Taurine alleviates high-fat-high-glucose-induced pancreatic islet ß-cell oxidative stress and apoptosis in rat.

The effect of taurine (TAU) as a specific regulatory mediator on pancreatic function in obese rats induced by a high-fat-high-glucose (HFHG) diet was investigated. We fed male Sprague-Dawley rats under different conditions, namely the control, HFHG, TAU, and HFHG + TAU treatment groups for 4 months. Compared with the HFHG group, TAU supplementation significantly reduced malondialdehyde levels and increased superoxide dismutase, total antioxidant capacity, and glutathione levels in the rat pancreas. In addition, TAU significantly decreased the level of reactive oxygen species, and markedly increased the activity of heme oxygenase 1 (HO-1), Kelch-like ECH-associated protein 1 (KEAP-1), and nuclear factor erythrocyte-2-related factor 2 (Nrf2) in the rat pancreas. Notably, HFHG diet could induce pancreatic injury in the rats through the Nrf2/HO-1 signaling pathway and activate the mitochondrial channel-mediated apoptotic signaling pathway. The addition of TAU significantly improved the pancreatic tissue injury induced by the HFHG diet in the rats and reduced the protein expression of Caspase-3, Cleaved-caspase-3, Caspase-9 and Bcl-2 associated protein X (BAX), and increased the protein expression of B-cell lymphoma-2 (Bcl-2). In conclusion, this experiment confirmed that TAU could alleviate the oxidative stress and apoptosis induced by the HFHG diet in rat pancreatic ß-cells.

Dynamic changes of lymphocytes and the disease progression in patients with coronavirus disease 2019 in Xi’an / 西安交通大学学报(医学版)

【Objective】 To analyze the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) in Xi’an so as to investigate the relationship between the dynamic changes of lymphocytes and the disease progression. 【Methods】 We retrospectively analyzed the clinical data of 15 patients with COVID-19 in The First Affiliated Hospital of Xi’an Jiaotong University from January 22 to February 16, 2020. 【Results】 Among the 15 patients with COVID-19, 8 were males and 7 were females, aged from 22 to 89 years. There were 12 ordinary cases (80%), 1 severe case (6.67%), and 2 critical cases(13.33%). There were 6 groups of family clusters.Most of the patients (14/15, 93.3%) had fever of different degrees. The average time from illness onset to admission was 2.80±1.66 days, and the average time from illness onset to diagnosis was 2.83±2.29 days. The main accompanying symptoms were dry cough (8/15, 53.33%) and shortness of breath (4/15, 26.67%). Nine patients (60%) who had low lymphocyte counts at admission, including of all of the critically ill patients (1 severe case and 2 critical cases) and 6 (6/12, 50%) ordinary patients. Lymphocyte counts in the ordinary cases increased gradually, but fluctuated in the severely ill patients. They were always at low level, or even decreased overall in critical cases. 【Conclusion】 In Xi’an City, COVID-19 mostly occurred in family clusters. Lymphocyte counts were reduced in most patients, especially in critically ill (severe and critical) ones. The lymphocyte count at admission and its kinetics during therapy may be an important predictor for the severity and prognosis of the disease.

The regulation mechanism of HCBP6 mimic phosphorylation on triglyceride synthesis in hepatocytes / 西安交通大学学报(医学版)

【Objective】 To investigate the regulation of HCBP6 mimic phosphorylation on triglyceride synthesis in hepatocytes so as to provide a molecular target for the treatment of metabolism-associated fatty liver disease. 【Methods】 We used site-directed mutagenesis to mimic constitutive phosphorylation and dephosphorylation of HCBP6 Ser-10 and Ser-151. Oil red O staining and triglyceride content determination were used to detect triglyceride levels in hepatocytes. The expressions of SREBP1c, ACC1 and FASN were detected by qRT-PCR and Western blotting. The Dual-Luciferase Report Gene System was used to detect SREBP1c promoter activity. 【Results】 HCBP6 Ser-10 phosphorylation promoted triglyceride synthesis. HCBP6 Ser-10 phosphorylation upregulated the expressions of SREBP1c, ACC1and FASN genes; HCBP6 Ser-10 phosphorylation enhanced the SREBP1c promoter activity. 【Conclusion】 HCBP6 Ser-10 phosphorylation can significantly enhance the activity of the SREBP1c promoter, upregulate the SREBP1c-FASN signal pathway transduction, and promote the synthesis of triglycerides.

