Hepatitis c virus (HCV) infection has become one of the global public health problem,while there is no vaccine to prevent HCV infection, the so-called "cocktail" therapy that use a combination of drugs targeting multiple steps in the HCV infection cycle could achieve better curative effect. the process of HCV entering into host cell is the important step of drug intervention, in which HCV envelope protein El and E2, Host cell factors including Heparan sulfate(HS), CD81, scavenger receptor class B type I (SR-BI), Occludin (OCLD), Claudin (CLDN), low densitity lipoprotein receptor (LDLR), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN), Liver/lymph node specific ICAM-3-grabbing integrin(L-SIGN), trans- ferrin receptor 1 (TfR1) and so on play a important role. The virus and the host factors can be used as targets of hcv entry inhibitors many studies have shown that as novel and promising compounds, HCV entry inhibitors combinating with other drugs can be more effective in the treatment of HCV, this paper have re- viewed targets and inhibitors of HCV enterring into host cell since 1990s.
Animals ; Antiviral Agents ; pharmacology ; Hepacivirus ; drug effects ; physiology ; Hepatitis C ; genetics ; metabolism ; virology ; Humans ; Receptors, Virus ; genetics ; metabolism ; Viral Envelope Proteins ; genetics ; metabolism ; Virus Internalization ; drug effects

Acute Disease ; Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Paraquat ; poisoning ; Retrospective Studies ; Young Adult

Objective To observe different effects of cyclic and continuous nutrition infusion on serum nutritional indicators, peripheral white blood cell counts (WBC), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) and acute physiology and chronic health evaluation Ⅲ (APACHE Ⅲ ) score in patients with mechanical ventilated respiratory failure (MVRF).Methods A cross-over and self-controlled trial was conducted in 48 patients with MVRF treated in a medical intensive care unit during December 2006 to June 2009, and continuous nutrition (group A) and cyclic nutrition (group B) were infused respectively for patients of the two groups.Serum levels of albumin (ALB), pre-albumin (PA), transferrin (TR), PaO2, PaCO2, WBC and APACHE Ⅲ score were measured for the patients with 24-hour continuous nutrition (group A) and 16-hour cyclic nutrition (group B)infusion.Effects of the two nutritional therapies were compared.Results After nutrition infusion, serum levels of ALB, PA and TR were (34±3)g/L, (196±28)mg/L and (2.1±0.3 ) g/L in group A, and (35 ±4) g/L, (198 ±25) mg/L and (2.0 ±0.4) g/L in group B, respectively; and PaO2 and PaCO2levels were (92 ± 12) mm Hg ( 1 mm Hg =0.133 kPa) and (42 ± 10) mm Hg in group A, and (91 ±9)mm Hg and (42 ± 10) mm Hg in group B, respectively.WBC and APACHE Ⅲ score were ( 11.8 ± 1.7) ×109/L and 38 ±7 in group A, and ( 12.6 ± 1.2) × 109/L and 40 ±6 in group B, respectively.Significant difference in serum levels of PA and TR was found between the two groups (PPA =0.019 and PTR =0.013),while there was no significant difference in other indictors between the two groups.Conclusions 24-hour continuous nutrition infusion for patients with MVRF can obviously improve their serum levels of PA and TR,but has no effect on serum level of ALB, PaO2, WBC and APACHE Ⅲ score in critical ill patients, as compared to those with 16-hour cyclic nutrition infusion.

Objective To evaluate the immunotoxicity effect of Liver targeting interferon (IFN -CSP) on mice.Methods Mice were randomly divided into five groups:low, middle and high dose of IFN-CSP, solvent control group(saline) and Positive control group (cyclophosphamide).They were injected subcutaneously for 2 weeks.Delayed hypersensitivity test was used to determine the cell immunefunction and plaque forming cell assay was used to determine the humoral immune function.Results There was no significant difference of the the index of immune organ and the ear swelling degree between IFN-CSP groups and control group.There was also no significant difference on hemolytic plaque test between them.Conclusion IFN-CSP has no significant effect on both cellular immunity function and humoral immune function of mice, this results will provides the basis for further safety evaluation.

AIM: In order to study the relationship between the ERK and p38 MAPK activation and the protection of 11, 12-epoxyeicosatrienoic acid (11, 12-EET) and ischemia preconditioning (IP), the effects of 11, 12-EET and ischemic preconditioning on phosphorylated ERK and p38 MAPK during ischemia and reperfusion in rat myocardium were examined. METHODS: The rat heart was subjected to ischemia for 5 min by ligating the left anterior descending coronary artery followed by reperfusion for 5 min (two times) to undergo ischemia preconditioning. The rats were divided into 5 groups: (1) control; (2) sham group; (3) ischemia/reperfusion (I/R) group, in which the rat heart suffered from 60 min ischemia followed by 30 min reperfusion; (4) IP plus I/R group; (5) EET plus I/R group, in which 6.28?10 -8 mol/L 11, 12-EET was injected intravenously 20 min before I/R. The heart function was examined, and phosphorylated ERK and p38 MAPK were detected by Western blot. RESULTS: At 30 min reperfusion, +dp/dt max ,-dp/dt max and LVDP decreased significantly in I/R group compared with sham group, IP plus I/R group and EET plus I/R group; Phosphorylated ERK1/2 level was higher in I/R group than sham group, but was lower in I/R group than IP plus I/R group and EET plus I/R group; Phosphorylated p38 MAPK level was lower in control, sham, IP plus I/R and EET plus I/R group than I/R group. CONCLUSION: 11,12-EET protects rat heart against ischemia/reperfusion injury, the mechanism may be related to activation of ERK1/2 and inhibition of p38 MAPK. [

