Objective To investigate the effect of Xuesetong Dripping Pills combined with alprostadil intervention on serum brain natriuretic peptide in elderly patients with chronic congestive heart failure.Methods In 74 patients with chronic congestive heart failure, were randomly divided into observation group and control group, 37 cases in each group.Control group received conventional method.The observation group received Xuesetong Dripping Pills combined with alprostadil on the basis of conventional therapy.Compared the efficacy, the heart function level, walking test and level of serum brain natriuretic peptide between two groups after 15 days’ treatment.Results The total efficiency of observation group was 94.59%, which was higher than 75.68% in the control group, the difference was statistically significant(P<0.05).After treatment, the heart function level improvement in the observation group was better than the control group, the difference was statistically significant(P<0.05).After treatment, 6 min walking test in the observation group(316.4 ±20.7) m, was better than the control group(303.5 ±28.1) m, the difference was statistically significant(P<0.05).The level of serum brain natriuretic peptide in the observation group(608.9 ±158.1)ng/L, was lower than that of the control group(792.7 ±179.4) ng/L, the difference was statistically significant ( P <0.05 ) .Conclusion Xuesetong Dripping Pills combined with alprostadil has good curative effect in the treatment of chronic congestive heart failure,can relieve the abnormal increase of serum brain natriuretic peptide, improve blood circulation and heart function.

Objective To observe the effect of astragalus polysaccharides ( APS) on glucose homeostasis regulation and focus on glycogen synthase kinase 3 beta (GSK3 beta) activity and subcellular localization (nuclear translocation).Methods HepG2 human hepatoma cells were cultured in vitro and treated with high glucose of different concentrations (30, 40 mM) to induce hepatocyte endoplasmic reticulum stress model, then acquire optimum operating concentration.The HepG2 cells were treated with APS of different concentrations (50, 100, 200, 400 μg/mL) to select the most effective concentration.The HepG2 cells were divided into seven groups with different treatment: negative control group (C), positive control group (Tm), 30 mM high glucose-induced group (G30), 45 mM high glucose-induced group (G45), negative control+APS group (CA), positive control+APS group ( TA) and high glucose-induced+APS group ( GA).Effect of APS at different concentrations on proliferation activity of HepG2 cells were detected by MTT assay, transcription and shear levels of XBPlmRNA in HepG2 cells by quantitative real-time PCR, and phosphorylation levels of GSK3βin cytoplasm and nucleus by immunoblotting techniques.Results The optimum operating glucose concentration was 30 mM.The most effective APS concentration was 200μg/mL.The transcription and shear levels of XBPlmRNA in HepG2 cells of GA group were lower than those of G30 group ( P<0.05), respectively, but there were no significant differences between TA and Tm group.The phosphorylation levels of GSK3βin cytoplasm and nucleus of GA group were higher than those of G group(P<0.05), respectively, but there were no significant differences between TA and Tm group. Conclusion APS could improve hepatic steatosis, and its mechanism might be that APS inhibits the activity and nuclear localization of GSK3β, then alleviate endoplasmic reticulum stress.

Liver macrophages are in a dynamic equilibrium of immune tolerance and immune response after continuous antigen stimulation. The immune response of liver macrophages to external antigen is closely associated with the immune homeostasis of the liver. This article reviews the association between the programmed necrosis pathway and the apoptotic pathway and elaborates on the important role of the activity of IKK complex in the interactive regulation of the programmed necrosis and apoptotic pathways. Further studies are needed to clarify the role of programmed necrosis in the response of liver macrophages to extrahepatic antigens.

Hepatolenticular degeneration (HLD) is an autosomal recessive liver disease associated with copper metabolism disorders. Mutations in the ATP7B gene on chromosome 13 result in impaired transmembrane transport of copper ions, which in turn leads to excessive deposition of copper in the liver, brain, cornea, kidney, and bone joints (mainly in the liver and the brain). Early diagnosis and treatment can significantly reduce tissue damage and improve the prognosis of patients. American Association for the Study of Liver Diseases issued the guidelines for the diagnosis and treatment of HLD in 2008, and the European Association for the Study of the Liver released such guidelines in 2012. This article summarizes the recent research advances in China and foreign countries to give an overview of the treatment of HLD.

