抗HCV药物筛选模型的研究进展

丙型肝炎病毒(HepatitisCVirus,HCV)是丙型肝炎的致病体,至今治疗方式仅局限于采用IFN-α和利巴韦林等抗病毒途径。构建合适的抗HCV药物筛选模型,对HCV药物的研发具有重要的意义。近年来抗HCV药物筛选模型的研究,主要集中在针对特异性靶点的细胞模型、复制子系统以及全基因体外细胞培养系统方面。本文主要介绍这三方面的研究进展。     

2003年大连市部分血液透析者肝炎及相关病毒感染现况调查

[目的]了解血液透析患者肝炎及相关病毒感染状况，为采取防治对策提供依据。[方法]2003年，对在大连市部分医疗单位血液透析中心治疗的223例血液透析者进行HBsAg、抗-HBs、抗-HBc、HBeAg、抗-HBe、抗-HCV、抗-HGV、抗-TTV检测。[结果]检测223人，HBsAg、抗-HBs、抗-HBc、HBeAg、抗-HBe阳性率分别为10．8％、40，8％、71，3％、6．3％、24．2％，HBV感染率为78．0％；抗-HCV、抗-HGV、抗-TTV阳性率分别为35．0％、4．9％、33．6％。223人中，感染1种病毒的113人，占50．67％；感染2种或2种以上病毒的84人，占37．67％。[结论]血液透析是HBV、HCV、HGV、TTV感染的重要途径。     

1994～2004年泰安市城区饮食服务业从业人员查体资料分析

[目的]了解饮食服务业从业人员病毒性肝炎、伤寒、痢疾、肺结核及皮肤病（“五病”）感染状况，进一步加强对饮食服务业从业人员的健康管理。[方法]对泰安市城区直接管辖的饮食服务业从业人员1994～2004年查体资料进行分析。[结果]1994～2004年合计检查183532人，“五病”检出率为3．15％，呈逐年下降趋势；HBsAg阳性率为2．18％，伤寒检出率为0．27／万，细菌性痢疾检出率为0．03％，肺结核患病率为0．07％，皮肤病（手癣、指甲癣、手部湿疹、银屑或鳞屑病、化脓性皮肤病、渗出性皮肤病）患病率为0．87％。[结论]“五病”检出率呈逐年下降趋势，但乙肝病毒感染率仍然较高。     

北京市1997-2003年丙型肝炎疫情报告病例的流行病学分析

目的 了解北京市丙型肝炎流行趋势.方法 整理分析历年来传染病疫情报告中病毒性肝炎的资料.结果 北京市急性丙型肝炎报告年平均发病率为1/10万左右.1997-2003年病毒性肝炎总发病数逐年呈明显下降趋势,而急性丙肝逐年发病水平有所上升,急性丙肝报告病例数占病毒性肝炎发病总报告数的百分比亦呈上升趋势.急性丙肝主要发病集中在60岁以上的老年男性.结论 目前本市丙肝急性发病处于较低水平,应注重阻断静脉吸毒、性传播、医源性等途径的丙肝病毒传播.     

病毒感染对慢性阻塞性肺疾病患者气道炎症的作用

目的探讨病毒感染与慢性阻塞性肺疾病(COPD)的关系及其对气道炎症的作用. 方法收集COPD急性加重期患者84例及23例健康人血清,应用ELISA方法检测患者呼吸道合胞病毒(RSV)、单纯疱疹病毒Ⅰ型(HSV-1)、副流感病毒(PIV)、巨细胞病毒(CMV)、腺病毒(ADV)的特异性IgM、IgG抗体;根据病毒检测结果及临床表现分成2组:病毒感染组(A组)及细菌感染组(B组);用ELISA法检测A、B两组患者治疗前后诱导痰液中白介素8(IL-8)和肿瘤坏死因子α(TNF-α)的水平. 结果 84例COPD急性加重患者81例检测到病毒抗体,IgM阳性者28例(33.3%),其中RSVIgM比例最高(53.5%),其次为PIV(26.7%);IgM阳性与感冒样症状、无脓痰等有关;经治疗后A、B两组痰液IL-8和TNF-α水平显著降低(P<0.05),A组治疗后IL-8下降更明显(P<0.05),TNF-α水平的变化两组间差异无显著性. 结论病毒感染是COPD急性加重的重要因素,并且可引起气道炎症加重.     

