Objective:To analyze the actuality and explore new teaching methods for clerkship of infectious disease.Methods:The students were divided into group A and group B.The latter group received the traditional teaching method;for the former group,on the basis of analysis of current teaching situation,we put forward a set of new teaching methods,including a test every morning before their class,reviewing the theory during class,discussing typical cases and asking some questions before the end of class.Results The scores in comprehension and application part in examination of group A were higher than those of group B(P

Background and aims:To investigate the safety and efficacy of direct-acting antiviral(DAA)regimens in a cohort of Chinese patients with chronic hepatitis C virus(HCV)infection. Methods:A total of 222 adult Chinese patients were enrolled and treated via DAA regimens in accor-dance with HCV management guidelines.Treatment responses were evaluated 4 weeks after treatment,at the end of treatment(EOT)and 12 weeks post-treatment.Virological responses,biochemical re-sponses,model for end-stage liver disease(MELD)and Child-Pugh(CP)scores were recorded. Results:A total of 218 patients(98.2％)achieved sustained virological response 12 weeks post-treatment and 4 patients relapsed.The combined number of rapid virological responses for all six regimens was 170/222(76.6％),and 221/222(99.6％)had achieved virological responses by the end of treatment.In decompensated cirrhosis patients the baseline mean CP score was 6.8±1.3 and the mean MELD score was 10.1±3.3.Compared with the mean CP score at baseline,the mean score is significantly lower at the end of treatment(5.7±1.3)and 12 weeks post-treatment(5.6±1.0).Estimated glomerular filtration rates did not differ significantly from baseline during the treatment or 12 weeks post-treatment.The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 42/172(24.4％),and in patients with decompensated cirrhosis it was 8/22(36.4％).The most frequently reported adverse events were elevated indirect bilirubin,fatigue and rash.There were no cases of serious adverse events,death or treatment discontinuation because of adverse events. Conclusion:DAA regimens were highly effective and well tolerated irrespective of HCV genotype,cirrhosis,liver or kidney transplantation,hepatocellular carcinoma,HCV/hepatitis B virus co-infection,or renal failure.

Objective: To investigate the effects of resolvin D1 on autophagy in the prevention of acute pancreatitis (AP) in mice. Methods: Thirty C57BL/6 mice were divided into control group, AP group and resolvin D1 group. AP model was established by intraperitoneal injection of cerulein at 50 μg·kg^-1·h^-1. Resolvin D1 was intraperitoneally given at 50 μg/kg one hour before and four hours after modeling. The mice of control group were intraperitoneally injected the same volume of 0.9% sodium chloride solution. The serum levels of amylase and lipase were measured by colorimetric method. The pathological injury of the lung and pancreatitis were observed under optical microscope. Autophagic vacuoles in acinar cells of pancreas of mice were evaluated by transmission electron microscope. And the expressions of autophagy related markers Beclin-1, p62 and LC3-Ⅱ at the mRNA and protein levels in pancreas of mice were detected by real time quantitative polymerase chain reaction (RT-qPCR) and Western blotting method. One-way analysis of variance and SNK-q were performed for statistical analysis. Results: There were statistically significant differences in serum amylase and lipase levels between control group, AP group and resolvin D1 group (F=62.99 and 149.69, both P<0.01). The serum amylase and lipase levels of mice in resolvin D1 group were lower than those of AP group ((525.08±41.12) U/L vs. (752.62±42.03) U/L, (758.24±134.77) U/L vs. (1 201.06±112.53) U/L), and the differences were both statistically significant (both SNK-q test and P<0.01). In addition, there were statistically significant differences in the ratio of the pancreas and lung wet mass to body mass between control group, AP group and resolvin D1 group (F=11.36 and 18.51, both P<0.05). Pathological injury scores of pancreas and lung of resolvin D1 group were both lower than those of AP group (3.3±0.6 vs. 5.6±0.6, 5.4±0.5 vs. 8.8±0.4), and the differences were statistically significant (both SNK-q test and P<0.05). The results of transmission electron microscopy observation revealed that the number of autophagic vacuole of resolvin D1 group was less than that of AP group, and the size was smaller. Moreover, there were statistically significant differences in Beclin-1, p62 and LC3-Ⅱ mRNA between control group, AP group and resolvin D1 group (F=270.95, 151.83 and 124.77, all P<0.05). The relative expression mRNA levels of Beclin-1, p62 and LC3-Ⅱ of resolvin D1 group were 1.59±0.12, 2.75±0.27 and 1.34±0.14, respectively, which were lower than those of AP group (2.68±0.13, 3.32±0.30 and 3.37±0.26, respectively), and the differences were statistically significant (all SNK-q test and P<0.05). There were statistically significant differences in the expressions of Beclin-1, p62 and LC3-Ⅱat the protein level between control group, AP group and resolvin D1 group (F=116.63, 384.40 and 192.45, all P<0.05). The expressions of Beclin-1, p62 and LC3-Ⅱ at protein level of resolvin D1 group were 0.98±0.03, 0.57±0.04 and 0.31±0.03, respectively, which were lower than those of AP group (1.34±0.07, 1.02±0.03 and 0.48±0.04, respectively), and the differences were statistically significant (all SNK-q test and P<0.05). Conclusion Resolvin D1 ameliorates the severity of AP by attenuating the impaired autophagy and restoring autophagic flux in AP mice.