Objective To identify the histological features as well as factors influencing the course of HBeAg-negative chronic hepatitis B virus ( HBV)-infected patients with persistently normal alanine amino-transferase (ALT) levels (PNAL). Methods Ninety-eight HBeAg-negative chronic HBV-infected patients with PNAL who underwent percutaneous liver biopsy were recruited from October 2003 to March 2008. The ALT level, HBV markers, HBV DNA level and liver histological changes were detected. Comparison of means was done by t test and single factor analysis of variance. Nonparametric statistics was done by Marm-Whitey U test and Kruskal-Wallis test. Analysis of independent risk factor was done using Logistic model. The dianostic value of ALT level to significant liver histological changes was evaluated by receiver performance curve. Results Twenty-two point four percent and 17.3% of subjects had the histological activity index (HAI)≥4and fibrosis (F) score≥3 respectively. Subgroup analysis showed that subjects with ALT＞0.50 × upper limit of normal (ULN) had a significantly higher rate of HAI≥4 and F score≥3 than those with ALT≤0.50×ULN (HAI≥4:36.4% vs 11.1%, χ2 =8.881, P=0.003;F score≥3:27.3% vs 9.3%, χ2 =5.487, P= 0.019, respectively), and older subjects (more than 45 years old) had a higher proportion of HAI ≥4 than the younger (33.3% vs 13.4%, χ2 =4.923, P=0.027). Multivariate Logistic regression analysis revealed that a decade increase in age was the independent predictor of HAI≥4 (OR=2.410, P=0.023).Receive operating characteristic (ROC) curve showed that 87.0% and 90.7% of subjects with ALT＜0.50× ULN had histological changes of HAI＜4 and F score＜3 respectively. The proportions of HAI≥4 and F score≥3 in subjects with HBV DNA＜1×104 copy/mL were 14.9% and 12.8%, respectively. Conclusions Significant histological changes may be present in part of the subjects with persistently normal ALT and different HBV DNA levels, so that liver biopsy is very important, especially in those with age ＞45 years.Half time the ULN may serve as an appropriate cutoff value of normal ALT level for managing Chinese HBeAg-negative chronic HBV-int'ected patients.

Objective To explore the expressions of circulating microRNAs (miRNAs) in acute liver failure mice induced by D-galactosamine (GalN)/lipopolysaccharides (LPS) and the correlation with miRNAs in the liver.Methods Forty clean grade Balb/C mice,with 32 in the model group and 8 in the control group were enrolled in the study.Liver failure was induced by intraperitoneally injection of D-GalN and LPS in mice of the model group,while mice of the control group were intraperitoneally injected with 1 mL 0.9 ％ sodium chloride solution.Serum and liver samples were collected at 0,3,5,7 hours following administration,and eight mice should be supplied to each sample,and changes of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and histopathology of the liver were observed.miRNA from both the serum and the liver was extracted,miRNA expression profile in the liver at 0,5,7 hours by locked nucleic acid (LNA)-miRNA microarray was analyzed and miRNA by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) was detected.Means of the two groups were compared using one-way ANOVA and correlation analyses were performed using Pearson and Spearman correlation.Results Expression of miRNAs in the liver tissue changed significantly over time with the occurrence of acute liver failure in the mice.Twenty-one miRNAs were up-regulated and 27 were down-regulated,among which miRNA-122 and miRNA-1187 were down-regulated while miRNA-146a and miRNA-155 were up-regulated.It was confirmed by the PCR assay that the expression of miRNA-122 and miRNA-1187 in the liver gradually decreased,while those in the serum were up-regulated over time.However,the expressions of inflammation associated miRNA-155 and miRNA-146a were up-regulated both in the serum and the liver after administration.The expressions of miRNA-122 and miRNA-1187 were negatively correlated between serum and liver (r=-0.477,P=0.0089,r=-0.420,P=0.231),while the expressions of miRNA-155 in serum and liver were positively correlated (r=0.678,P=0.0001).Moreover,the expressions of miRNA-122 (r=0.571,0.554) and miRNA-1187 (r=0.471,0.542) were also positively correlated with serum levels of ALT and AST (all P＜0.05).Liver and serum levels of miRNA-122 and miRNA-1187 changed significantly at 5 hours after administration,which preceded the changes of ALT/AST.Conclusions The expressions of miRNA-122 and miRNA-1187 in serum are well inversely correlated with the corresponding expressions in liver tissues during acute liver failure in mice.The changes of miRNA-122 and miRNA-1187 in the serum precede those of ALT/AST.These data suggest that serum miRNA-122 and miRNA-1187 might be the candidate serum biomarkers for early prediction of liver injury.

