摘要：Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator （CFTR） gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach： （i） first, a reverse dot-blot analysis was performed to detect mutations with regional impact; （ii） next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and （iii） finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.

摘要：indroduction: National Aids control Organisation in india implementing National AiDS control?program uses WHO’s immunological criteria to screen virological failure. Using immunological criteria to detect virological failure has to be assessed. Predicting virological failure with immunological criteria in resource limited settings had low sensitivity. Factors that influence the outcome are studied. Methods: Retrospective study in tertiary care centre for HiV and TB, Chennai, india. Out of 35,044 on ART between January 2008 and September 2009, 452 suspected immunological failures were referred. 273 screened for virological failure.?Frequency, sensitivity/specificity, positive/negative predictive values, chi-square test, odds-ratio, independent sample t test for viral load greater than 10,000 and 1000 of each immunological criterion using Epi-info and SPSS version 19. Results: 172 had virological failure (62.09%). Average age of failed was 37.33. Single criteria’s sensitivity was 60 to 84 for detecting virolological failure. Two or more criteria had specificity 55 to 79. Combination of two or more criteria increased odds ratio for virological failure. Positive predictive value was above 63 for all criteria. PPV was above 80 to the criterion all three positive. Conclusions: ART naive patients with >95% adherence the sensitivity of immunological criteria to detect virological failure is three times than earlier studies. Combination of criteria is more significantly associated with virological failure. Odds ratio doubled for two or more combination of criteria. immunological criteria is affordable/acceptable for screening virological failure, with adherence > 95% and longer the duration of ART.

摘要：Hypoxia is a typical feature of the tumor microenvironment,one of the most critical factors affecting cell behavior and tumor ***,the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor *** study reports a three-dimensional(3D)brain tumor model obtained by encapsulating U87MG(U87)cells in a hydrogel containing type i *** also documents the effect of various oxygen concentrations(1%,7%,and 21%)in the culture environment on U87 cell morphology,proliferation,viability,cell cycle,apoptosis rate,and ***,it compares two-dimensional(2D)and 3D *** comparison purposes,cells cultured in flat culture dishes were used as the control(2D model).Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase(G0 phase)/gap i phase(G1 phase)than those cultured in the 2D ***,the two models yielded significantly different cell ***,hypoxia(e.g.,1%O2)affected cell morphology,slowed cell growth,reduced cell viability,and increased the apoptosis rate in the 3D *** results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function,and can be more representative of the tumor microenvironment than 2D culture *** developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.

摘要：Malaria still threatens global health seriously *** the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors,multi-targeting inhibitors are highly desired to overcome the increasingly serious drug ***,we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule,RYL-581,which binds to multiple protein binding sites of *** simultaneously(allosteric site of type Ⅱ NADH dehydrogenase,Q_(o) and Q_(i) sites of cytochrome bc_(1)).Antimalarials with such multiple targeting mechanism of action have never been reported ***-581 kills various drug-resistant strains in vitro and shows good solubility as well as in vivo *** structurebased strategy for designing RYL-581 from starting compound may be helpful for other medicinal chemistry projects in the future,especially for drug discovery on membrane-associated targets.

摘要：目的:确定可在冠心病患者中检测侧支循环供血心肌的磁共振灌注成像(MRPi)造影剂局部延迟。设计和机构:观察性研究、病例系列;单中心、大学医院。

摘要：背景:海地一家自服药结核病诊所。 目的:探讨在发展中国家,是否只有采用直接观察下的治疗才能帮助解决服药顺从性问题。 设计:把病人随机分为3组:A组:从药品监察器取药品,并在监察记录上给予忠告;B组:从药品监察器取药品,在记录上未得到忠告;C组:从简单的容器中取药。 结果:在前11周,监察记录良好是已经预料到的,治疗丢失者很少(P<0.01),并且在后9个月中,顺从性很好(P<0.01)。研究表明,在监察记录上给予忠告可使放弃治疗者减少约一半。 结论:本研究提示,在不能全程实行直接观察下治疗的地区,对自服药的药品监察是有效的,特别是在农村地区。其用处为:1)明确地鉴定出治疗顺从性差的病人;2)减少诊所对服药监察记录良好,居住远离诊所病人的访视频度;3)把监察记录告知病人,以改善治疗顺从性;4)当发现不合作时,可以延长其治疗期。