Objective: To evaluate the efficacy and safety of DCV-based DAAs therapy for chronic HCV infected Chinese patients. Methods: An open-label, non-randomized, prospective study was designed. Fifty-two patients with chronic HCV infection were enrolled. Among them, there was one patient after liver transplantation, 2 patients after kidney transplantation, 3 patients with hepatocellular carcinoma, and 4 patients with HBV infection. Thirteen cases with chronic hepatitis C (one compensated cirrhosis) who were negative for resistance-related variants [NS5A RAS (-)] of gene 1b and NS5A were treated with daclatasvir (DCV) + asunaprevir (ASV) for 24 weeks. Twenty-five cases of CHC (six compensated cirrhosis) with GT 1b, 2a, 3a, 3b, 6a were treated with DCV + SOF ± RBV for 24 weeks. 8 cases with decompensated cirrhosis of gene 1b and NS5A RAS(-) were given DCV + SOF + RBV regimen for 12 weeks. Six cases with decompensated cirrhosis, of gene 2a, 1b, 2a, 3a, 3b, were given DCV + SOF + RBV regimen for 24 weeks. HCV RNA, blood routine test, liver and kidney function, and upper abdominal ultrasound/MRI were measured at baseline, 4 weeks of treatment, end of treatment, and 12 weeks of follow-up. The incidence of adverse events and laboratory abnormalities during treatment were recorded. A t-test was used to compare the measurement data between two groups, and analysis of variance was used to compare the measurement data between multiple groups. Results: Sixteen patients (100%) achieved SVR12 after treatment, with 0% recurrence rate. Rapid virological response (RVR) of the four treatment regimens were 76.92%, 54.17%, 87.50%, and 83.33%, respectively, and 32 patients achieved 100% virological response after the completion of treatment. The incidence of adverse events of chronic hepatitis C with cirrhosis and decompensated cirrhosis was 62.5% and 64.29%, respectively. The most common adverse event was fatigue in CHC (25.00%), and elevated indirect bilirubin in decompensated cirrhosis (42.86%). No serious adverse drug events, deaths or adverse reactions occurred. Conclusion DCV-based DAAs regimen is promising option for the treatment of HCV genotypes, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and HCV infection after liver/kidney transplantation in china. Above all, it has high SVR12 with good tolerability and safety profile.

BACKGROUNDEndostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.

METHODSFour hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .

RESULTSOf 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .

CONCLUSIONSThe addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .