsE B.a, were used for ELISA to detect serum antibodies in LB, syphilis, and healthy controls. The ELISA results were used to generate receiver operating characteristic (ROC) curves, and the sensitivity and specificity of each protein was evaluated. All recombinant proteins were evaluated and screened by using logistic regression models. Results Two IgG (VISE and OspC B.g) and two IgM (OspC B.g and OspC B.a) antigens were left by the logistic regression model screened. VIsE had the highest specificity for syphilis samples in the IgG test (87.7%, P〈0.05). OspC B.g had the highest diagnostic value in the IgM test (AUC=0.871). Interactive effects between OspC B.a and Fla B.g could reduce the specificity of the ELISA. Conclusion Three recombinant antigens, OspC B.g, OspC B.a, and VisE B.a, were useful for ELISAs of LB. Additionally, the interaction between OspC B.a and Fla B.g should be examined in future research.
基金National Key R&D Pro-gram of China(2022YFC3602000)Zhejiang Provincial Natural Science Foundation of China(LZ22H030001).
文摘Drug-induced liver injury(DILI)is a rare side effect of drugs caused by all kinds of prescription or over-the-counter chemi-cals,biological agents,traditional Chinese medicine(TCM),natu-ral medicine(NM),health products,dietary supplements and their metabolites,and even excipients,which can lead to jaundice,liver failure,or even death.Although it is rare in term of single drug,the occurrence of DILI in all liver injuries is not low due to the wide range of drugs and foods involved.Moreover,there was an increasing trend of incidence of DILI since 2010 worldwide,with Asian regions showing the highest incidence[1].
基金supported by grants for National Key Research and Development Program of China(No.2020YFA0113003)Key Research and Development Project of Zhejiang Province(No.2023C03046)+1 种基金Fundamental Research Funds for the Central Universities(No.2022ZFJH003)Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2022026C,JNL-2023003C).
文摘Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.
文摘To the Editor: Fatty liver diseases, including nonalcoholic fatty liver disease and alcohol related fatty liver disease, have become a major public health concern [ 1, 2 ]. Fatty liver diseases have been shown to progress through various stages, from steatosis or necrosis with inflammation and hepatocyte damage to the development of fibrosis and eventual cirrhosis with an increased risk of carcinoma [ 2, 3 ].
文摘Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron,inducing immune cells to secrete various cytokines to enhance systemic immune responses,or recruiting neutrophils to infectious sites.The liver serves as the primary organ for LCN2 secretion during microbial infections.This review encapsulates recent advances in dynamic changes,clinical values,and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.
文摘In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.
基金Supported by the National Natural Science Foundation of China,No.81372425 and No.81460634the Key Lab Project of the Xinjiang Science and Technology Bureau,No.2014KL002
文摘AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease(NAFLD) in a Chinese population.METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study was performed to investigate the prevalence of NAFLD at baseline, and then the participants were followed for 8 years to investigate risk factors for the development of NAFLD.RESULTS: A total of 1948 participants were enrolled at baseline, of whom 691 were diagnosed with NAFLD. During the 8-year follow-up, 337 baseline NAFLD-free participants developed NAFLD. They had a greaterincrease in body mass index(BMI), serum uric acid, fasting plasma glucose, very low-density lipoprotein cholesterol and a considerable decrease in high-density lipoprotein cholesterol. 123 participants who had NAFLD at baseline lost NAFLD during the 8-year follow-up period. They had a greater decrease in BMI, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase.CONCLUSION: NAFLD is prevalent in Chinese population with a rapidly increasing tendency. It can be reversed when patients lose their weight, control their hyperlipidemia and hyperglycemia, and reduce the liver enzyme levels.
基金Supported by National Key Program for Infectious Diseases of China(to Yang YD),No.2013ZX1000200112th FiveYear Significant New Drugs Creation Plan of the Ministry of Science and Technology of China(to Yang YD),No.2011ZX09302-003-03
文摘AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.
基金Supported by The Grants from the National Scientific and Technological Major Project of China,No.2011ZX10004-901,No.2013ZX10004904the National Science and Technology Major Project,No.2012ZX10002006
文摘AIM: To construct and evaluate the functionality of a choanoid-fluidized bed bioreactor (CFBB) based on microencapsulated immortalized human hepatocytes.
基金Supported by Science and Technology Program of Zhejiang Province,China,No.2001C23140National Technology R and D Program in the 12th Five-Year Plan of China,No.2012BAI06B02+2 种基金Major Technology Project as part of"Prevention and Control of Major Infectious Diseases including AIDS and Viral Hepatitis",No.2013ZX10004216-002National Key Scientific Instrument and Equipment Development ProjectNo.2012YQ180117
文摘AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance.METHODS: A total of 1106 Helicobacter pylori(H. pylori)-positive patients were divided into three groups,each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the 13C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by χ2 tests.RESULTS: The eradication rates in groups A,B and C were 90.71%(332/366),90.46%(313/346) and 90.87%(189/208),respectively(P = 0.986). The resistance rates were 8.91% for clarithromycin,14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin-and levofloxacin-resistant patients(P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients(P = 0.034). However,levofloxacin resistance had no obvious influence on the eradication rate. Furthermore,three main antibiotics(clarithromycin,levofloxacin and amoxicillin) had lower DID(defined daily dose per 1000 inhabitants per day) in this city.CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance,a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions.
