生物芯片在医学中的应用进展

生物芯片是近年来发展非常迅速的一门高新技术。随着生物芯片技术研究的不断深入和完善,该技术在生物学、医学、药物学、化学工业及如农业、林业和环境保护等领域的作用越来越明显。本文就生物芯片中的基因芯片、蛋白质芯片和缩微芯片实验室在临床医学中最新的应用进展进行综述。     

基因芯片-同时研究数以千计的生物技术

基因芯片技术的出现改变了生物科学的研究方法。该技术使得从假说驱动的研究方法转变为研究后产生新的假说。再没有必要提前确定将要研究的基因或基因组。取而代之，研究人员可以检验整个基因组成一实际上是几个有机物和全部与某一特殊生物过程有关基因组，可同时被辨认。反过来与传统的研究方法做一比较，此改变同时伴随着研究术语的改变。人们不再只是简单的研究基因表达。用基因芯片，笔者现在可进行基因学研究。也就是将大量基因同时表达出来。最初，基因芯片被用于某些与基因表达有关的生物过程的研究，如细胞周期调节或疾病的分类，如癌症。然而现在随着基因芯片的普及和研究领域的增加而致费用减低，使得基因芯片技术被应用于许多新的研究领域。当今已被用于农业研究，毒素学和食品检疫等研究领域。另外，尽管基因芯片起初是被设计基因表达的检测，现在它们被用于基因突变，蛋白质表达和蛋白质功能的研究。在过去几年中，蛋白质、细胞、组织及小分子芯片相继出现，使基因芯片技术进入更广泛的研究领域。该综述意在一般性回顾基因芯片技术及其应用。重点描述与基因有关的疾病和感染性疾病。同时涉及实验设计及资料分析。     

蛋白质芯片及临床应用

人类基因组排序工作的完成是人类医学史上的里程碑。基因芯片虽可在 m RNA水平上分析整个基因组表达的情况 ,但生命活动的主体是人体内存在的 1 0万种以上的蛋白质 ,发展蛋白质芯片这一高新技术已成为生物芯片领域的挑战性课题。本文仅对蛋白质芯片的基本原理、临床应用及前景等作简单介绍     

石蜡组织芯片制备技术方法的改良

0引言生物芯片(biochips)技术包括组织芯片(tissue chips)、基因芯片(gene chips)和蛋白质芯片(protein chips)技术,这一技术方法的建立大大推动了医学及生物学领域的研究. 我室进行了组织芯片制备技术的摸索,总结出了一些行之有效的方法,并研制出了两种制备组织芯片的工具,即组织芯片空心蜡模的模具和组织芯片取样器,已获国家新型实用专利.     

多学科交叉在蛋白质点阵/芯片技术发展中的作用

蛋白质点阵／芯片技术是多学科交叉的产物，在功能蛋白质组研究方面具有广阔的潜在的应用价值。目前发展起来的印迹蛋白微阵列、分子扫描技术和传感器生物芯片质谱等技术以及生物信息学技术，将应用于药靶检测、疾病诊断、蛋白质结构鉴定和／或蛋白质之间的相互作用分析等方面，成为生命科学与医学领域的新的研究工具，极大地促进社会进步与繁荣。     

蛋白质芯片技术在肿瘤标志物筛选及鉴定中的应用

蛋白质芯片技术具有快速、并行、自动化和高通量等特点,能同时对全基因组水平上千种蛋白质进行分析,是蛋白质组学研究的重要手段。蛋白质芯片技术在揭示基因与疾病的关系上优于DNA芯片,已在研究蛋白质的性质、特征、辩识、功能及生物标志物等方面搭起快速准确的桥梁,尤其在肿瘤标志物的筛选和鉴定上取得很大进展。     

蛋白质芯片技术在营养学研究中的应用

蛋白质芯片（protein chip）技术是继基因芯片后发展起来的生物检测技术,是蛋白质组学研究中除了酵母双杂交、双向电泳技术、质谱技术等之外的一种重要的工具。利用这项技术可同时对多种蛋白质进行检测分析,使用常规方法需上千次才能完成的分析在蛋白质芯片上仅需一次就可以完成,并且检测到的平行数据误差更小,更准确,这对于高通量基因表达的研究具有非常重要的意义。     

