Gene delivery by lentivirus vectors

The capacity to efficiently transduce nondividing cells, shuttle large genetic payloads, and maintain stable long-term transgene expression are attributes that have brought lentiviral vectors to the forefront of gene delivery vehicles for research and therapeutic applications in a clinical setting. Our discussion initiates with advances in lentiviral vector development and how these sophisticated lentiviral vectors reflect improvements in safety, regarding the prevention of replication competent lentiviruses (RCLs), vector mobilization, and insertional mutagenesis. Additionally, we describe conventional molecular regulatory systems to manage gene expression levels in a spatial and temporal fashion in the context of a lentiviral vector. State of the art technology for lentiviral vector production by transient transfection and packaging cell lines are explicitly presented with current practices used for concentration, purification, titering, and determining the safety of a vector stock. We summarize lentiviral vector applications that have received a great deal of attention in recent years including the generation of transgenic animals and the stable delivery of RNA interference molecules. Concluding remarks address some of the successes in preclinical animals, and the recent transition of lentiviral vectors to human clinical trials as therapy for a variety of infectious and genetic diseases.     

感染耐亚胺培南鲍曼不动杆菌临床分布情况及耐药性分析

目的:探讨感染耐亚胺培南(IPM)鲍曼不动杆菌临床分布情况及耐药性。方法:回顾性分析2013~2015年榆林市中医院患者感染鲍曼不动杆菌的临床分布,并对耐亚胺培南鲍曼不动杆菌进行培养、鉴定及药敏试验,分析其耐药情况。结果:2013~2015年我院共分离培养出鲍曼不动杆菌185株,其中IPM耐药99株(53.51%),IPM敏感86株(46.49%)。绝大部分菌株分离自痰液标本(138株,74.59%),其次是血液标本(14株,7.57%)与尿液标本(12株,6.49%);来自ICU送检标本菌株数量最多(84株,45.41%),其次是呼吸内科标本(53株,28.65%)与神经内科标本(30株,16.22%)。不同标本类型及科室中IPM耐药及IPM敏感鲍曼不动杆菌占比无显著差异(P0.05)。IPM耐药鲍曼不动杆菌对抗菌药物耐药性均较高,其中以头孢哌酮/舒巴坦(CSL)敏感性最高(50.51%);IPM敏感鲍曼不动杆菌对部分抗菌药物耐药性尚可,其中以IPM敏感性最高(93.02%)。结论:耐亚胺培南鲍曼不动杆菌临床分布广泛,多重耐药性严重甚至出现泛耐药,应当对患者进行药敏试验,以药敏结果选择合适的抗菌药物进行使用。     

A registry for exposure and population health in the Altai region affected by fallout from the Semipalatinsk nuclear test site

A registry of the rural population in the Altai region exposed to fallout from nuclear tests at the Semipalatinsk test site (STS) was established more than four decades after the first Soviet nuclear explosion on August 29, 1949. Information about individuals living in an exposed and a control area was collected using all available local sources, such as kolkhoz documentation, school registries, medical treatment records and interviews with residents. As a result, a database comprising an exposed group of 39 179 individuals from 53 Altai region villages, 6769 external and 3303 internal controls was compiled. For several settlements, effective dose estimates reached the level of 1.5 Sv, while the average effective dose estimate in the exposed group was 340 mSv. Dosimetric data, vital status information and health records gathered at rayon and village medical facilities are held in the registry. Cause-of-death information for deceased residents is obtained from death registration forms archived at the Altai region vital statistics office. At present, a follow-up of approximately 40% of the population exposed in 1949 has been done. More will be added by searching for migrants to the larger towns of the Altai region, i.e. Barnaul, Rubtsovsk and Biisk. In order to assess the influence of radiation exposure, analytical studies with a case-control design for stomach and lung cancer are currently being prepared. The number of known cases is sufficient to detect an odds ratio of 1.5 at the 95% confidence level. Epidemiological studies in populations affected by fallout from STS may be equally important to the atomic bomb survivors’ study for the direct quantification of radiation effects. The range of exposure rates experienced will extend the acute high-dose-rate findings from Hiroshima/Nagasaki towards acute and protracted lower exposures, which are more relevant for radiation protection issues. Received: 3 March 1999 / Accepted in revised form: 8 June 1999     

22例糖尿病视神经病变综合治疗的疗效观察

目的：总结诊断及治疗糖尿病性视神经病变（diabeticopticneuropathy,DON）的临床经验,为本病的治疗和预防提供依据。方法：回顾性研究22例糖尿病视神经痛变的发病特点,在接受治疗的患者中严格控制血糖,应用复方樟柳碱注射液病侧颞浅动脉旁皮下注射,口服或静脉滴注活血化瘀药物,并口服维生素B1、维生素B2、肌苷片等营养视神经的药物,同时给予全身检查,包括对高血压、糖尿病等全身疾病的治疗,观察经综合治疗前后的视力、眼底、视野改变及眼底荧光血管造影（fundusfluoresceinall-giography,FFA）的特点等。结果：接受治疗的患者共有22例（29只眼）,治愈10例（12只眼）;好转7例（10只眼）,总有效率为79．3％。结论：糖尿病性视神经病变的及时正确诊断、系统的综合治疗,可有效提高视力,扩大视野。     

