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Zhi Xia Dong,
Hui Juan Zhou,
Jian Hua Wang, Xiao Gang Xiang,
Yan Zhuang,
Si Min Guo,
Hong Lian Gui,
Gang De Zhao,
Wei Liang Tang,
Hui Wang,
Qing Xie
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ABSTRACT: This study aimed to explore the most up-to-date distribution of hepatitis C virus (HCV) genotypes in China, especially the association between HCV genotypes and patients' characteristics and clinical parameters.
Sera from 483 HCV antibody-positive patients were genotyped using a HCV genotyping chip assay. The distribution of HCV genotypes, clinical parameters, modes of transmission and duration of infection were determined and the relationships among these parameters were analyzed.
A total of 424 patients were successfully genotyped. HCV genotypes 1, 2, 3 and 6 were found with a constituent ratio of 72.1%, 12.3%, 10.6% and 5.0%, respectively, in which subtypes 1b (69.1%), 2a (11.6%) and 3a (7.5%) were prevalent. The mean age of patients with genotype 1 and 2 was significantly elder than those with genotype 3 and 6 (P < 0.05). The distribution of HCV genotypes in relation to the mode of HCV transmission was remarkable (P < 0.001). Transfusion of blood and blood products was the main mode of transmission. Most genotype 1 infection (53.1%) was found in the group with a duration of HCV infection of 10-20 years. Genotype 1b was independently associated with age (P = 0.001) and mode of HCV transmission (P = 0.007).
The main HCV subtype was genotype 1b in Chinese patients. The prevalence of HCV genotypes was correlated with age and the mode of HCV transmission. Genotype 3a and 6 may become an increasing threat in the future.
Journal of Digestive Diseases 11/2012; 13(11):564-70. · 1.59 Impact Factor
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ABSTRACT: In the current study, we aimed at elucidating the regulatory mechanisms through which microR-1187 (miR-1187) participates in hepatocyte apoptosis in acute liver failure (ALF). An ALF model was induced with D-galactosamine (D-GalN) plus lipopolysaccharide (LPS) in BALB/c mice. The hepatic miRNA expression profile was detected by microarray analysis and verified by quantitative real-time PCR (qRT-PCR). The possible underlying mechanism was investigated in vitro using an embryonic murine hepatocyte cell line (BNLCL2) and miR-1187 mimic. Caspase-8 protein was detected by Western blotting and cell apoptosis was assayed by flow cytometry. Hepatic miR-1187 was down-regulated in ALF mice based on microarray data (P<0.001) and verified by qRT-PCR (P<0.01). Target scan revealed that caspase-8 was the putative target of miR-1187. In an in vitro study, miR-1187 showed the highest up-regulation in BNLCL2 cells transfected with the miR-1187 mimic at a 50 nM concentration for 12 h compared with cells transfected with the non-specific mimic (P<0.001). miR-1187 was down-regulated (P<0.01) but caspase-8 mRNA (P<0.01) as well as protein (P<0.05) were up-regulated in the BNLCL2 cells treated with D-GalN/TNF. Furthermore, overexpressed miR-1187 reduced caspase-8 expression at both the mRNA and protein levels significantly (P<0.01 and P<0.05 respectively), and significantly attenuated the apoptotic rate of BNLCL2 cells (P<0.05). We show that miR-1187 regulates hepatocyte apoptosis by targeting caspase-8. miR-1187 may serve as a potential therapeutic target for the treatment of ALF.
International Journal of Molecular Medicine 04/2012; 29(4):663-8. · 1.98 Impact Factor
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ABSTRACT: To explore the categories of drugs causing hepatotoxicity and analyze the clinical and histological features of the corresponding drug-induced liver injury (DILI), in order to gain insights into potential diagnostic factors for DILI.
A total of 138 DILI patients treated at our hospital from April 2008 to April 2010 were retrospectively analyzed. The responsible drug for each DILI case was recorded. The Roussel Uclaf Causality Assessment Method (RUCAM) had been used to diagnose DILI. Only cases that had scored as highly probable or probable (more than or equal to 6 points by RUCAM) were included in this study. The patients' general condition, clinical manifestations, and serum biochemical and immunological parameters were assessed. Sixty-six of the patients underwent liver biopsy, and were assessed for liver pathological changes. Clinical and laboratory test data were collected and used to classify the total 138 cases as hepatocellular injury, cholestatic, or mixed hepatocellular-cholestatic types.
Within our patient population, the leading cause of DILI was Chinese herb medicine, accounting for 53.62% of cases. Antibiotics were implicated in 7.97% of cases, and dietary supplement in 6.52% of cases. Correlation between the clinical features and histological injury pattern was stronger at the time of biopsy (more than or equal to 3 days after laboratory results) (kappa = 0.63, P less than 0.05) than at the onset of DILI (kappa = 0.25, P less than 0.05). All modified hepatic activity index (HAI) necroinflammatory scores and fibrosis scores were more severe in the cholestatic and mixed injury types than in the hepatocellular injury type (P less than 0.01 and P less than 0.05, respectively).
