基于中药特点的肝毒性分析在疾病临床管理与安全性系统评价中的作用

目的:研究基于中药特点的肝毒性分析在疾病临床管理与安全性系统评价中的作用。方法:选择医院内分泌风湿科2021年5月—2023年8月收治的150例患者为研究对象,分为对照组和观察组,每组75例。对照组采用常规疾病临床管理,观察组基于中药特点的肝毒性分析进行疾病临床管理,比较两组患者管理前后的中成药临床应用管理质量、疾病临床管理质量、肝毒性反应情况。结果:管理前,两组患者中成药临床应用管理质量、疾病临床管理质量各项评价指标评分及肝毒性反应各项检测指标结果差异均无统计学意义(P>0.05)。管理后两组患者中成药临床应用管理质量产生明显差异,观察组患者中成药毒性分析、中成药毒性辨识、中成药毒性预防、中成药毒性处理方面的评分均明显较对照组高(P<0.05);管理后两组患者疾病临床管理质量产生明显差异,观察组患者肿胀消退、疼痛缓解、舌质改善、活动恢复方面的评分均明显较对照组高(P<0.05);管理后两组患者肝毒性反应各项检测指标结果产生明显差异,观察组患者ALT、AST、ALP方面的检测值均明显较对照组低(P<0.05)。结论:采取基于中药特点的肝毒性分析进行疾病临床管理不仅可以为中成药临床应用管理质量及疾病临床管理质量带来更为有力的保障,而且还有利于帮助患者降低中成药用药过程中对其造成的肝毒性反应,有利于保护患者肝功能,提高用药安全性。

Aptamers Against Viral Hepatitis:from Rational Design to Practical Application

Aptamers are short nucleic acids or peptides that strongly bind to a protein of interest and functionally inhibit a given target protein at the intracellular level. Besides high affinity and specificity, aptamers have several advantages over traditional antibodies. Hence, they have been broadly selected to develop antiviral agents for therapeutic applications against hepatitis B and C viruses (HBV, HCV). This review provides a summary of in vitro selection and characterization of aptamers against viral hepatitis, which is of practical significance in drug discovery.

Silencing of UBP43 by shRNA Enhances the Antiviral Activity of Interferon against Hepatitis B Virus

Previous studies have shown that expression of the interferon-sensitive gene （ISG）15 protease UBP43 is increased in the liver biopsy specimens of patients who do not respond to interferon （IFN）-α therapy. We hypothesized that UBP43 might hinder the ability of IFN to inhibit HBV replication. In this study, we investigated whether vector-based siRNA promoted by HI （psiUBP43） could enhance IFN inhibiting HBV replication in cell culture. UBP43 was specifically silenced using shRNA. In HepG2.2.15 cells, the HBeAg and HBV DNA levels were significantly reduced by IFN after transfection of shRNA, imphicated that vector-based siRNA promoted by H1 （psiUBP43） could enhance IFN inhibiting HBV replication in cell culture. These data suggest that UBP43 modulates the anti-HBV type I IFN response, and is a possible therapeutic target for the treatment of HBV infection.

Expression and Identification of Inclusion Forming-related Domain of NS80 Nonstructural Protein of Grass Carp Reovirus

Grass carp reovirus （GCRV）, a double stranded RNA virus that infects aquatic animals, often with disastrous effects, belongs to the genus Aquareovirus and family Reoviridea. Similar to other reoviruses, genome replication of GCRV in infected cells occurs in cytoplasmic inclusion bodies, also called viral factories. Sequences analysis revealed the nonstmctural protein NS80, encoded by GCRV segment 4, has a high similarity with μNS in MRV（Mammalian orthoreovimses）, which may be associated with viral factory formation. To understand the function of the μNS80 protein in virus replication, the initial expression and identification of the immunogenicity of the GCRV NS80 protein inclusion forming-related region （335-742） was investigated in this study. It is shown that the over-expressed fusion protein was produced by inducing with IPTG at 28℃. In addition, serum specific rabbit antibody was obtained by using super purified recombinant NS80（335-742） protein as antigen. Moreover, the expressed protein was able to bind to anti-his-tag monoclonal antibody （mouse） and NS80〈335.742） specific rabbit antibody. Further western blot analysis indicates that the antiserum could detect NS80 or NS80C protein expression in GCRV infected cells. This data provides a foundation for further investigation of the role of NS80 in viral inclusion formation and virion assembly.