卵巢上皮癌中ING4 基因启动子的甲基化状态及其临床意义

目的：探讨卵巢上皮癌中ING4 基因启动子的甲基化状态及其临床意义。方法：收集2005 年7 月至2012 年6 月哈尔滨医科 大学附属第一医院行全面分期手术并经病理检查确诊的150 例卵巢上皮癌组织标本,并以同期因子宫肌瘤或子宫腺肌症行子宫 全切除术或次全切除术并经病理检查确诊为正常卵巢组织的150 例标本作为对照组。采用甲基化特异性PCR（MSP）技术检测卵 巢上皮癌组织与正常卵巢组织中ING4 基因启动子的甲基化状态,蛋白印迹法检测ING4 蛋白的表达,并分析ING4 基因启动子 的甲基化状态与卵巢上皮癌临床病例特征的关系。结果：卵巢上皮癌组织中ING4 基因启动子的甲基化阳性率为42.7%（64/150）, 明显高于正常卵巢组织（4%,6/150）,差异有统计学意义（P<0.05）。ING4 基因启动子甲基化阳性的卵巢上皮癌组织中ING4蛋白 表达阴性或弱阳性;ING4 基因启动子甲基化阴性的卵巢上皮癌和正常卵巢组织中ING4 蛋白表达阳性;在64 例ING4 基因启动 子甲基化的卵巢上皮癌组织中,ING4 蛋白表达强度与ING4 基因启动子的甲基化程度呈负相关（r=-0.435,P<0.05）。卵巢上皮癌 组织中,ING4 基因甲基化的阳性率随着手术病理分期和组织学分级的增加而增加（P<0.05）;卵巢透明细胞癌（55.6%,10/18）和卵 巢子宫内膜样癌（59.3%,16/27）中ING4 基因甲基化的阳性率显著高于浆液性囊腺癌（33.9%,20/59）和粘液性囊腺癌（39.1%, 18/46）（P<0.05）;ING4基因启动子的甲基化状态与患者的年龄、有无腹水及淋巴结转移均无显著相关性（P>0.05）。结论：ING4 基 因启动子的甲基化可能促进了其在卵巢上皮癌组织中的表达失活,进而促进了卵巢上皮癌的生长和分化。     

Binary Responses and the Three-period Cross-over

Problems with carry-over effects in the simple two-period cross-over have lead to interest in more complex cross-over designs. A method for analysing the optimum two-treatment three-period design with binary response variables is given by making a simple extension to Gart's logistic model. The method gives independent tests for, and estimates of the difference in treatment and first-order carry-over effects. An example of the analysis is given, using the loglinear models facility in GLIM.     

Hepatocellular cancer therapy in patients with HIV infection: Disparities in cancer care,trials enrolment,and cancer-related research

In the highly active antiretroviral therapy (HAART) era, hepatocellular carcinoma (HCC) is arising as a common late complication of human immunodeficiency virus (HIV) infection, with a great impact on morbidity and mortality. Though HIV infection alone may not be sufficient to promote hepatocarcinogenesis, the complex interaction of HIV with hepatitis is a main aspect influencing HCC morbidity and mortality.Data about sorafenib effectiveness and safety in HIV-infected patients are limited, particularly for patients who are on HAART. However, in properly selected subgroups, outcomes may be comparable to those of HIV-uninfected patients. Scarce data are available for those other systemic treatments, either tyrosine kinase inhibitors, as well as immune checkpoint inhibitors (ICIs), which have been added to our therapeutic armamentarium. This review examines the influence of HIV infection on HCC development and natural history, summarizes main data on systemic therapies, offers some insight into possible mechanisms of T cell exhaustion and reversal of HIV latency with ICIs and issues about clinical trials enrollment. Nowadays, routine exclusion of HIV-infected patients from clinical trial participation is totally inappropriate, since it leaves a number of patients deprived of life-prolonging therapies.     

广西竹叶青蛇伤的临床特征探讨

目的探讨广西竹叶青蛇伤后的临床特征,为临床诊治提供较合理依据。方法选择被竹叶青蛇咬伤的急诊患者55例的临床资料并分析临床特征。结果 55例竹叶青蛇伤患者分别按咬伤地点与临床分型比较(χ2=18.03,P0.01),竹叶青蛇属(竹叶青和白唇竹叶青)与临床分型比较(χ2=24.67,P0.01)及咬伤地点与竹叶青蛇属比较(χ2=24.80,P0.01),差异均有统计学意义,咬伤地点与竹叶青蛇属呈中度正相关(rs=0.67);竹叶青蛇咬伤按临床分型比较血液学变化有统计学意义(均P0.01),其中血小板(PLT)、白细胞(WBC)各型比较均有统计学意义(P0.05)。结论竹叶青蛇伤主要在城市花园草丛、田间地头等地点发生,伤后临床分型绝大多数为轻型,少数为重型和危重型;白唇竹叶青蛇伤地点主要在深山老林,伤后临床分型以危重型、重型为主,少数为轻型。咬伤地点与临床分型和蛇种属有很大差异性,可为临床诊治提供参考依据。竹叶青蛇伤致血液功能障碍,甚至出现类DIC;除分型标准外,患者WBC的增高程度可作为严重程度的参考指标。     

中国的炭疽杆菌DNA分型及其地理分布

炭疽广泛分布于中国各地,特别是西部地区,并经常造成人畜疾病,在一项合作研究中,用多位点VNTR分析（MLVA）对从1952-1998年自中国主要地理流行区域分离的病人,病畜和土壤等来源的炭疽杆菌进行了基因分型,MLVA分析结果揭示了21种新的基因型,其等位基因组合在以前世界范围分离物的研究中未曾发现,此外,分离物的分群显示,A3b组是地理上最广泛分布的基因组,说明该组可能是中国的“地方流行株”。而来自古丝绸之路重要贸易中心新疆的大量分离株其基因型特别分散。