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

Objective To investigate the relationship between the mechanism of gynecomastia and serum hormone levels ,as well as liver function in male patients with liver cirrhosis .Methods Forty‐six male patients with liver cirrhosis and gynecomastia were collected as gynecomastia group from March 2013 to March 2014 ,and at the same period seventy male patients with liver cirrhosis but without gynecomastia were studied as non‐gynecomastia group . The condition of mammogenesis and maximum of breast thickness were measured by bilateral breast ultrasound .Hormones including luteinizing hormone (LH) ,follicle‐stimulating hormone (FSH) , prolactin (PRL) ,estradiol (E2) ,progesterone (PRGE) ,and testosterone (T);liver function including alanine aminotransferase (ALT) ,aspartate aminotransferase (AST) ,total bilirubin (TBil) and serum albumin (Alb);blood coagulation function including prothrombin time (PT) ,platelet count (PLT) were examined and the Child‐Pugh scores were calculated .t‐test was performed for results comparison between gynecomastia group and non‐gynecomastia groups .Chi‐square test was used to compare the difference in drinking rate between two groups . The patients of gynecomastia group and non‐gynecomastia group were further divided into Child‐Pugh Grade A ,B and C subgroups according to Child‐Pugh scores and the patients of gynecomastia group were divided into subgroups according etiology such as posthepatitic cirrhosis ,alcoholic liver cirrhosis and posthepatitic cirrhosis combined with alcoholc cirrhosis .Single factor analysis of variance was applied to compare the laboratory findings between subgroups ,and least‐significant difference mothod was used to further compared the differences between two subgroups .Results Among forty‐six male patients with liver cirrhosis and gynecomastia ,the mean thickness of breast was (7 .56 ± 2 .84) mm .All the differences of TBil ,Alb ,PT and Child‐Pugh score of Child‐Pugh grade patient were statistically significant between gynecomastia group and no gynecomastia group ((96 .72 ± 75 .86)μmol /L vs (60 .57 ± 54 .00)μmol /L ,(29 .12 ± 4 .90) g/L vs (33 .86 ± 6 .86) g/L ,(19 .06 ± 4 .76) s vs (15 .54 ± 2 .57) s ,11 .54 ± 0 .91 vs 10 .33 ± 0 .57 ,respectively ,t=2 .79 ,-4 .33 ,4 .58 ,2 .22 ,all P<0 .05) . The alcoholic drinking rate of gynecomastia group (74% (34/46) vs 53% (37/70)) increased ,and the difference was statistically significant compared with that of non‐gynecomastia group (χ2 =5 .183 , P<0 .05) .There was no statistically significant difference in E2 levels between gynecomastia group and non‐gynecomastia group (P>0 .05) .PRL and E2/T ratio ((404 .49 ± 297 .26) mU/L and 68 .74 ± 46 .37) were higher than those of non‐gynecomastia group ((279 .77 ± 111 .57) mU/L and 13 .60 ± 11 .55) ,and T was lower than that of non‐gynecomastia group ((7 .15 ± 5 .74) nmol/L vs (15 .46 ± 8 .53) nmol/L) ,and the differences were statistically significant (t=2 .72 ,7 .90、-6 .27;all P<0 .05) .Among patients with gynecomastia ,breast of patients with alcoholic liver cirrhosis was significantly thicker than that of patients with posthepatitic liver cirrhosis ((9 .25 ± 3 .59) mm vs (6 .67 ± 2 .48) mm) ,while the level of PRGE was lower than that of patients with posthepatitic liver cirrhosis ((0 .61 ± 0 .51 ) nmol/L vs (1 .49 ± 1 .47 ) nmol/L ) , and the differences were statistically significant (F= 3 .634 and 2 .674 ,both P< 0 .05) .Along with the severity of liver injury ,E2 level of gynecomastia group gradually increased ,however there was non‐statistically significant difference compared with non‐gynecomastia group (P>0 .05) .T level of gynecomastia group gradually decreased ,and those of Child‐Pugh B ,C subgroup ((8 .20 ± 7 .58) nmol/L and (4 .18 ± 3 .76) nmol/L) were siginificantly lower than that of Child‐Pugh A subgroup of non‐gynecomastia group ((17 .64 ± 9 .04) nmol/L ,F=9 .37 ,P<0 .05) .The E2/T levels of gynecomastic group gradually increased .There was significant difference in E2/T level between Child‐Pugh C subgroup of gynecomastia group (105 .49 ± 94 .42) and Child‐Pugh A grade subgroup of non‐gynecomastia group (11 .38 ± 9 .60 ,F=12 .57 ,P<0 .05) .Conclusions There are different degrees of sex hormone disorder in the serum of male patients with liver cirrhosis and gynecomastia which is more significant in PRL ,T and E2/T .T and E2/T level are correlated with the degree of liver functional impairment .Gynecomastia in alcoholic liver cirrhosis is more severe than that of posthepatitic liver cirrhosis .

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.

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.

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.

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 consistency of hemoglobin (Hb) as an diagnostic index for iron deficiency anemia (IDA) in pregnant women with serum ferritin (SF) and free erythrocyte protoporphyrin (FEP).Methods Hb,SF and FEP were assayed for 506 pregnant women with various gestational weeks for the diagnosis of IDA with Hb

0.05). ConclusionsTwo methods of fibero tomy do not effect on the periodontal tissues. The PSP is more excellent than t he MSF in preventing the corrected teeth from relapsing and keeping the aest hetic feeling of the gingival shape.

Aim To investigate the expression of phosphorylated JNK1/JNK2 and the protection of 11,12-EET in ischemic and reperfusion rat heart.Method The expression of JNK1/JNK2 was detected with western blot method and the changing of heart function during ischemia/reperfusion process was observed in different groups. Results The cardiac function (+dp/dt_(max)%,-dp/dt_(max)% and LVDP)of reperfusion periods(30 min) apparently decreased in ischemia/reperfusion (I/R) group contrasted with Sham group, short ischemia(SI)+I/R group and EET+I/R group,and the expression of phosphorylated JNK1/JNK2 increased in I/R group contrasted with nromal group,Sham group and EET+I/R group.Conclusion The myocardial protection of 11,12-EET ( 6.24?10~(-8) mol?L~(-1)) is able to inhibit the expression of phosphorylated JNK1/JNK2.

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.