ObjectiveTo investigate the histological features as well as the factors influencing liver disease progression in Chinese patients with chronic hepatitis C (CHC). MethodsA total of 102 CHC patients who underwent percutaneous liver biopsy between August 2007 and May 2010 were recruited. Age, gender, body mass index (BMI) and transmission route of recruited patients were recorded. Serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), HCV genotypes, HCV viral load and liver histological changes were detected. Statistical analysis was done by t test and Logistic regression. ResultsThe serum levels of ALT and AST in CHC patients with histological activity index (HAI) ≥4 were much higher, while platelet (PLT) counts were lower than those with HAI ＜4(t=2.209, 2. 298 and 2. 565, respectively; all P＜0.05). Likewise, in patients with F≥3, the serum levels of ALT and AST as well as the mean age and the duration of infection were significantly elevated compared with F ＜ 3 group ( t = 3.497, 2. 758, 2. 340 and 2. 570,respectively; all P＜0. 05), while PLT counts were much lower (t = 2. 761, P=0. 007). The unvariate predictors for HAI≥4 were female, ALT＞1 × upper limits of normal (ULN), AST level,F≥3, HCV RNA≥6 lgIU/mL and PLT counts. By mutivariate analysis, the Ishak stage score was the only independent predictor for HAI≥4 (OR 3.098, 95％CI 1.884-5. 092; P＜0.01). Finally,the univariate predictors for F≥3 were age, BMI≥24 kg/m2 , ALT＞1 × ULN, AST level, HAI≥4,PLT counts and duration of infection≥ 15 years. Multivariate analysis revealed that age (OR 1. 074,95％CI 1.006-1. 146; P=0.033), ALT level (OR 1. 035, 95％CI 1.015－1.055; P＜0.01), ASTlevel (OR 0. 969, 95％CI 0. 948－0. 990; P=0. 005), the duration of infection ≥15 years (OR 37. 215, 95％CI 5. 816－238. 127; P＜0.01) and HAI≥4 (OR 1. 939, 95％CI 1. 426－2. 636; P＜0.01) were independent predictors for F≥ 3. ConclusionAge, ALT level, AST level, duration of infection≥15 years, HAI≥4 are independent predictors for liver fibrosis.

Objective To investigate the expressions of microRNAs (miRNA) and cytokines in the peripheral blood mononuclear cells (PBMCs) of patients with hepatitis B virus (HBV) infection and analyze their relationship with inflammation. Methods PBMCs were collected from acute hapatitis B (AHB) patients of 3 groups, including acute episode, virus clearance, recover period, and chronic hepatitis B (CHB) of mild, medium, severe type, and HBV-related liver cirrhosis. Each group included 20 patients, and 17 healthy donors were as control. Reverse transcription-polymerase chain reaction was used to measure miRNA146, miRNA155, miRNA181, interferon (IFN)-α, IFN-β,interferon induced gene 54 (ISG54) and interferon regulate factor 5 (IRF5). Comparisons among groups were done by one factor analysis of variance. Results The expression of miRNA155 was high in acute episode of AHB (2. 386± 1. 835), and higher than healthy control (1. 498± 1. 276) (F=1. 137,P-=0. 045), while reduced in acute episode, virus clearance (1. 633±2. 291), and recover period (0. 642±0. 836) (F=2. 122,P=0. 022). The expressions of IFN-α and IFN-β in AHB reduced in acute episode, virus clearance and recover period ( F = 1. 880, P = 0. 038 ; F= 1. 835, P = 0. 048).The expression of miRNA155 in AHB is closely correlated with IFN-α and IFN-β (r = 0. 483, P=0. 004; r= 0. 660, P= 0. 0002, respectively). In addition, in HBV infectious patients, the expression of miRNA155 was correlated with alanine transarninase (ALT), serum bilirubin (TBil) (r=0. 342,P=0. 006; r=0. 322, P= 0. 011, respectively), but not with HBV DNA load. Compared with healthy control (1. 307+ 0. 935), miRNA181 was higher in patients with HBV infection (F= 2. 072, P=0. 045) except AHB in recover period (1. 873±0. 998). There was no statistical difference in the miRNA146 expression between various groups. Conclusions The exprossion of miRNAs might be involved in the host anti-HBV immune response during HBV infection, and closely correlated with expression of IFN-related immune factors.