Association of chronic viral hepatitis B with insulin resistance

AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean adults.METHODS:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this study.Subjects diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were rejected.Anthropometry,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all subjects.Homeostasis model assessment(HOMA),quantitative insulin check index(QUICKI),and Mf fm index were used for determining insulin sensitivity.Each participant was categorized into a negative,recovery,or CVHB group.To compare variables between groups,a t-test and/or one-way analysis of variance were used.Partial correlation coefficients were computed to present the association between insulin resistance and other variables.Multiple logistic regression analysis was used to assess the independent association between CVHB and IR.RESULTS:The mean age of men and women were 48.9 and 48.6 years,respectively.Subjects in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P = 0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P < 0.001 in women)],cystatin C [(0.96 ± 0.15 mg/dL vs 1.02 ± 0.22 mg/dL,P < 0.001 in men),(0.84 ± 0.15 mg/dL vs 0.90 ± 0.16 mg/dL,P < 0.001 in women)],fasting insulin [(5.47 ± 3.38 U/mL vs 6.12 ± 4.62 U/mL,P < 0.001 in men),(4.57 ± 2.82 U/mL vs 5.06 ± 3.10 U/mL,P < 0.001 in women)] and HOMA index [(1.24 ± 0.86 vs 1.43 ± 1.24,P < 0.001 in men),(1.02 ± 0.76 vs 1.13 ± 0.87,P = 0.033 in women)] compared to control group.The HOMA index revealed a positive correlation with body mass index(BMI)(r = 0.378,P < 0.001),waist circumference(r =0.356,P < 0.001),percent body fat(r = 0.296,P < 0.001),systolic blood pressure(r = 0.202,P < 0.001),total cholesterol(r = 0.134,P < 0.001),triglycerides(r = 0.292,P < 0.001),cystatin C(r = 0.069,P < 0.001) and uric acid(r = 0.142,P < 0.001).The QUICKI index revealed a negative correlation with BMI(r =-0.254,P < 0.001),waist circumference(r = 0-0.243,P < 0.001),percent body fat(r =-0.217,P < 0.001),systolic blood pressure(r =-0.132,P < 0.001),total cholesterol(r =-0.106,P < 0.001),triglycerides(r =-0.205,P < 0.001),cystatin C(r =-0.044,P < 0.001) and uric acid(r =-0.096,P < 0.001).For subjects identified with IR,the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534(95% CI:1.158-2.031,HOMA index criteria) or 1.566(95% CI:1.124-2.182,QUICKI criteria) after adjustment for age,gender,BMI,and amount of alcohol consumption.CONCLUSION:Our study demonstrates that CVHB is associated with IR.CVHB may need to be monitored for occurrence of IR and diabetes mellitus.

Performance verification and comparison of TianLong automatic hypersensitive hepatitis B virus DNA quantification system with Roche CAP/CTM system