摘要：背景：黄斑转位术包括手术摘除年龄相关性黄斑变性（AMD）患者的脉络膜新生血管膜并将中心凹区神经视网膜移位至邻近的视网膜色素上皮上。目的：确定对于AMD继发的中心凹下脉络膜新生血管形成（CNV）的患者，黄斑转位联合360度视网膜切开手术是否有稳定和提高患者视力的作用。设计：本研究包括对90例患者施行标准的手术并在术后12个月内的固定时间进行随访检查。参加者：本研究中所有患者均因AMD导致的中心凹下CNV而出现视力下降。26例患者出现严重的黄斑部视网膜下出血，39例有潜伏的中心凹下CNV，25例有经典的中心凹下CNV。方法：黄斑转位术进行时间从1997年至1999年。患者于术前及术后3、6、12个月进行视力、微视野、血管造影检查和视轴评估。结果：术后12个月时，24例患者视力提高了15个字符以上，37例患者保持稳定，29例视力下降了15个字符以上。17例患者由于严重的并发症而需要做2次手术；17只眼可以观察到增殖性玻璃体视网膜病变，5只眼出现黄斑前膜，1只眼出现黄斑破孔。结论：黄斑转位术是一种技术性很强的手术。虽然术中和术后并发症的发生率较高，但对AMD继发的中心凹下CNV患者，手术在功能和解剖方面的结果都是确实有效的。

摘要：Heart failure is common in older people and its prevalence is *** Heart ＇omics＇ in AGEing（HOMAGE） project aims to provide a biomarker approach that will improve the early diagnosis of heart failure.A large clinical database,based on（1） prospective population studies or（2） cross-sectional,prospective studies or randomized controlled trials（RCTs） of patients at risk for or with overt cardiovascular disease will be constructed to determine most promising ＇omics＇-based biomarkers to identify the risk of developing heart failure and/or *** studies,patient cohorts and RCTs are eligible for inclusion in the common database,if they received ethical approval to obtain and share data and have baseline information on cardiovascular risk ***,the HOMAGE database includes 43,065 subjects,from 20 studies in eight European countries,including healthy subjects from three population studies in France,Belgium and italy（n = 7,124）,patients with heart failure（n = 4,312） from four cohorts in the UK,Spain and Switzerland and patients at high risk for cardiovascular disease（n = 31,629） in 13 *** is anticipated that more partners will join the consortium and enlarge the pooled *** large merged database will be a useful resource with which to identify candidate biomarkers that play a role in the mechanism underlying the onset and progression of heart failure.

摘要：背景：以前的血管内超声（intravascular ultrasound，iVUS）试验证实，他汀治疗可减缓或阻止动脉粥样硬化的进展，但是迄今尚无应用动脉粥样斑块体积百分比（percent atheroma volume，PAV）证实粥样硬化消退的确切证据。PAV是最严格的评价病变进展和消退的iVUS测量指标。目标：评价极高强度他汀治疗是否能逆转iVUS确定的冠状动脉粥样硬化。设计和地点：于美国、加拿大、欧洲和澳大利亚53个社区和3级保健中心进行前瞻性开标盲法终点试验（A Study to Evaluate the Effect of Rosuvastatin on intravascular Ultrasound-Derived Coronary Atheroma Burden，ASTEROiD）。应用马达驱动回撤iVUS评价基线和治疗24个月时冠状动脉粥样斑块负荷。每对基线和随访iVUS测量结果均进行盲法分析。病例：从2002年11月到2003年10月，507例患者有基线iVUS检查结果，并接受至少1个剂量的研究药物。在24个月后，349例患者具有可用于评估的系列iVUS检查结果。干预：所有患者均接受瑞舒伐他汀40ms／d强化治疗。主要观测指标：预先设定了两个一级疗效指标：PAV变化和基线最严重病变10min节段动脉粥样斑块体积变化。二级疗效指标为整个动脉标准化总斑块体积的变化。结果：平均（SD）LDL—C水平由基线时的130．4（34．3）ms／dL降至60．8（20．0）ms／扎，平均下降了53．2％（P〈0．001）。平均（SD）HDL-C水平从基线时的43．1（11．1）ms／dL升至49．0（12．6）ms／dL，平均增加了14．7％（P〈0．001）。整个血管PAV平均（SD）变化为-0．98％（3．15％），中位数为-0．79％（97．5％Ci，-1．21％～-0．53％）（与基线比较，P〈0．001）。最严重病变10min节段斑块体积平均（SD）变化为-6．1（10．1）mm^3，中位数为-5．6mm^3（97．5％Ci，-6．8～-4．0mm^3）（与基线比较，P〈0．001）。总斑块体积变化中位数降低了6．8％，平均减少了-14．7（25．7）mm^3，中位数为-12．5mm^3（95％Ci，-15．1～-10．5mm^3）（与基线比较，P〈0．001）。不良事件少见，与其他他汀试验相似。结论：应用瑞舒伐他汀40ms／d进行极高强度他汀治疗可使LDL-C平均水平达到60．8ms／dL，使HDL—C增加14．7％。这导致所有3个预先设定的iVUS斑块负荷指标均显示动脉粥样硬化消退。因此，将LDL-C降至低于目前指南规定的水平，同时显著提高HDL-C，可以使冠心病患者动脉粥样硬化斑块消退。这些变化对临床预后的影响尚需进一步研究确定。