Role of heat shock protein 90 in hepatitis B virus replication / 临床肝胆病杂志

Hepatitis B virus （HBV） has the characteristics of wide transmission， a high chronic infection rate， and a low cure rate， and improving the cure rate of HBV may help to improve the long－term prognosis of patients. Heat shock protein 90 （Hsp90） is a chaperone protein widely present in organisms. In recent years， more and more studies have shown that Hsp90 is associated with HBV infection and plays an important role in HBV replication. It can not only interact with specific proteins of the virus to promote its replication， but also interact with the host’s own proteins to perform its function. This article reviews the role of Hsp90 in HBV replication in recent studies， so as to provide new theoretical guidance and directions for the development of new anti－HBV drugs targeting Hsp90 and the prevention and treatment of HBV infection in the future.

Association between intrahepatic bile duct alterations and liver fibrosis / 临床肝胆病杂志

Liver cirrhosis is a liver disease caused by various factors and is characterized by diffuse fibrous hyperplasia, lobular structural damage, and pseudolobule formation. Bile duct proliferation has been observed in a variety of animal models of liver cirrhosis and patients with liver cirrhosis caused by different etiologies, and it is regulated by signaling pathways with the involvement of multiple regulatory factors such as neuropeptides, neurotransmitters, and hormones. Moreover, the proliferated bile ducts promote the formation of liver fibrosis by mediating the proliferation and activation of hepatic stellate cells. This article summarizes the changes of the intrahepatic bile duct system in liver cirrhosis and its influence on the process of liver fibrosis, various signaling pathways associated with cholangiocyte proliferation and liver fibrosis, and the value of the dynamic evolution of bile duct structure in predicting the degree of liver fibrosis. It is pointed out that bile duct proliferation may become a potential target for the intervention of liver fibrosis, which provides new ideas and methods for early treatment and reversal of liver fibrosis.

Clinical features of cholestatic liver disease of 107 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of cholestatic liver disease (CLD), and to provide a reference for strengthening the diagnosis and treatment of this disease. MethodsA retrospective analysis was performed for the clinical data of 107 patients who were admitted to Chenggong Hospital Affiliated to Xiamen University from January 2015 to December 2017 and were diagnosed with CLD. The t-test was used for comparison of continuous data between groups. ResultsMost patients had the clinical symptoms of weakness, loss of appetite, nausea, abdominal distension, pruritus, and jaundice. According to the site of cholestasis, there were 64 patients (59.8%) with intrahepatic cholestasis and 43 (40.2%) with extrahepatic cholestasis. The cause of the disease was common bile duct stones in 21 patients (19.6%), bile duct parasites in 1 patient (0.9%), primary sclerosing cholangitis in 2 patients (1.9%), primary biliary cirrhosis in 3 patients (2.8%), liver cancer in 8 patients (7.5%), bile duct carcinoma in 5 patients (4.7%), pancreatic cancer in 4 patients (3.7%), pancreatitis in 12 patients (11.2%), viral hepatitis in 28 patients (26.2%), drug-induced liver injury in 11 patients (10.3%), alcoholic hepatitis in 6 patients (5.6%), nonalcoholic fatty liver disease in 4 patients (3.7%), and autoimmune hepatitis in 2 patients (19%). The CLD patients with underlying diseases had a significantly poorer liver function (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, bile acid, and total bilirubin) than those with CLD alone (t=-3.44, -2.99, -2.42, -4.39, -3.34, and -2.49, all P＜0.05). Most of the patients achieved good recovery after liver-protecting, transaminase-lowering, and jaundice clearance treatment. The patients with tumors had poor prognosis. ConclusionCLD has various causes, and its clinical features lack specificity. Clinicians should pay enough attention to this disease.

Research advances in susceptibility genes and their role in the pathogenesis of nonalcoholic fatty liver disease / 临床肝胆病杂志

Currently the incidence of nonalcoholic fatty liver disease (NAFLD) is increasing, and the age of onset is getting younger worldwide, resulting in a heavy economic burden for both individuals and the society. Since NAFLD is closely related to heredity, metabolism, and the environment, genetic factors play an important role in the development and progression of NAFLD. With the development and wide application of the techniques from the genome-wide association studies, new research advances have been achieved in the susceptibility genes of NAFLD. This review summarizes the related research findings at home and abroad, and investigates the pathogenic factors for NAFLD and related mechanisms with a focus on the polymorphisms of susceptibility genes.

RBP2 induces stem-like cancer cells by promoting EMT and is a prognostic marker for renal cell carcinoma

Renal cell carcinoma (RCC), one of the most common kidney cancers, has a poor prognosis. Epithelial to mesenchymal transition (EMT) is a hallmark of carcinoma invasion and metastasis. Several studies have examined the molecular regulation of EMT, but the relationship between histone demethylases and EMT is little understood. In this study, we investigated the role of retinoblastoma-binding protein-2 (RBP2), a histone demethylase that is highly expressed in RCC and is positively correlated with poor RCC prognosis in the regulation of EMT. We found that ectopic overexpression of RBP2 can induce cancer stem cell-like (CSC) phenotypes through EMT in RCC cells by converting them to a more mesenchymal phenotype. This results in increased resistance to apoptosis, which leads to enhanced tumor growth in xenograft models. Together, our data show that RBP2 is an epigenetic regulator that has an important role in the initiation of CSC phenotypes through EMT, leading to tumor progression. RBP2 is also a novel biomolecule for RCC diagnosis, and prognosis and may be a therapeutic target.

Role and mechanism of action of fibroblast growth factor-21 in reducing triglyceride in nonalcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the role and mechanism of action of fibroblast growth factor-21 (FGF-21) in reducing triglyceride (TG) in the in vitro and in vivo models of nonalcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>(1) A mixture of free fatty acids was used to establish a model of steatosis in L02 cells, and the cells were treated with various concentrations of FGF-21 or fenofibrate. Twenty-four hours later, oil red O staining was performed to observe the degree of steatosis, and intracellular TG content was determined. RT-PCR and Western blot were applied to measure the mRNA and protein expression of sterol regulatory element-binding protein-1c (SREBP-1c). (2) High-fat diet was used to establish a mouse model of steatosis, and these mice were intraperitoneally injected with FGF-21 or fenofibrate. Eight weeks later, whole blood and liver samples were collected, and HE staining was performed to observe steatosis. Meanwhile, the serum levels of TG, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured, and TG content in the liver was also measured. One-way analysis of variance was used for comparison of data between multiple groups, and the least significant difference t-test was used for comparison between any two groups.</p><p><b>RESULTS</b>(1) Compared with the control group, the model group showed significant steatosis, with significant increases in intracellular lipid droplets and TG content (t = -20.57, P < 0.01), while FGF-21 reduced the number of intracellular lipid droplets and TG content (F = 98.16, P < 0.01) in a dose-dependent manner. In addition, the model group had significantly increased mRNA and protein expression of SREBP-1c compared with the control group (t = -10.73 and -0.1006, both P < 0.01), while FGF-21 down-regulated the mRNA and protein expression of SREBP-1c (F = 161.35 and 36.72, both P < 0.01). (2) Compared with the mice in the control group, those in the model group showed significant steatosis and had significant increases in serum TG level and TG content in the liver (t = -18.84 and 15.71, both P < 0.01). FGF-21 relieved hepatic steatosis and reduced the serum TG level and TG content in the liver (t = 18.11 and 9.46, both P < 0.01). Moreover, FGF-21 reduced the serum levels of ALT and AST in NAFLD mice (t = 25.93 and 12.50, both P < 0.01).</p><p><b>CONCLUSION</b>FGF-21 can inhibit the synthesis of TG through suppressing the expression of SREBP-1c, which further confirms the potential therapeutic effect of FGF-21 in the treatment of NAFLD. This may provide new ideas for the treatment of NAFLD.</p>

Association between Adiponectin polymorphisms and nonalcoholic fatty liver disease in Han Chinese popu-lation in Qingdao / 实用医学杂志

Objective To investigate the association between the Adiponectin rs266729 and rs2241766 gene polymorphisms and nonalcoholic fatty liver disease in the Han Chinese population residing in Qingdao. Methods Adiponectin rs266729 and rs2241766 gene polymorphisms were genotyped in patients with NAFLD (n = 336) and healthy controls (n = 280) using polymerase chain reaction (PCR). Serum lipid profiles and adiponectin levels were determined using biochemical methods. Statistical analyses were performed using Pearson Chi square test, logistic regression analysis, t test, linear regression analysis. Results We found a significant association between the Adiponectin rs266729 genotype frequencies and allele frequencies between NAFLD pa-tients and controls (χ2= 9.929, P = 0.007; χ2= 9.809, P = 0.002). After adjustment of confounding factor, the rs266729 G allele was associated with an increased risk of NAFLD compared to the C allele (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008) No significant differences were found in the rs2241766 genotype frequencies and allele frequencies between NAFLD population and the controls (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008). Conclusion The Han Chinese in Qingdao carrying the rs266729 G allele are at increased risk of NAFLD.