A Point Mutation at F1737 of the Human Nav1.7 Sodium Channel Decreases Inhibition by Local Anesthetics

Abstract: Voltage-gated sodium channels (VGSC) contribute to the initiation and propagation of action potentials within the nervous system. These channels are important targets for inhibition by several classes of drugs, including antiarrhythmics and local anesthetics. Structural and pharmacological studies have localized the binding of these drugs to a common site near the channel's intracellular pore region. Point mutations within this region disrupt local anesthetic inhibition of cardiac, CNS, and skeletal muscle VGSC subtypes. This study was designed to test whether a similar structural requirement for drug binding exists on the peripheral neuronal VGSC subtype; Na_v1.7. In support of this hypothesis, an alanine substitution for phenylalanine at position 1737 (F1737A) in the pore lining S6 segment of domain IV in human Na_v1.7 reduced both use- and state- dependent inhibition of the local anesthetics, lidocaine and tetracaine, by 8–21-fold. We also saw a 2–3-fold reduction in tonic inhibition with the F1737A mutant. The voltage dependence of both activation and inactivation were unaffected by the F1737A mutation, however, fast inactivation kinetics were impaired, such that a significant portion of inward current remained at the end of a 20-ms depolarization. These data suggest that F1737 forms a part of the high affinity binding of local anesthetics as well as mediating inactivation processes of neuronal Na_v1.7 channels.     

PURIFICATION OF MS2 BACTERIOPHAGE FROM COMPLEX GROWTH MEDIA AND RESULTING ANALYSIS BY THE INTEGRATED VIRUS DETECTION SYSTEM (IVDS)

Purification and concentration of viruses from the background material is required whatever subsequent analysis methods are used. For the analysis of viruses it is essential and detection methods depend on this solution. This report demonstrates a methodology for theremoval of growth media from a virus preparation. A sample of MS2 was purified using a new ultrafiltration (UF) technique with hollow fibers. A typical MS2 virus sample with a nominal stated concentration of 1.4 × 10 12 plaque-forming units (pfu)/mL in the original growth media was used to demonstrate this method. After UF, the growth media was removed and thevirus counted using theintegrated virus detection system (IVDS)instrument. This report further describes the use of this ultrafiltration procedure to remove other impurities, such as cesium chloride and albumin, from solutions containing a purified solution of MS2 bacteriophage. These solutions were also analyzed using the IVDS instrument.     

Alcohol retail sales licenses and sexually transmitted infections in Texas counties, 2008-2015

Background: Research suggests that reduced retail alcohol outlet density may be associated with lower prevalence of HIV and other sexually transmitted infections (STIs). On-premise sale of alcohol for immediate consumption is theorized as increasing social interactions that can lead to sexual encounters. Objective: We examined associations between on- and off-premise retail alcohol sales licenses and number of newly diagnosed HIV and STI cases in Texas counties. Methods: Retail alcohol sales license data were obtained from the Texas Alcoholic Beverage Commission. HIV and bacterial STI data were obtained from the Texas Department of State Health Services. Associations between retail alcohol sales licenses and STIs were estimated using spatial linear models and Poisson mixed effects models for over-dispersed count data. Results: Adjusting for county-specific confounders, there was no evidence of residual spatial correlation. In Poisson models, each additional on-premise (e.g., bar and restaurant) alcohol license per 10,000 population in a county was associated with a 1.5% increase (95% CI: 0.4%, 2.6%) in the rate of HIV and a 2.4% increase (95% CI: 1.9%, 3.0%) in the rate of bacterial STIs, adjusting for potential confounders. In contrast, number of off-premise licenses (e.g., take-out stores) was inversely associated with the incidence of STI and HIV, although the association with HIV was not statistically significant. Conclusions: This study adds to the limited literature on the association between retail alcohol availability and STIs. Additional research is needed on the role of alcohol availability (and policies affecting availability) in the spread of HIV and other STIs.     

Tumour‐associated mast cells in classical Hodgkin's lymphoma: correlation with histological subtype,other tumour‐infiltrating inflammatory cell subsets and outcome

The tumour microenvironment in classical Hodgkin's lymphoma (cHL) is characterised by a minor population of neoplastic Hodgkin and Reed–Sternberg cells within a heterogeneous background of non‐neoplastic bystanders cells, including mast cells. The number of infiltrating mast cells in cHL has been reported to correlate with poor prognosis. We used immunohistochemistry to assess the degree of tumour‐infiltrating mast cells in cHL tissue microarrays and correlated this with clinico‐pathological features and prognosis in a cohort of homogeneously treated patients with Hodgkin's disease. A high degree of tumour mast cells was associated with nodular sclerosis (NS) subtype histology (P = 0.0002). Moreover, the number of mast cells was inversely correlated with the numbers of CD68+ and CD163+ macrophages (P = 0.0001 and P = 0.003, respectively) and with the number of granzyme+ cytotoxic cells (P = 0.004). The degree of mast cell infiltration was not a prognostic factor in cHL of nodular sclerosis subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast cells correlated with significantly poorer outcome both in terms of overall (P = 0.03) and event‐free survival (P = 0.01). Further studies are warranted into the biological mechanisms underlying this adverse outcome and their possible therapeutic implications.