Efficacy and safety of paritaprevir/ritonavir/ombitasvir combined with dasabuvir in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection: a randomized, double-blind, placebo-controlled study - China data / 中华肝脏病杂志

Objective@#To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily combined with dasabuvir 250mg, twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection. @*Methods@#A randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial was conducted in mainland China, Korea, and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated (interferon alpha /pegylated interferon alpha) and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection. Patients randomly received OBV/PTV/r plus DSV for 12 weeks (Group A), or placebo for 12 weeks (Group B) followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks. Sustained response (SVR12) rate obtained at 12 weeks and (SVR24) 24 weeks after discontinuation of treatment, and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed. @*Results@#A total of 410 cases of Chinese patients were included and randomly assigned to group A and B (with 205 cases in each group) in a 1:1 ratio. The rates of SVR12 and SVR24 were 99% (95% CI: 94.8% - 99.8%) in the newly diagnosed patients in group A (205 patients) and the rates of SVR12 and SVR24 were 100% in treated patients (95% CI: 96.3% - 100%). Different baseline characteristics had no effect on SVR12 and SVR24 rates. Most of the adverse events occurred were mild, asymptomatic, and≥ 3 laboratory abnormalities during treatment were rare, including elevation of alanine aminotransferase (2 cases in double-blind stage A group), aspartate aminotransferase (Double-blind stage A (3 cases) and total bilirubin (1 case in open-label phase B group); however, those mild adverse events could be recovered after drug withdrawal or discontinuation. only1 person discontinued drugs due to adverse events (Group B, open-label phase). @*Conclusion@#The 12 weeks treatment course of OBV/PTV/r combined with DSV produced 99% ~ 100% rates of SVR12 and SVR24 in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection, and the tolerance and safety were good.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin in Asian adult patients with chronic HCV genotype 1b infection and compensated cirrhosis / 中华肝脏病杂志

Objective@#To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. @*Methods@#An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. @*Results@#A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. @*Conclusion@#Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.

Effects of thymosin α1 on plasma TNF-α and IL-10 of rats with acute liver failure / 西安交通大学学报(医学版)

Objective To investigate the effects of thymosin α1 (Tα1) on plasma TNF-α and IL-10 of rats with acute liver failure.Methods The model of acute liver failure in rats was established.The rats in intervention group were injected with Tα1;their plasma ALT, AST and TBIL contents as well as plasma TNF-α and IL-10 levels were assayed at different time points for HE staining of liver sections.Results ① ALT, AST and TBIL in model group and intervention group increased over time.Plasma ALT, AST and TBIL were significantly lower in intervention group than in model group at the same time point (P<0.05).② Manifestations of acute liver failure such as structural disorder of liver tissue, obvious necrosis of liver cells and infiltration of inflammatory cells were observed in model group and intervention group, and worsened over time.At the same time point, liver cell necrosis and infiltration of inflammatory cells were less severe than those in model group.③ TNF-α and IL-10 were significantly higher in model and intervention groups than in control group (P<0.05).Plasma TNF-α and IL-10 showed a rising trend over time in the former groups (P<0.05).At the same time point, TNF-α was significantly lower but IL-10 was significantly higher in intervention group than in model group.Conclusion Thymosin α1 has a protective effect on acute hepatic failure in rats, and it can significantly alleviate liver inflammation and necrosis.The mechanism is related to inhibition of pro-inflammatory cytokine TNF-α and upregulation of anti-inflammatory cytokine IL-10.

Verification of the interaction between ASGPR and HBV preS1 protein / 西安交通大学学报(医学版)

Objective To verify the interaction between asialoglycoprotein receptor (ASGPR)and hepatitis B virus (HBV)preS1 protein in vivo and in vitro ,and identify ASGPR as a cell-surface receptor for HBV,which could elucidate the molecular mechanism of HBV infection.Methods The preS1-ASGPR interaction was examined in mammalian two-hybrid and coimmunoprecipitation system by strictly following the manufacturer’s instructions.Results ASGPR interacted specifically and directly with the preS1 domain of HBV in vivo and in vitro .Conclusion ASGPR may be a candidate receptor for HBV that mediates further step of HBV entry.

