临床生物化学与检验教育史话

临床生物化学与检验是在对人体正常、病理状况的生理生化变化过程认识的基础上,通过分析人体标本为疾病的诊断和治疗提供有用的信息。其课程主要内容包括糖类、脂类、核酸、蛋白质、酶、激素、有机小分子、血液气体、电解质、治疗性药物、临床毒物等的检测及其临床应用。临床生物化学与检验课程对临床医学和医学检验专业学生非常重要。本文对临床生物化学与检验课程建设的历史和现状进行了总结。     

Design,synthesis and biological evaluation of novel 6H-benzo[c]chromen-6-one,and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives as potential cholinesterase inhibitors

Hydroxylated 6H-benzo[c]chromen-6-one derivatives (i.e., urolithins) are the main bioavailable metabolites, and biomarkers of ellagitannins present in various nutrition. Although these dietaries, the sources of urolithins, are employed in folk medicine as cognitive enhancer in the treatment of Alzheimer’s Disease, urolithins have negligible potential to inhibit acetylcholinesterase and butyrylcholinesterase enzymes, the validated targets of Alzheimer’s Disease. Therefore, within this research, a series of 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives has been designed, synthesized, and their biological activities were evaluated as potential acetylcholinesterase and butyrylcholinesterase inhibitors. The compounds synthesized exerted comparable activity in comparison to rivastigmine, galantamine, and donepezil both in in vitro and in vivo studies.     

Synthesis, β-haematin inhibition,and in vitro antimalarial testing of isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various substituents at C2, C6, and N11

A series of indolo[3,2-c]quinolines were synthesized by modifying the side chains of the ω-aminoalkylamines at the C6 position and introducing substituents at the C2 position, such as F, Cl, Br, Me, MeO and NO₂, and a methyl group at the N11 position for an SAR study. The in vitro antiplasmodial activities of the derivative agents against two different strains (CQS: NF54 and CQR: K1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that compounds 6k and 6l containing the branched methyl groups of 3-aminopropylamino at C6 with a Cl atom at C2 exhibited a very low cytotoxicity with IC₅₀ values above 4000 nM, high antimalarial activities with IC₅₀ values of about 11 nM for CQS (NF54), IC₅₀ values of about 17 nM for CQR (K1), and RI resistance indices of 1.6. Furthermore, the compounds were tested for β-haematic inhibition, and QSAR revealed an interesting linear correlation between the biological activity of CQS (NF54) and three contributing factors, namely solubility, hydrophilic surface area, and β-haematin inhibition for this series. In vivo testing of 6l showed a reduction in parasitaemia on day 4 with an activity of 38%.     

一粒系小麦遗传多样性分析及抗病性鉴定

一粒小麦是普通小麦种质改良的重要资源。为了从一粒小麦中发掘有用基因,选取了100对位于普通小麦(Triticum aestivum,2n=6x=42,AABBDD)A染色体组上的SSR标记,对34份一粒小麦材料进行了遗传多样性分析,并对其进行了白粉病及叶锈病的抗病性鉴定。结果表明,有69对标记在34份一粒小麦上检测出多态性,这些多态性位点包括670个等位变异,每个位点上有3~19个变异,平均每个位点上的变异为10个,位点多态性信息量(PIC)变幅为0.167~0.936,平均为0.694。通过聚类分析,将这些材料分为3个类群。通过对这些材料进行抗病性分析,共鉴定出15份抗小麦白粉病材料,21份抗小麦叶锈病材料,12份兼具白粉病及叶锈病抗性材料。这些研究结果表明:一粒小麦材料中蕴含了丰富的遗传变异,抗病材料丰富,可以作为普通小麦遗传改良的重要基因资源。     

Haloperidol treatment at pre-exposure phase reduces the disturbance of latent inhibition in rats with neonatal ventral hippocampus lesions

Animals with neonatal ventral hippocampal lesions develop during or after adolescence abnormal behaviors related to schizophrenia such as anxiety and latent inhibition disruption. The aim of this study was to test whether haloperidol injection prior to pre-exposure session in the latent inhibition test would facilitate latent inhibition.     

甲胎蛋白异质体分离方法的优化

目的:优化现有的甲胎蛋白异质体(AFP-L3)分离和检测方法,找到一个最有效的AFP-L3的提取方法,为今后的AFP-L3研究奠定前期基础。方法:应用北京热景生物技术公司的甲胎蛋白异质体(AFP-L3)亲和吸附离心管,通过改变亲和介质使用量和洗脱液体积的配伍梯度变化来优化实验流程,排除提取AFP-L3的影响因素,分离血清中的AFP-L3,并用罗氏公司的甲胎蛋白检测试剂盒检测分离的效果。结果:发现在不改变亲和介质体积的情况下,随着洗脱液体积的减少AFP-L3回收浓度逐渐增加,且在75 ul洗脱液时能够获得最高AFP-L3回收浓度。结论:成功地优化了北京热景生物技术公司的甲胎蛋白异质体(AFP-L3)亲和吸附离心管及其配套试剂的使用方法。     

Study on constant–step stress accelerated life tests in white organic light‐emitting diodes

In order to obtain reliability information for a white organic light‐emitting diode (OLED), two constant and one step stress tests were conducted with its working current increased. The Weibull function was applied to describe the OLED life distribution, and the maximum likelihood estimation (MLE) and its iterative flow chart were used to calculate shape and scale parameters. Furthermore, the accelerated life equation was determined using the least squares method, a Kolmogorov–Smirnov test was performed to assess if the white OLED life follows a Weibull distribution, and self‐developed software was used to predict the average and the median lifetimes of the OLED. The numerical results indicate that white OLED life conforms to a Weibull distribution, and that the accelerated life equation completely satisfies the inverse power law. The estimated life of a white OLED may provide significant guidelines for its manufacturers and customers. Copyright © 2014 John Wiley & Sons, Ltd.     

宏基因组学与动物病原微生物检测

宏基因组学（ metagenome）是直接从土壤、海水、人及动物胃肠道、口腔、呼吸道、皮肤等环境中获取样品DNA,利用载体将其克隆到替代宿主细胞中构建宏基因文库,以高通量检测为主要技术来研究特定环境中全部微生物的基因组及筛选活性物质和基因的新兴学科。利用宏基因组学技术不仅能够有效地检测特定环境的微生物群落结构,扩展了微生物资源的利用空间,发展了新兴的高通量检测技术,丰富了生物信息学内容。基于宏基因组学研究方法在环境微生物研究中的优势,对近年来相关领域、方法及其在人及动物病原微生物研究中的应用进行综述,以期将此方法用于实验动物病原微生物的调查分析及动物疫情、生物安全的监测。     

嗜肺巴斯德杆菌研究进展

嗜肺巴斯德杆菌(Pasteurella pneumotropica)是一种条件致病菌,人兽共患。主要危害啮齿类动物,特别是免疫缺陷或抑制的动物,可引起炎症和脓肿等症状。该菌是实验动物中感染率最高的病原菌之一,多呈隐性感染,给动物实验带来了极大的干扰。本文针对嗜肺巴斯德杆菌的流行病学、检测和鉴定、分子分型和防治等方面进行综述。