Role of SREBP-1c in risk of liver disease associated with the triacylglycerol lipase PNPLA3 I148M variant / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between SREBP-1c and the risk of liver disease associated with the triacylglyceride lipase PNPLA3 I148M variant using a human hepatoma cell line model transfected with recombinant lentiviruses.</p><p><b>METHODS</b>Huh7 cells were transfected with control lentivirus or lentivirus containing the PNPLA3 I148M variant (variant). The two cell groups were compared to assess differences in triglyceride content (using oil red O staining), levels of triglyceride and cholesterol (using automated biochemical analyzer), expression of SREBP-lc mRNA (using fluorescence quantitative PCR), and expression of SREBP-1c protein (using western blot.</p><p><b>RESULTS</b>Cells expressing the PNPLA3 I148M variant showed higher triglyceride content (0.54+/-0.03 mmol/L vs. control cells: 0.23+/-0.02 mmol/L; t=22.58, P<0.001), cholesterol level (0.28+/-0.03 mmol/L vs. control cells: 0.13+/-0.02 mmol/L; t =11.83, P<0.001), SREBP-1cmRNA expression (13.59+/-0.60 vs. 11.81+/-0.82; [The abstract and text in the paper say variant increases, but the data shown says the higher value is in the control cells. Please correct to properly express the data.] P=0.001), and SREBP-1c protein expression. The level of SREBP-1c was positively correlated with serum triglyceride in the cells expressing the PNPLA3 I148M variant (r=0.912, P<0.01).</p><p><b>CONCLUSION</b>The risk of liver disease associated with the PNPLA3 I148M variant, which increases lipogenesis, may involve SREBP-1c and a pathway that increases triglycerides.</p>

I148M polymorphism of PNPLA3 gene affects cell cycle of hepatoma carcinoma cell Huh-7 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the cell cycle of Huh-7 cells affected by I148M polymorphism of PNPLA3 gene and the possible mechanisms.</p><p><b>METHODS</b>Huh-7 cells which could respectively overexpress PNPLA3 wild type and I148M variant were cultured and Huh-7 cells with zero load plasmids were used as matched control, Flow cytometry was conducted to detect the cell cycles of these 3 type of Huh-7 cells and western blot and realtime fluorescence quantitative PCR were applied to investigate the expression of regulatory factors (Cyclin D1 and p53) of cell cycle. t-test was used in statistical analysis.</p><p><b>RESULTS</b>Cell cycle phase distribution was presented by the proportion of cells in each phases (%), compared with the control group, the cell cycle phase distribution (G1 phase 59.27 ± 0.15, G2/M phase 24.23 ± 0.31, S phases 16.50 ± 0.26) had no differences in wild type group (G1 phase 58.53 ± 0.35, G2/M phase 24.87 ± 0.60, S phases 16.60 ± 0.26; Probability value less than 0.05). While between variant type group and wild type group, G1 phase was significantly decreased (variant type group G phase 38.37 ± 0.21, Probability value less than 0.05), S phase and G2/M phase were increased (variant type group S phase 27.47 ± 0.35, P less than 0.05; G2/M phase 34.17 ± 0.15, P less than 0.05), respectively. compared with control group, the relative expression of P53 mRNA in variant type group was significantly upregulated (control group 1.06 ± 0.41, variant type group 6.54 ± 0.34; Probability value less than 0.05) and there was no statistical significance in wild type group (1.66 ± 0.30, P more than 0.05); Cyclin D1 expression showed no statistical significance in any of these three groups, control group 1.00 ± 0.10, wild type group 1.06 ± 0.03, variant type group, 1.11 ± 0.04; P > 0.05).</p><p><b>CONCLUSION</b>I148M polymorphism of PNPLA3 gene affects cell cycles of Huh-7 cells via up-regulatating P53.</p>