Chinese herbal medicine, dietary supplements and antibiotics were the main causes of DILI in our patient population. The clinical and histological features correlated well, especially at later stages of DILI. The degree of inflammation and fibrosis was significantly higher in cholestatic and mixed hepatocellular-cholestatic injury types than in the hepatocellular injury type. Assessment of both clinical and pathological features may represent a more accurate diagnostic method for DILI.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 03/2012; 20(3):185-9.
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Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 07/2010; 18(7):491-4.
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ABSTRACT: Hepatitis C virus (HCV) infection is still a major global health issue despite decades of research. The liver-specific microRNA-122 (miR-122) can stimulate HCV replication/translation in vitro, indicating that miR-122 contributes to pathogenesis of HCV. However, it remains controversial whether interferon (IFN) inhibits HCV via modulating miR-122 expression. The underlying mechanism of ribavirin (RBV) in enhancing IFN treatment for HCV patients has yet to be explored. We investigated the relationship between miR-122 expression and anti-HCV activity of IFN beta in combination with RBV in vitro, due to difficulty accessing an HCV animal model. Upregulation of ISG54 mRNA or cytostatic effect was detected in Huh7 and HCV replicon cell lines in response to IFN beta or RBV stimulation, respectively. It was found that IFN beta and/or RBV suppressed miR-122 expression marginally, with a synergetic anti-HCV effect between IFN beta and RBV. Marginal modification of other miRNAs was also observed in these cell lines, using miRNA array following IFN beta and RBV treatment. Taken together, our data suggest that miRNAs are not crucial in anti-HCV action, following IFN beta and/or RBV stimulation in vitro.
International Journal of Molecular Medicine 06/2010; 25(6):853-9. · 1.98 Impact Factor
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ABSTRACT: To establish a convenient realtime PCR which can detect microRNAs in the human hepatoma cell line, Huh7 cells.
Total RNAs in Huh7 cells were extracted. MicroRNA 122, 24 and 146a were assayed by microRNA array, and then verified by Northern blot. Stem-loop RT-PCR and poly(A)-tailed RT-PCR were used to detect the above microRNAs. Data were analyzed with Quantity One software and 7500 system software.
Microarray signal intensity of microRNA 122, 24 and 146a in Huh7 cells was 2201.49, 410.20 and 4.70, whose relative expression was confirmed as 0.0383, 0.0249, 0.0001 through Northern blot. While the poly(A)-tailed RT-PCR might only measure microRNA 122, Stem-loop RT-PCR could detect microRNA 122, 24 and 146a, whose average dCt was 2.5, 5.8 and 12.1 in accordance with microRNA array and Northern blot.
Stem-loop RT-PCR can specifically and sensitively quantity microRNA levels, regardless of their abundance.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 09/2009; 17(8):603-6.
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ABSTRACT: The renin angiotensin system (RAS) plays a major role in liver fibrosis. A novel homologue of angiotensin converting enzyme, ACE2, was identified as a negative regulator of RAS as it degrades Ang II to Ang1-7. We investigated in vivo the expression of ACE2 in liver fibrosis. We evaluated the relationship between biochemical variables and liver tissue expression of ACE2, the correlation between a histological assessment of liver fibrosis and liver tissue expression of ACE2. Male SD rats were randomly divided into a CCL4 group which received injections of CCL4 and the control group which received injections of olive oil. Liver pathology was examined by H&E and Sirius red staining, and real-time PCR was performed to determine the gene expression levels of ACE2 and ACE. Real-time PCR analysis revealed that ACE2 mRNA was higher at the two-, four-, and six-week time points, respectively (p<0.01). Similarly, hepatic ACE mRNA was significantly increased after CCL4 injection. There was a significant correlation between ACE and ACE2 gene expression (r=0.750, P<0.001). ACE2 gene expression strongly correlated with ALT (r=0.669, P<0.0001) and AST levels (r=0.815, P<0.0001). There was a significant correlation between circulating ACE2 and histological scores of liver fibrosis. ACE2 and ACE gene expression correlated with the ISHAK score (r=0.850, P<0.001; r=0.806, P<0.001). There was a significant relationship between ACE2 gene expression and the degree of liver fibrosis. ACE2 plays a crucial role in liver fibrogenesis.
International Journal of Molecular Medicine 06/2009; 23(6):717-23. · 1.98 Impact Factor
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Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 10/2008; 16(9):704-5.
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Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 10/2006; 14(9):682-4.