生物芯片及其在医药领域中的应用

本文就生物芯片的概念、特点、类型和在医药领域中的应用作一简单介绍，着重介绍蛋白质芯片和组织芯片。蛋白质芯片可用于寻找疾病生物学标志物、研究蛋白质相互作用、寻找药物或毒物新靶点等；组织芯片可用于基因表达分析、寻找与临床治疗及预后有关的标志物、发现新的候选癌基因或抑癌基因等。     

蛋白组学在系统性红斑狼疮中的应用现状

蛋白组学是后基因时代出现的一门新兴科学,它是以细胞内全部蛋白质的存在及其活动方式为研究对象,其研究目的 是对机体或细胞的所有蛋白质进行鉴定,并对其结构和功能进行分析,其核心技术包括双向电泳、质谱分析、生物信息技术和蛋白质芯片技术.该文综述了蛋白组学及其研究技术,以及蛋白组学在系统性红斑狼疮（SLE）研究中的应用现状,以期为SLE的发病机制、早期诊断和治疗提供新的方向.     

毒理芯片技术在药物毒理学中的应用

近年来,生物芯片技术在生物学领域中得到了飞速的发展,并已开始用于药物毒理学领域包括基因芯片技术在药物毒理机制研究中的应用;发现毒理学中药物毒性的预测;化学物代谢特性分析与评价;化学致癌物筛选和识别,以及药物临床前安全性评价等.本文重点介绍了毒理芯片技术及其在药物毒理机制和药物毒性预测中的应用,并简单阐述了其在药物毒理上应用的局限性.     

Gene chip technology used in the detection of HPV infection in esophageal cancer of Kazakh Chinese in Xinjiang Province

Summary： This study was aimed to screen human papillomavirus （HPV） types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5＋/6＋ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/ll and G5＋/6＋, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults.     

益智健脑颗粒联合针灸对阿尔茨海默病大鼠学习记忆的影响

目的观察益智健脑颗粒联合针灸对阿尔茨海默病（Alzheimers disease,AD）大鼠学习记忆的影响。方法将大鼠随机分为假手术组（A组）、模型组（B组）、针灸组（C组）、益智＋针灸组（D组）各10只,B、C、D 3组分别以海马CA1区注射β淀粉样蛋白25-35（Aβ25-35）造模,A组注射等量的双蒸水,各组分别治疗20 d后行Morris水迷宫试验,观察大鼠学习记忆能力变化。结果B组较A组的平均潜伏期明显延长,差异具有统计学意义（P〈0.05）;与B组比较,C组、D组的平均潜伏期明显缩短,过台次数增多,差异具有统计学意义（P〈0.05,P〈0.01）;与C组比较,D组的潜伏期缩短,过台次数增多,差异具有统计学意义（P〈0.05）。结论益智健脑颗粒联合针灸能够提高Aβ25-35介导的AD模型大鼠的学习记忆能力。     

Effects of tacrolimus and cyclosporine treatment on metabolic syndrome and cardiovascular risk factors after renal transplantation: a meta-analysis

Background The therapeutic success of renal transplantation has been largely attributable to the development of effective and balanced immunosuppressive treatment regimens.This study provides a meta-analysis of a series of randomized controlled trials that compared the effects of tacrolimus and cyclosporine on metabolic syndrome （MetS） and cardiovascular risk factors after renal transplantation.Methods We searched various electronic databases and bibliographies,including MEDLINE,the Cochrane Central Register of Controlled Trials,and EMBASE,for relevant studies published prior to October 2012.Results Our meta-analysis included five randomized controlled trials that examined a total of 923 patients.The tacrolimus group and the cyclosporine group exhibited no significant differences in MetS incidence after renal transplantation; risk ratio （RR）：1.06,95％ confidence interval （C/）：0.73-1.55,P=0.76.Cyclosporine treatment was associated with a higher incidence of hyperlipidemia （RR：0.50,95％ CI：0.39-0.64,P ＜0.01）.Although there were no statistically significant differences,cyclosporine treatment was associated with a higher incidence of hypertension （RR：0.91,95％ CI：0.83-1.00,P=0.06） after renal transplantation compared to tacrolimus treatment,and tacrolimus treatment was associated with a higher incidence of diabetes after renal transplantation （RR：1.79,95％ CI：0.98-3.27,P=0.06） compared to cyclosporine treatment.Conclusions Compared to tacrolimus treatment,cyclosporine treatment was associated with a higher incidence of hyperlipidemia.Future large-scale studies are expected to be conducted to further confirm our findings.     