OBJECTIVETo investigate the changes in circulating plasmacytoid dendritic cells (pDCs) in patients with chronic hepatitis B (CHB) during the course of treatment with pegylated-interferon alfa-2s (peg-IFNa-2a) and to determine the correlations with therapeutic response.

METHODSForty-one patients with CHB who were receiving peg-IFNa-2a antiviral treatment for 48 weeks were enrolled in the study.Expression of the Toll-like receptor 9 (TLR9) on and frequency and functionality of the pDCs were analyzed at treatment weeks 0, 2, 12, 24, 36 and 48.

RESULTSAll patients exhibited an initially rapid decrease in the numbers of circulating pDCs and showed CpG-induced endogenous IFNa production within the first 2 weeks of treatment.Subsequently, all responders displayed a continuous increase in pDC numbers as well as functionality, both of which peaked around week 12 of treatment; in addition, these treatment responses were accompanied by significantly increased levels of type 1 T helper cytokines (P less than 0.05), which did not occur in the non-responders.

CONCLUSIONpDCs are involved in the initial therapeutic immune response stimulated by peg-IFNa-2a treatment.Recovery of blood pDC number and functionality may represent a predictor of favorable response to peg-IFNa-2a antiviral treatment in patients with CHB.

Objective To provide clues for the study on the mechanism of autoimmune liver disease (AILD) by exploring the existence of specific bacteria in liver tissues of AILD patients.Methods From August 2017 to August 2018,at Department of Gastroenterology arnd Hepatology,Tianjin Medical University General Hospital,a total of 12 patients diagnosed as AILD (four autoimmune hepatitis (AIH),four primary biliary cirrhosis (PBC) and four PBC-AIH overlap syndrome (OS)) and four patients with hepatic cyst (control group) were enrolled and all the patients underwent liver biopsy.16S rRNA gene sequencing was carried out in the obtained aseptic liver tissues.Linear discriminant analysis effect size was used to find out the specific bacteria.Spearman correlation analysis was performed to analyze the correlation between the liver microbiota and the disease.The metabolic function of the 16S rRNA gene sequences was also predicted.Results Bacteria were detected in the liver tissues of all the 16 patients.At the species level,the abundance of Planococcus rifietoensis of AIH group was 0.100％,which was higher than those of other three groups (0),and the difference was statistically significant (linear discriminant analysis (LDA) =3.31,P =0.034).The abundance of Anoxybacillus flavithermus of PBC group was 0.200％,which was higher than those of other three groups (0.100％),and the difference was statistically significant (LDA =3.34,P =0.014).The abundance of Pseudomonas aeruginosa PAO1,Bacillus firmus,Brevibacillus agri,Acinetobacter baumannii,Sphingomonas zeae and Salmonella enterica were significantly negatively correlated with serum level of γ-glutamyl transferase (r=-0.68,-0.68,-0.67,-0.68,-0.68 and-0.66,all P ＜0.01).Compared with that of the hepatic cyst group,the lipid metabolism of AILD patients decreased.The levels of serum low density lipoprotein and total cholesterol were significantly negatively correlated with the biosynthesis of unsaturated fatty acids (r =-0.55 and-0.65,both P ＜ 0.05).Conclusions There exist specific bacteria in the liver tissues of AIH and PBC groups.The liver microbiota which is closely related with the pathogenesis of AILD might be a potential therapeutic target and diagnostic biomarker.