Matrine is an effective natural product isolated from the traditional herb,Sophora flavescens,with wide range of pharmacological and clinical effects and treating as the treatment for chronic viral hepatitis in clinic.Currently,the mainstream clinical preparations of matrine involved injections,tablets,capsules and suppositories,while preparations under development included targeting preparations,sustained-release preparations and transdermal drug delivery preparations.Admittedly,It can significantly improve the biological utilization of matrine through the optimization of its clinical preparations for with scientific researches and the development of new dosage forms.While the clinical applications will be expanded and the clinical efficacy of the preparations of matrine enhanced with the development of researches for new dosage forms and drugs and the application of new materials.It may be also benefical to the study of monomer compositions of Chinese material medica,including the development of the preparation of matrine.Rested on the recent studies,pharmacological activities,preparation methods and researches for the preparations of matrine was summarized in this text for providing a reference for developing its preparations in the future.

Objective To evaluate the efficacy of pegylated interferon ( PegIFN ) α-2a plus ribavirin ( RBV) therapy for chronic hepatitis C ( CHC) in non-responders, and to investigate the related influencing factors.Methods A prospective, open, multicenter and randomized study was conducted.A total of 81 CHC non-responders were recruited from 10 clinical centers during February 2009 to November 2011.Patients were randomly assigned into two groups:group A (n=37) was given PegIFNα-2a plus RBV treatment for 72 weeks and group B (n=44) was given PegIFNα-2a plus RBV treatment for 96 weeks.Both groups were followed up for 24 weeks after treatment.Virological responses in two groups were observed, and treatment efficacies among patients with different genotypes, and among those with different previous treatment were compared.SAS software was used for statistical analysis.Results Fifty-two patients ( 28 from group A and 24 from group B) completed the study in total.The rates of rapid virological response ( RVR) , complete early virological response ( cEVR ) , end of treatment viral response ( ETVR ) and sustained virological response (SVR) in group A were 25.0% (7/28), 60.7% (17/28), 67.9%(19/28) and 60.7%(17/28), respectively; while those in the group B were 41.7% (10/24), 70.8%(17/24), 70.8%(17/24) and 70.8% (17/24), respectively; and there were no significant differences between two groups (P>0.05).SVR was observed in 82.9%(29/35) of patients with CC genotype of IL-28B, which was higher than that in patients with other genotypes ( 3/13 ) , and the difference was of statistical significance (P<0.01).There was no significant difference in viral responses between patients previously treated with IFN plus RBV and those treated by IFN only (P>0.05).The rates of RVR, cEVR, ETVR and SVR in patients who were previously treated with IFN were 36.4%(12/33), 81.8%(27/33), 81.8%(27/33) and 75.8%(25/33), and the rates of cEVR, ETVR and SVR were higher than those in patients who were previously treated with PegIFN (P<0.05), but no significant difference was observed in RVR (P>0.05).Adverse events occurred in 38 patients (46.9%), but no severe ones were observed. Conclusion The efficacy of PegIFNα-2a plus RBV therapy for CHC in non-responders is satisfactory, which may influenced by IL-28B genotypes and previous treatment.

Hepacivirus ; Hepatitis C ; therapy ; Humans

Objective:To explore whether hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) preconditioning can relieve inflammation, reduce cell apoptosis and alleviate renal ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomly divided into three groups of sham operation (sham), ischemia reperfusion injury (IRI) and IRI+ HIF-PHI ( n=6 each). In IRI+ HIF-PHI group, mice received an intragastric dose of roxadustat (20 mg/kg) every other day one week before. After renal IRI modeling, serum creatinine (SCr) level was monitored and hematoxylin-eosin (HE) staining employed for observing the pathological changes of renal tissue and scoring injury degree. Apoptosis of renal tubular epithelial cells was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mRNA expressions of HIF-1α, TNF-α and IL-1β in renal tissues. Immunofluorescence and immunohistochemistry were employed for detecting the expressions of hypoxia-inducing factor 1α (HIF-1α), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Results:As compared with IRI group, SCr level declined markedly in IRI+ HIF-PHI group ( P<0.01), renal tissue injury improved markedly, semi-quantitative score of renal tubule injury dropped ( P<0.01), apoptotic cells decreased ( P<0.01) and the expression levels of TNF-α and IL-1β declined ( P<0.05). Compared with sham group, the mRNA expression of HIF-1α was not significantly elevated in IRI group ( P>0.05). Immunofluorescence showed that the expression of HIF-1α in medulla of renal tissues was up-regulated in IRI group, but not markedly in cortex. While the mRNA expression of HIF-1α was markedly up-regulated after a pretreatment of HIF-PHI ( P<0.05), the expression spiked markedly in renal cortex, but was weaker in medulla than that in IRI group. Conclusions:HIF-PHI can boost the expression level of HIF-1α, reduce the expression of inflammatory factors, relieve the inflammatory response, reduce cell apoptosis, improve renal function and alleviate renal ischemia reperfusion injury.

OBJECTIVETo perform a prospective,multicenter,open,randomized study to determine a treatment regimen for treatment-naive patients with refractory chronic hepatitis C (RHC) using the predictive value (PV) of early virological response (EVR).

METHODSA total of 438 patients from 18 hospitals were recruited between December 2008 and December 2010 and administered peg-interferon/ribavirin treatment for 12 weeks. Patients who achieved complete EVR (cEVR) were assigned to group A for a 48-week course of treatment, while patients without cEVR were randomly allocated to either group B 1 for a 72-week course of treatment or to group B2 for a 96-week course of treatment. Serum hepatitis C virus RNA levels at baseline,treatment weeks 4, 12 and 24, end of treatment, and post-treatment week 24 were measured and used to evaluate the efficiency of therapy.

RESULTSThe overall sustained virological response (SVR) rate was 85.1%. In all, 91.0% of patients achieved cEVR and were assigned to group A, which had an SVR rate of 90.8%. There was no statistically significant difference in the SVR rates of groups B1 and B2 (29.4% vs. 25.0%, P more than 0.05). The positive PV of rapid virological response (RVR), cEVR and delayed virological response (DVR) for SVR was 93.4%, 90.8% and 77.8% respectively, and the negative PV of RVR, EVR and DVR for SVR was 28.0%, 93.3% and 100% respectively. Overall, 66.9% of the patients experienced adverse events (AEs), but only 1.9% of patients experienced sevcre AEs.

CONCLUSIONThe majority of Chinese RHC treatmentna(i)ve patients (91.0%) can achieve cEVR and a high SVR rate with a low rate of severe AEs using the cEVR guided personal treatment regimen.

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.