AIM To investigate and compare the analytical and clinical performance of Tian Long automatic hypersensitive hepatitis B virus(HBV) DNA quantification system and Roche CAP/CTM system.METHODS Two hundred blood samples for HBV DNA testing, HBV-DNA negative samples and high-titer HBV-DNA mixture samples were collected and prepared. National standard materials for serum HBV and a worldwide HBV DNA panel were employed for performance verification. The analytical performance, such as limit of detection, limit of quantification, accuracy, precision, reproducibility, linearity, genotype coverage and cross-contamination, was determined using the Tian Long automatic hypersensitive HBV DNA quantification system(TL system). Correlation and Bland-Altman plot analyses were carried out to compare the clinical performance of the TL system assay and the CAP/CTM system. RESULTS The detection limit of the TL system was 10 IU/m L, and its limit of quantification was 30 IU/m L. The differences between the expected and tested concentrations of the national standards were less than ± 0.4 Log10 IU/m L, which showed high accuracy of the system. Results of the precision, reproducibility and linearity tests showed that the multiple test coefficient of variation(CV) of the same sample was less than 5% for 102-106 IU/m L; and for 30-108 IU/m L, the linear correlation coefficient r2 = 0.99. The TL system detected HBV DNA(A-H) genotypes and there was no cross-contamination during the "checkerboard" test. When compared with the CAP/CTM assay, the two assays showed 100% consistency in both negative and positive sample results(15 negative samples and 185 positive samples). No statistical differences between the two assays in the HBV DNA quantification values were observed(P > 0.05). Correlation analysis indicated a significant correlation between the two assays, r2 = 0.9774. The Bland-Altman plot analysis showed that 98.9% of the positive data were within the 95% acceptable range, and the maximum difference was-0.49.CONCLUSION The TL system has good analytical performance, and exhibits good agreement with the CAP/CTM system in clinical performance.

SEQUENCE ANALYSIS OF THE NS5 REGION OF GBVC/HGV AND DETECTION OF THE VIRUS BY REVERSE TRANSCRIPTASE PCR

GBV C/HGV is a newly identified virus associated with human hepatitis In this study, the nucleotide sequences of the partial NS5 gene of GBV C/HGV derived from sera of 8 Chinese patients were determined The nucleotide homology among the 8 isolates were 92% on average On the basis of sequence analysis, two sets of oligonucleotide primers derived from highly conserved region of GBV C/HGV NS5 gene were designed to establish both sensitive and specific nested PCR for detection of GBV C/HGV RNA 253 Chinese patients were examined for the virus RNA GBV C/HGV RNA positive rates in patients infected with HBV, HCV and patients with chronic non B,non C hepatitis were 18 4%, 19 8% and 8 9% respectively This result suggested that HBV,HCV and GBV C/HGV shared the same transmission risk factors 8 patients with GBV C/HGV and HCV coinfection were retrospectively observed for the response to interferon Coinfection with GBV/HGV did not negatively influence the responsiveness of HCV, and GBV C/HGV was sensitive to interferon to a certain degree

Association between serum vitamin D and severity of liver fibrosis in chronic hepatitis C patients: a systematic meta-analysis

To conduct a systematic review of group studies assessing the association of serum vitamin D status with the severity of liver fibrosis in chronic hepatitis C patients using meta-analysis. The relevant research literatures were identified by searching PubMed and EMBASE databases prior to October 2013 with no restrictions. We included group studies that reported odds ratio（OR） estimates with 95% confidence intervals（CIs） or a mean with standard deviation（SD） for the association between serum vitamin D status and the severity of liver fibrosis in chronic hepatitis C patients. Approximately 8321 participants from several countries were included in this analysis. Six studies on serum vitamin D status and the severity of liver fibrosis were included in this meta-analysis. ORs with 95% CIs were extracted from four studies and the pooled ORs were 0.866（95% CI, 0.649 to 1.157）. The means with SDs were extracted from three studies and the pooled means were-0.487（95% CI,-0.659 to-0.315）. There was statistically significant heterogeneity among the mean data extracted studies（P=0.029; I^2=71.8%） but not among the OR data extracted studies（P=0.061; I^2=55.6%）. Finally, results from the mean data extracted studies suggest that lower serum vitamin D is a risk factor for the severity of liver fibrosis in chronic hepatitis C patients. However, there is no conclusive evidence on this association because of inconsistencies between the OR data extracted studies and the mean data extracted studies.

Global dynamics of hepatitis C viral infection with logistic proliferation

A modified mathematical model of hepatitis C viral dynamics has been presented in this paper, which is described by four coupled ordinary differential equations. The aim of this paper is to perform global stability analysis using geometric approach to stability, based on the higher-order generalization of Bendixson＇s criterion. The result is also supported numerically. An important epidemiological issue of eradicating hepatitis C virus has been addressed through the global stability analysis.