WHO西太区与“世界中医药学会联合会”中医名词术语国际标准比较研究：精、神、气、血、津、液部分

精、神、气、血、津、液是中医理论中6个非常重要的概念，有关术语在《WHO西太区传统医学国际标准名词术语》中一共收录了59条，“世界中医药学会联合会”（以下简称世中联）《中医基本名词术语中英对照国际标准》中收录了58条。血、津、液的内涵较为具体，有一定的物质基础，理解并不困难。翻译上虽有差异，但亦不难统一。精、神、     

Liuwei Dihuang,a traditional Chinese herbal formula,suppresses chronic inflammation and oxidative stress in obese rats

OBJECTIVE： To investigate the anti-inflammatory, anti-oxidative stress, and adipokine-ameliorating effects of Liuwei Dihuang （LWDH）, a traditional Chinese herbal formula, in obese rats. METHODS： After 2 weeks of acclimation with free access to regular rodent chow and water, obese-prone-caesarean-derived （OP-CD） rats were fed a modified AIN-93G diet containing 60% energy from fat. Treatment was performed twice daily by gavage feeding with 500, 1 500, or 3 500 mg/kg body weight LWDH suspended in water （n=12 rats per group）. Twelve obese-resistant-CD （OR-CD） rats were fed the atherogenic diet and gavaged with water, and served as the normal control. Blood biomarkers of inflammation, oxidative stress and adiponectin were measured post-sacrifice and used to determine the treatment effect of LWDH and assess the suitability of OR/OP-CD rats for studying these parameters. RESULTS： After 9 weeks of treatment, LWDH lowered serum C-reactive protein （CRP） and tumour necrosis factor-α （TNF-α） levels. Serum interleukin-6 （IL-6） levels showed a tendency towards reduction, but were not significantly different from the OP-CD control. Liver superoxide dismutase （SOD） activity was increased in response to all three doses of LWDH, while the levels of reduced （GSH） and oxidized glutathione （GSSG） and thiobarbituric acid reactive substances （TBARS） were unchanged. Serum adiponectin levels were increased in response to oral administration of LWDH at the dose of either 500 or 1 500 mg/kg body weight. In addition, comparisons between OR-CD and OP-CD rats revealed differential, and for some biomarkers, conflicting characteristics of high-fat diet-fed OP-CD rats in reference to obese human subjects in terms of inflammatory and oxidative stress biomarkers and circulating adiponectin levels. CONCLUSION： The results show, for the first time, the anti-inflammatory, anti-oxidative stress and adiponectin-ameliorating effects of LWDH in obese rats. The suitability of the OP-JOP-CD rat model as     

New Mechanism of Herb-herb Interaction between Ginseng and Trogopterus Based on CYPs in Rat Livers

The study was designed to investigate the potential mechanism of herb-herb interaction between ginseng and Trogopterus （Trg） based on Cytochrome P450 isozymes （CYPs） in rat livers. We estimated the influence on CYP1A2, CYP2E1, and CYP3A1/2 activity caused by ginseng and Trg used in combination. The CYP1A2 and CYP2E1 enzyme activity were induced by ginseng and Trg used in combination. And this induction effect was caused via inducing CYP1A2 and CYP2E1 protein expression which was supposed caused by inducing the gene expression of CYP1A2 and CYP2E1.     

表皮生长因子受体酪氨酸激酶抑制剂在非小细胞肺癌应用的瓶颈——获得性耐药

以表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI）分子靶向治疗研究为肇始,转化性研究使基础实验和临床实践间的鸿沟迅速填平,改变着人们认识治疗肺癌的视角。无可否认,EGFR-TKI上市后极大地延伸了肿瘤学家治疗肺癌的手段,但不管从临床经验、临床研究数据、分子生物学层面还是文献计量学的角度,     

Bias in multiple-treatments meta-analysis: a case on comparative efficacy and tolerability of 15 antipsychotic drugs for schizophrenia

Multiple-treatments meta-analysis is thought to be a feasible method to compare the efficacy and safety among different treatments, especially when there was no head-to-head research among some treatments. But sometimes some conclusions are inconsistent with the clinical experience. Recently, we read a multiple-treatment meta-analysis finished by Stefen Leucht et al, which was published in Lancet） The authors summarized the results of the RCT studies on 15 antipsychotics commonly used in practice; they also horizontally compared the efficacy and safety profile by the recta-analysis. We believe that the results provide more solid evidence for the rational usage of antipsychotics to the psychiatrists, also for the government to distribute health resources in a more reasonable way.     