Objective To measure the level of platelet derived growth factor-BB (PDGF-BB) in maintenance hemodialysis patients and investigate the significance of carotid atherosclerosis.Methods Thirty-six maintenance hemodialysis patients (test group) and 20 healthy controls (normal control group) were enrolled in this study.The level of PDGF-BB was measured by enzyme-linked immunosorbent assay in two groups.Intima-media thickness (IMT) and atherosclerotic plaques of the extracranial common carotid artery were measured by echocardiography.Results The level of IMT and the positive rate of carotid atherosclerosis in test group were significantly higher than those in normal control group [(1991.8 ± 228.6) μ mol/L vs.(71.2± 15.9) μmol/L,(36.78 ±3.40) g/Lvs.(41.96±2.07) g/L,(4.97 ±0.57) mmol/Lvs.(4.48 ±0.84) mmol/L][(1.01 ±0.23) mm vs.(0.72 ±0.15) mm,69.4％(25/36) vs.10.0％(2/20)](P＜ 0.01).The level of plasma creatinine,albumin and total cholesterol in test group were significantly higher than those in normal control group (P ＜ 0.01 or ＜ 0.05).The level of PDGF-BB in test group was significantly higher than that in normal control group[(93.27 ± 31.58) ng/L vs.(31.71 ± 15.78) ng/L,P ＜ 0.01].In test group,age and the level of PDGF-BB and triacylglycerol in carotid atherosclerosis patients were significantly higher than those in non-carotid atherosclerosis patients [(48.04 ± 9.97) years vs.(34.54 ± 10.35) years,(102.60 ± 32.87) ng/L vs.(72.06 ± 13.67) ng/L,(1.51 ± 0.59) mmol/L vs.(1.01 ± 0.27) mmol/L] (P ＜ 0.01).Regression analysis showed that age (β =0.346,P ＜ 0.01) and PDGF-BB (β =0.594,P＜ 0.01) were the important impacting factors for IMT.Conclusion The level of PDGF-BB is increased in maintenance hemodialysis patients,and it may play an important role in carotid atherosclerosis.

Ras/Raf/MEK/ERK singal transduction plays an important role in cell proliferation, differentiation, apoptosis, metastasis and metabolism. This investigation focused on this signal pathway and chose farnesyl transferase (FTase) as the main target and Raf-1 kinase as the second target. A lot of compounds were selected to construct the pharmacophore models of farnesyl transferase inhibitors (FTIs) and Raf-1 kinase inhibitors by using computer-aided drug design (CADD). The pharmacophore of FTIs is constituted by a hydrogen bonding acceptor, an aromatic ring, a positive ionizable and two hydrophobic regions; the pharmacophore of Raf-1 kinase is constituted by a hydrogen donor, a hydrogen acceptor, a hydrophobic regions and an aromatic ring. There are some similarities between the two pharmacophores. After analysis of the constructions of these two pharmacophores, some new aminomethylbenzoic acid derivatives with good forecasting activity against both of FTase and Raf-1 kinase were designed with these new pharmacophore models.

Objective To evaluate the clinical effects of AO clavicular hook plates in treatment of dislocation of acromioclavicular joint and/or fracture of distal clavicle in comparison with traditional means. Methods A retrospective analysis was done to compare the outcomes and complications between the treatment of dislocation of acromioclavicular joint and/or the fracture of distal clavicle by AO clavicular hook plates and the treatment by conventional devices (e.g. Kirschner’s wire, wire-cerclage, bolt, et al). Results 40 cases were followed up for 12 to 20 months and the average time was 14 months. According to Lazzcano’s criterion, the rate of excellent and fine of the clinical outcomes of the 2 groups was 100%and 78.6%respectively. After statistical Chi-square test, P=0.025. Therapeutic outcomes and complications of the former were obviously better than the latter. Conclusion Since AO clavicular hook plates display advantages of rigid fixation, non-invasion into articular surface, and possibility of early functional exercise in the treatment of acromioclavicular dislocation and fractures of distal clavicle, they are worthy of recommending.

Objective To observe the effect of Juli Sanjie Pill(JSP) on estrogen receptor(ER)? and ER? expression in the myometrium and hysteromyoma tissue,and to explore the correlation of ER? and ER? expression levels with the incidence of hysteromyoma. Methods Forty hysteromyoma patients were divided into two groups: 20 patients with operative indications after oral use of JSP and asking for operation,were enrolled in the treatment group,and other 20 patiens without mediation of medicine but asking for operation were in the control group.The ER? and ER? expression levels in hysteromyoma tissue and the surrounding normal myometrium of the two groups were detected by radioimmunoassay.Results There presented the expression of ER? and ER? in the hysteromyoma tissue and the surrounding normal myometrium of the two groups,and the levels in the hysteromyoma tissue were higher than that in the myometrium(P0.05).Conclusion The incidence of hysteromyoma is correlated with the local expression of ER? and ER? in the uterus.The therapeutic mechanism of JSP for hysteromyoma is probably related with the decrease of ER? and ER? expression levels in hysteromyoma tissue and with the decrease of ER? level in the surrounding normal myometrium.

By Analyzing the significance and objective,practicing the organizing and management of the clinical application teaching in department of gynecology,the author explored the new teaching methods in current social condition.