文摘AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preemptive antiHBV therapy for preventing HBV reactivation.METHODS The Pub Med, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAAbased therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis Bsurface antigen(HBs Ag)-positive patients receiving DAAbased therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBs Agpositive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy(RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBs Agpositive patients undergoing DAA-based therapy(RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBs Ag-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.
基金supported by grants from the Science&Technology Key Program of Zhejiang China(2017C03051)the National Science&Technology Major Project of China(2017ZX10203201)。
文摘Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.
基金supported by grants from the National S&T Major Project(2017ZX10203205)Key Research&Development Plan of Zhejiang Province(2019C03050)。
文摘Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions.Conventional systemic chemotherapy has failed in HCC,and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains unsatisfactory.Data sources:Literature search was conducted in Pub Med for relevant articles published before January 2021.The search aimed to identify recent developments in immune-based treatment approaches for HCC.Information of clinical trials was obtained from https://clinicaltrials.gov/.Results:Two immune checkpoint inhibitors(ICIs),nivolumab and pembrolizumab were approved as monotherapies,which has revolutionized HCC treatment.Besides,combination ICIs have also got accelerated FDA approval recently.Immune-based therapies have challenged targeted drugs owing to their safety,tolerability,and survival benefits.In addition to the significant success in ICIs,other immunotherapeutic strategies such as cancer vaccine,chimeric antigen receptor T-cells,natural killer cells,cytokines,and combination therapy,have also shown promising outcomes in clinical trials.Various diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ICIs.Conclusions:Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent years.However,challenges such as low response rate and acquired resistance in previously respondent patients still exist.Further research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.
基金supported by grants from the National Science and Technology Major Project(2012ZX10002004)Scientific Research Fund of Zhejiang Provincial Education Department(Y201328037)the opening foundation of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,First Affiliated Hospital,Zhejiang University School of Medicine(2015KF04)
文摘BACKGROUND: Plasma exchange (PE)-centered artificial liver support system reduced the high mortality rate of hepa titis B virus (HBV)-related acute-on-chronic liver failure (ACLF). But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.
基金supported by a grant from the National S&T Ma-jor Project(2012ZX10002004-001)
文摘Background: Cirrhotic patients are susceptible to Clostridium difficile infection(CDI), however, the high risk factors are not clear. The present study aimed to identify the risk factors in cirrhotic patients with CDI. Methods: A total of 526 cirrhotic patients admitted to our hospital between May 2015 and October 2015 were included in this study. Stool samples were collected upon admission for the detection of CDI and toxin. CDI was monitored during the hospital stay. In total, 34 cases showed CDI. Then we analyzed the effects of age, sex, C. difficile colonization(CDC), multiple hospitalization, extended hospital stay, elevation of total bilirubin(TBIL), creatinine(Cr), Child-Pugh grade C, hepatic encephalopathy, hepatorenal syndrome, upper gastrointestinal hemorrhage, and exposure of antibiotics and proton pump inhibitor(PPI) on the CDI in cirrhotic patients. Results: Patients in the CDI group had more frequent CDC, multiple hospitalization, and extended hospital stay compared to those in the non-C. difficile infection(NCDI) group. Patients in the CDI group had higher TBIL and Cr, and higher frequency of Child-Pugh grade C, hepatic encephalopathy, upper gastrointestinal hemorrhage compared with those in the NCDI group. Multiple logistic regression analysis indicated that age > 60 years(OR = 1.689;95% CI: 1.135–3.128), multiple hospitalization(OR = 3.346;95% CI: 1.392–8.043), length of hospital stay > 20 days(OR = 1.564;95% CI: 1.113–2.563), hypoproteinemia(OR = 4.962;95% CI: 2.053–11.996), CDC(OR = 18.410;95% CI: 6.898–49.136), hepatic encephalopathy(OR = 1.357;95% CI: 1.154–2.368), and exposure of antibiotics(OR = 1.865;95% CI: 1.213–2.863) and PPI(OR = 3.125;95% CI: 1.818–7.548) were risk factors of CDI. Conclusions: Age > 60 years, multiple hospitalization, length of hospital stay > 20 days, hypoproteinemia, CDC, hepatic encephalopathy, and exposure of antibiotics and PPI were risk factors for CDI in cirrhotic patients. These may contribute to the early diagnosis and monitoring of CDI in clinical practice.