Association between the PNPLA3 I148M polymorphism and chronic hepatitis B in a Qingdao Han Chinese population / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the association between the PNPLA3 rs738409 polymorphism and chronic hepatitis B (CH[B) in a Han Chinese population residing in Qingdao.</p><p><b>METHODS</b>Peripheral blood samples were collected from 185 CHB patients and 164 healthy controls and subjected to polymerase chain reaction (PCR) and DNA sequencing to determine the PNPLA3 genotypes. The relative risk of the rs738409 polymorphism for CHB was estimated by calculating the odds ratio (OR) and 95% confidence interval.</p><p><b>RESULTS</b>The rs738409 G allele frequency was significantly different between the CHB and control groups (31.9% vs.21.9% respectively, P less than 0.05). Compared to he rs738409 C allele, the G allele was associated with an increased risk of developing CHB (OR =1.67, 95% CI:1.18-2.34, P =0.003). Logistic regression model analysis, with adjustment for confounding factors, indicated that carriers of the PNPLA3 rs738409 GG + GC genotype had increased risk of CHB than carriers of the CC genotype (OR =1.76 ,95% CI:1.14-2.71, P =0.011).</p><p><b>CONCLUSION</b>Qingdao Han Chinese who are carriers of the rs738409 G allele are at increased risk of CHB.</p>

Association between APOC3 promoter region polymorphisms and non-alcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the association between two polymorphisms of the APOC3 gene (T-455C and C-482T) and hereditary risk of non-alcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>A total of 287 patients with NAFLD and 310 control subjects were genotyped by PCR and direct sequencing. Serum lipid profiles were also detected by standard biochemical</p><p><b>METHODS</b>One-hundred-and-eighty of the study participants were used to measure the APOC3 content by enzyme-linked immunosorbent assay. Inter-group differences and associations were assessed statistically using Chi square and t tests and logistic and linear regression analyses.</p><p><b>RESULTS</b>The frequencies of neither the genotypes or alleles were significantly different between the NAFLD cases and the controls. Compared with the most common genotypes-455TT or-482CC, none of the variants showed a significant increase in risk of NAFLD or for the clinical and biochemical parameters. The adjusted odds ratios (with 95% confidence intervals) of NAFLD were 1.25 (0.79-1.96) and 1.20 (0.76-1.89) for carriers of the APOC3-455C and-482 T variants respectively (P more than 0.05).</p><p><b>CONCLUSION</b>The T-455C and C-482T polymorphisms of the APOC3 gene are not associated with risk of NAFLD, pathogenic changes in lipid profiles, or insulin resistance in Han Chinese.</p>

Creation of a special medical service mechanism for large international sport events / 中华医院管理杂志

For medical service provision for the Olympic Games, a special medical service mechanism for important international sport events eventually took shape, based on task analysis and medical services provided in test games for two years including 2006 and 2007 Qingdao Sailing Regatta. This mechanism features the following: First, "7-Special" sport event medical practice - Medical zones, medical teams, service flows, service signs, medical papers, and drug management, all exclusively earmarked for the event; Second, medical services up to international standard; Third, special flows for medical rescue; Fourth, Special system for information reporting. Thanks to this special mechanism, the hospital provided its medical assurance for the Olympic Games successfully, and upgraded its routine medical services as a result.

Study of the relationship between HAI and HBsAg,HCV expression in HCC,pericarcinomatous tissues with immunohistochemistry / 中华传染病杂志

Objective To study the relationship between HAI and HBsAg, HCV in HCC, pericarcinomatous tissues. Methods The patterns of HBsAg and HCV in 100 cases of hepatocellular carcinoma(HCC) and their surrounding liver tissues were studied on paraffin-embeded sections with immunohistochemistry technique, and pericarcinomatous tissues were scored in Knodell’s histological activity index(HAI). Results The score of HAI in the group of co-infection of HBV, HCV is the highest in the four groups(12.62?3.88). The score of HAI in the group which is not infected by HBV, HCV is the lowest in the four groups(6.67?2.58). HBV, HCV virus infection were positively correlated with HAI(rs=0.39,P=0.0001). HBsAg and HCV were detected both in HCC and pericarcinomatous tissues. The positive rate of HBsAg in Pericarcinomatous Tissues(79%) was higher than that of in HCC tissues(23%). HCV expressions in HCC(15%) and pericarcinomatous tissues(23%) had no differences. Conclusions As for the tissues of liver cancer with virus infection background, the HAI is obviously higher than that without virus infection background. HBV, HCV virus infection were correlated with HAI significantly, perennial virusemia will aggravate pathological changes of liver tissue.