Differential effect of calcium-activated potassium and chloride channels on rat basilar artery vasomotion

Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomotion in the cerebral basilar artery （BA） of Wistar rats. Pressure myograph video microscopy was used to study the changes in cerebral artery vessel diameter. The main results of this study were as follows： （1） The diameters of BA and middle cerebral artery （MCA） were 314.5±15.7 μm （n=15） and 233.3±10.1 μm （n=12） at 10 mmHg working pressure （P〈0.05）, respectively. Pressure-induced vasomotion occurred in BA （22/28, 78.6%）, but not in MCA （4/31, 12.9%） from 0 to 70 mmHg working pressure. As is typical for vasomotion, the contractile phase of the response was more rapid than the relaxation phase; （2） The frequency of vasomotion response and the diameter were gradually increased in BA from 0 to 70 mmHg working pressure. The amplitude of the rhythmic con- tractions was relatively constant once stable conditions were achieved. The frequency of contractions was variable and the highest value was 16.7±4.7 （n=13） per 10 min at 60 mmHg working pressure; （3） The pressure-induced vasomotion of the isolated BA was attenuated by nifedipine, NFA, 181]-GA, TEA or in Ca2＋-free medium. Nifedipine, NFA, 18~-GA or Ca2＋-free medium not only dampened vasomotion, but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction state. These results sug- gest that the pressure-induced vasomotion of the isolated BA results from an interaction between Ca2＋-activated C1- channels （CaCCs） currents and Kca currents. We hypothesize that vasomotion of BA depends on the depolarizing of the vascular smooth muscle cells （VSMCs） to activate CaCCs. Depolarization in turn activates voltage-dependent Ca2＋ channels, synchronizing contractions of adjacent cells through influx of extracellular calcium and the flow of calcium through gap junctions. Subsequent calc     

Morphometric Analysis and Microsurgical Anatomy for Far-lateral Transcondylar Approach

Objective To provide basic microsurgical anatomy parameters for the far lateral transcondylar approach. Methods Thirty dry skulls were measured around foramen magnum. Twenty formalin fixed Chinese adult cadaveric heads were employed by microsurgical dissection and the vital anatomical structure was delineated and measured. The dissection was performed imitating the far-lateral transcondylar approach. In addition, among 20 formalin fixed cadaveric heads, 10 adult cadaveric heads were scanned with Spiral CT thin tomographic scanner. Some structures of foramen magnum were measured by CT thin tomographic scan. The 3D-CT （three dimensional computed tomography） reconstruction was performed in 4 adult cadaveric heads including preoperative and post-operative. Results Occipital condyle （OC） was an important sign in the far lateral transcondylar approach and its long axis was 24.47±3.32 （18.19-30.30）mm （left,L）; 25.16±2.39 （20.66-29.02）mm （right, R） （standard deviation）. The distance from the posterior midline of the foramen magnum （FM） to the medial border of the OC was 27.66±2.45 （23.00-31.48）mm （left）; 26.27±1.83 （23.68-29.64）mm （right）. Inferior occipital triangle was formed by three muscles, which was rectus capitis posterior major, superior oblique and inferior oblique. The distance of vertebral artery from lateral side of transverse foramen of atlas to its dural entry was 16.87±2.08 （12.64-20.1）mm （left）, 16.79±1.90 （12.44-20.22）mm （right）. Some vital bone structures such as jugular foramen, hypoglossal canal, condylar canal, transverse foramen of atlas could be showed clearly on the three-dimensional reconstruction CT image. Conclusion In this study, the authors provided some anatomic parameters for far lateral transcondylar approach. They documented the structures of inferior occipital triangle and the course of vertebral artery. Rare variation of VA should be paid more attention to. The thin tomographic scan and three-dimensional construction