Research advances in paternal-fetal vertical transmission during HBV infection / 临床肝胆病杂志

Hepatitis B virus (HBV) infection is a global public health problem which greatly threatens human health. Paternal-fetal vertical transmission (P-FT) is one of the leading causes of persistent HBV infection, and has a transmission rate similar to that of mother-to-child vertical transmission. In recent years, P-FT has been attracting more and more attention and has become a hot research topic at home and abroad. It has been confirmed that P-FT occurs via sperm, but the mechanism remains unknown. Studies have shown that a high HBV DNA load in serum and semen and positive serum HBeAg are the major risk factors for the occurrence of P-FT. Random integration of HBV DNA into sperm can affect sperm quality, cause male infertility, and even affect the maternal pregnancy outcome. Currently the most important measure to block P-FT is pre-pregnancy intervention, including antiviral therapy for the father and active immunization for the mother.

The development and transplantation of LCD module-based interface for medical diagnosis instrument / 中国医疗器械杂志

Based on LCD Module and Visual C++ development environment, this paper proposes a new method which can quickly develop the human-machine interface .We define a LCD module programming interface by designing Serial Communication Class(SCS). On this basis,we achieve the transplantation on an Embedded ARM Platform to fulfil the requirements of Medical Diagnostic Instruments (MDI). Experimental results show that this method has advantages of short development cycle and high level transplantation which has broad application prospects in the field of Medical Diagnosis Instrument.

Proapoptotic IL-18 in patients with chronic hepatitis C treated with pegylated interferon-alpha.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. In mainland of China, It was estimated the population of 1.3 billion infected with HCV. HCV is not cytopathic. Immune response that is essentially conducted by cytokines may play an important role in the pathogenesis of HCV infection. Interleukin (IL)-18, mainly produced by monocytes/macrophages, plays an important role in the immune system by enhancing T cell responses, regulating interferon-gamma (IFN-gamma) production and promoting the development of T helper cell Th1 immune responses. Raised serum levels of IL-18 have recently been reported in patients with chronic hepatitis C before antiviral therapy. Herein we report the IL-18 sequential changes in patients with hepatitis C during the period of pegylated interferon (PEG-IFN) alpha treatment for 48 weeks. We established the correlation of plasma IL-18 level and alanine aminotransferase (r = 0.77, P < 0.05). Hepatic inflammatory activity in chronic hepatitis C was shown to be closely associated with an increased amount of IL-18. HCV-infected patients had raised IL-18 levels (93.67 +/- 23.58 pg/ml versus 59.73 +/- 24.06 pg/ml; P < 0.001) comparing donor negativity for HCV. PEG-IFN alpha-2a treatment induces a marked decline in IL-18 and remission of hepatic inflammatory in responders at week 24 and week 48 follow-up time point, while increased levels persist in those in whom the HCV infection was not eliminated by the therapy. We proposed declined IL-18 levels favor for virus solution, while persistent raised IL-18 associated with PEG-IFN treatment failure.

Methylation status of the interferon-gamma gene promoter in chronic hepatitis B / 药物分析学报

Objective To evaluate the methylation status at CpG site -55 in the interferon-gamma (IFN-7) gene promoter and its effect on IFN-7 expression in chronic hepatitis B. Method The authors recruited 30 patients with UBeAg-positive chronic hepatitis B (CHB), 30 HBeAg-negative CHB patients, and 30 healthy blood donors. Pyrosequeneing was used to determine the methylation status at CpG site -55 in the IFN-γ gene promoter following bisulfite treatment of DNA in peripheral blood mononuclear cells (PBMCs). The expression of IFN-γ was analyzed by real-time RT-PCR and ELISA. HBV DNA in PBMCs was detected by nested PCR. Results The methylation level at CpG site -55 in the IFN-γ gene promoter was significantly increased, resulting in subsequent down-regulation of the expression of this cytoldne in CHB. The methylation level at CpG site -55 was significantly higher in HBeAg-positive patients than in HBeAg-negative ones (P<0.01) and was also significantly higher in PBMCs from HBV DNA-positive patients than from HBV DNA-negative ones (P<0.01) ; the methylation level at CpG site -55 was positively correlated with the amount of HBV DNA in serum (P<0.01). Oonclusion IFN-γ gene expression appears to be regulated by methylation of the IFN-γ gene promoter in CHB; the methylation level at CpG site -55 is associated with HBV infection.