多西环素多克隆抗体的制备及鉴定

目的:采用人工偶联方法构建多西环素完全抗原,制备多克隆抗体。方法:分别采用直接偶联法、甲醛一步法、重氮法+混合酸酐法和重氮法+碳二亚胺法等4种方法将多西环素与牛血清白蛋白(bull serum albumin,BSA)或鸡卵清蛋白(ovalbumin,OVA)分别偶联,构建人工完全抗原。选择最好偶联效果制备的抗原免疫BALB/c小鼠,通过直接ELISA法检测多克隆抗体效价,竞争抑制ELISA法分析其灵敏性及特异性。结果:重氮法+碳二亚胺法偶联的多西环素人工完全抗原效果最好,其与BSA的偶联比为8.37∶1,与OVA的偶联比为4.92∶1。采用该方法偶联的抗原免疫小鼠获得的多克隆抗体效价在1∶8 000以上;该抗体对多西环素的半数抑制浓度(IC50)为98.89~120.32μg/L,与其他四环素类药物的交叉反应性较低。结论:重氮法+碳二亚胺法的偶联效率最高,获得的多西环素多克隆抗体效价较高,特异性和灵敏度均较理想。     

平阳霉素联合透明质酸钠对人淋巴管畸形内皮细胞的作用

目的探讨平阳霉素(PYM)联合透明质酸钠(HA)对体外培养的人淋巴管畸形内皮细胞(HLMECs)的作用。方法对新鲜婴幼儿淋巴管畸形组织进行HLMECs原代培养。利用淋巴管内皮特异性标志物LYVE1和PROX1染色,将不同浓度(1、10、100、500μg/m L)的PYM和(50、100、300、500μg/m L)HA分别作用于HLMECs 12、24、48 h,观察对HLMECs增殖的影响并筛选其最适有效浓度。然后用该有效浓度的PYM和HA共同作用于HLMECs,在第24小时时,MTT法检测细胞生长情况,TUNEL法检测细胞凋亡情况。结果 1淋巴管畸形组织和HLMECs表达LYVE1和PROX1;2PYM的最适浓度为10μg/m L,HA的最适浓度为100μg/m L;3PYM联合HA在抑制细胞增殖和促进细胞凋亡方面比单纯的PYM作用强。结论 PYM联合HA有望在临床上用于治疗淋巴管畸形。     

实验动物品系数据库的建立

目的基于国内外部分实验动物数据库和文献,收集整理世界上现有的200多种共计26 000多个品系的实验动物数据,建立关系型检索数据库,使其成为世界上最大最全的实验动物品系数据库。方法构建基于My SQL数据库软件的中小型数据库,建立检索界面、录入界面和数据库接口。结果本文建立了实验动物品系数据库,已经收录小鼠品系数据21 596条;大鼠品系数据2062条;猴品系数据13条;地鼠品系数据2条;犬品系数据5条;兔品系数据5条。以后会逐步完善数据,实现实验动物品系数据库的定期更新。讨论该数据库的建立方便我国科研人员查阅和使用国内外实验动物品系资源,为引进欧美日等发达国家的实验动物品系资源提供链接。     

定标活检术在肠道黏膜中临床应用价值的探讨及分析

目的 评价定标活检术在肠道黏膜中的应用价值.方法 选择行肠镜检查的患者89例,使用一次性定标活检钳在其肠道黏膜进行标记,通过定期复查肠镜,分析单次标记成功率、标记的存在情况、标记局部黏膜的组织反应及其并发症等情况.结果 89例患者中单次定标成功率84.27％,总有效率96.63％.随访超过6个月、12个月、1 8个月和24个月的患者中,定标总有效率分别为82.35％、78.56％、76.54％和67.89％.结论 定标活检术在肠道黏膜中具有标识清晰,留存时间较长,适合肠道疾病的纵向对比研究,临床推广意义较大.     

Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality

Objectives Drug repurposing, which finds new indications for existing drugs, has received great attention recently. The goal of our work is to assess the feasibility of using electronic health records (EHRs) and automated informatics methods to efficiently validate a recent drug repurposing association of metformin with reduced cancer mortality.Methods By linking two large EHRs from Vanderbilt University Medical Center and Mayo Clinic to their tumor registries, we constructed a cohort including 32 415 adults with a cancer diagnosis at Vanderbilt and 79 258 cancer patients at Mayo from 1995 to 2010. Using automated informatics methods, we further identified type 2 diabetes patients within the cancer cohort and determined their drug exposure information, as well as other covariates such as smoking status. We then estimated HRs for all-cause mortality and their associated 95% CIs using stratified Cox proportional hazard models. HRs were estimated according to metformin exposure, adjusted for age at diagnosis, sex, race, body mass index, tobacco use, insulin use, cancer type, and non-cancer Charlson comorbidity index.Results Among all Vanderbilt cancer patients, metformin was associated with a 22% decrease in overall mortality compared to other oral hypoglycemic medications (HR 0.78; 95% CI 0.69 to 0.88) and with a 39% decrease compared to type 2 diabetes patients on insulin only (HR 0.61; 95% CI 0.50 to 0.73). Diabetic patients on metformin also had a 23% improved survival compared with non-diabetic patients (HR 0.77; 95% CI 0.71 to 0.85). These associations were replicated using the Mayo Clinic EHR data. Many site-specific cancers including breast, colorectal, lung, and prostate demonstrated reduced mortality with metformin use in at least one EHR.Conclusions EHR data suggested that the use of metformin was associated with decreased mortality after a cancer diagnosis compared with diabetic and non-diabetic cancer patients not on metformin, indicating its potential as a chemotherapeutic regimen. This study serves as a model for robust and inexpensive validation studies for drug repurposing signals using EHR data.     

Automated clinical trial eligibility prescreening: increasing the efficiency of patient identification for clinical trials in the emergency department

Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials.Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed.Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches.Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials.     

Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome

Purpose

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m²) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

圆柱螺旋弹簧横向刚度的计算方法

刚度是弹簧最重要的性能指标之一。圆柱螺旋弹簧的刚度分为纵向刚度和横向刚度两种。目前对于纵向刚度的研究较为深入,能够实现精确的计算,但对横向刚度的研究均是在假设和近似的前提下进行的,得到的横向刚度近似为常数,这与实际不吻合。本文针对横向受载的圆柱螺旋弹簧进行研究,通过力学分析建立了横向刚度的计算模型,并结合一个计算实例研究了圆柱螺旋弹簧的各参数对横向刚度的影响规律,得出具体的变化曲线,并对这些曲线进行了分析。     

内啮合齿轮泵月牙板与齿面间的润滑性能

内啮合齿轮泵在工业实际中应用广泛,固定月牙块与外齿轮齿面间的润滑性能是其性能的重要方面。本文构建了能够对内啮合齿轮泵月牙板与齿面间流体润滑的数值计算模型,选取LL4724型内啮合齿轮泵为对象进行数值计算研究,系统研究了压油腔压力、齿顶间隙、小齿轮转速等因素对小齿轮齿顶与月牙板下表面之间的油膜压力分布及周向流量的影响规律,得出了具体的规律性曲线,并对这些曲线进行了分析。     

双列球面滚子轴承力学分析及滚子受载计算方法

以球面滚子轴承为研究对象,运用切片法,综合考虑了滚子 滚道凸度以及轴承内圈倾斜角的影响,建立了滚子并排和滚子错排的球面滚子轴承滚子载荷的计算模型。数值计算了内圈倾斜角、径向游隙、滚子错排角、以及外载荷等参数对球面滚子轴承滚子载荷和轴承内圈径向位移量的影响。计算结果表明,在一定的外载荷作用下,轴承内圈倾斜角度与滚子最大载荷呈线性变化规律;错排滚子的球面滚子轴承最大滚子载荷比并排略小,内圈径向位移量也略小。