从临床误诊率浅谈诊断学教学改革

随着高科技的迅速发展,医学领域不断涌现出先进的诊断方法,例如基因检测已开始进入临床;器械检查更是日新月异(CT,螺旋CT,MR,DSA,血管内超声检查等),对临床诊断提供了更新、更快、更细的诊断信息,对疾病的诊断大有裨益.但是大量资料表明,新的、先进的诊断方法的出现并未带来诊断正确率的提高和(或)错误率的下降.据国内一项研究表明,导致误诊的常见原因有,医学经验不足(25%);医生问诊与体格检查不细致(17.3%):未选择特异性项目(17%);医生过分依赖或迷信辅助检查结果(14.7%).从中不难看出除了医学经验不足外,其余75%的误诊原因直接与诊断学有关.这就进一步要求诊断学的教学改革必须关注临床现实,临床高误诊率及其原因也为诊断学的教学改革指明了方向.     

肿瘤基因标志物的应用和研究进展

肿瘤基因标志物是指肿瘤组织或细胞中发生突变或者表达异常的一类基因,涉及基因组学和表观遗传学相关分子.当前,利用分子生物学技术筛选各类肿瘤基因标志物,对于辅助肿瘤早期诊断、预后判断、个体化治疗具有重要意义.此文从DNA和RNA肿瘤标志物方面,阐述近年来肿瘤基因标志物在肿瘤诊断和治疗中的应用和研究进展.     

肥厚型心肌病的分子遗传机制

家族性肥厚型心肌病是一种常染色体显性遗传病。肥厚型心肌病临床表现存在很大差异,从无症状到黑朦、晕厥、胸痛、心律失常及心力衰竭等不尽相同。很多青年患者往往平时无症状或首发症状就是猝死。已发现至少有25种基因的突变可导致家族性肥厚型心肌病。加深对其分子遗传学的认识有利于促进该病的诊断和治疗。本文对家族性肥厚型心肌病的近期分子遗传学研究进行了总结。     

先天性,遗传性疾病的产前诊断

产前诊断是近代生物学、生物化学、细胞遗传学、分子遗传学和医学实践紧密结合的一个新的课题,是近代医学的一项重大成就。应用这些技术,对可能生育或已经生育过遗传病患儿的孕妇进行检查,如观察胎儿外形、分析胎儿核型细胞的生化成份或基因组成等,进行产前诊断,使获得健康后代的理想成为现实,有利于提高各族人民的智力和体质水平。     

胞内抗体和胞内因子技术与疾病的分子治疗

胞内抗体和胞内因子技术是一种新颖的基因治疗策略,也是用于表型敲除研究的又一有力工具.胞内抗体/因子通过基因重组技术在细胞内表达并被定位于特定的亚细胞器中,能够特异性地结合细胞内靶分子,进而影响靶分子的加工或分泌过程及其生物学效应,已在人艾滋病、恶性肿瘤、移植排斥和神经变性等疾病的分子治疗领域彰显出潜在的应用前景.     

医学影像学在临床骨科医学中的应用进展

<正>在临床医学中,骨科的医学影像学研究意义非常重要,它不仅可以提高临床诊治骨科疾病的水平,而且有望在分子细胞水平发现骨科疾病,真正达到早期诊断。本文综述了医学影像学的进展对临床骨科医学的影响,现报告如下。1踝关节的医学影像诊断学应用分析1.1踝关节的常规诊断学方法:踝关节是人体常     

加强体外诊断试剂的管理工作

体外诊断试剂是指采用免疫学、微生物学、分子生物学等原理或方法制备的、在体外用于对人类疾病的诊断、检测及流行病学调查等的诊断试剂.体外诊断试剂的品种和种类繁多,以方法学分类有酶免、放免、荧光和化学发光、分子生物学、免疫组化、免疫细胞化学等,以检测对象分类有细胞水平、蛋白分子水平以及基因水平等的检测对象,以临床应用上分类有初筛、初筛后确证、诊断和疗效观察等,以所使用的技术分类有标记免疫技术、分子杂交技术、基因扩增技术等.由此可见体外诊断试剂的多样性和复杂性.     

第八届全国诊断学教学改革研讨暨学术交流会议通知

全国高等院校诊断学教学咨询委员会委托吉林大学举办第八届全国诊断学教学改革研讨暨学术交流会中心内容是实验诊断学检查规范化和编写实验诊断学教材改革研讨时间2005年8月5日至8月10,。日会议语种中英文地点吉林省长春市参加人员全国高等院校医学教学及其附属医院领导内科外,:、,:。:、、科检验科诊断学和实验诊断学教研室教学人员省市级医院和解放军驻军以上医院领导内科外科检、、,、、、、验科主任征文内容实验诊断学规范化检查的方案或设想按临床主要症状体征疾病提出包括以。:①,、、。②诊断学为主临床血液学临床化学临床病原生物学…     

肝内胆管癌病理机制表观基因组学研究进展

肝内胆管癌(ICC)是一类高侵袭性的恶性肿瘤,分子机制不明确。其治疗术后易复发且化疗不理想,目前尚无可供特异性早期诊断的生物标记物。近年来研究发现特异性的基因突变如KRAS、EGFR、IDH1和IDH2等,基因甲基化和miRNA等表观遗传学改变,IL-6/STAT,酪氨酸激酶受体相关的信号通路异常激活等参与ICC的发病和转移,其中许多关键基因成为分子靶向药物治疗靶点。我们就其病理机制表观基因组学研究进展作一综述,旨在为促进发现新的诊断和治疗ICC的生物标记物,实施联合分子靶向治疗的策略提供思路。     

神经母细胞瘤实验诊断学的重要意义

该文探讨了神经母细胞瘤（NB）实验诊断学研究,并简要介绍实验诊断学在NB临床分型、预后判断等方面的应用,以期促进人们对实验诊断学在NB诊断中作用的认识,从而提高NB临床诊断水平。     

Applied neurogenomics

Neurogenomics, the study of the genes of the nervous system, has applications in basic research, in the pharmaceutical industry and in the management of neurological disorders. Basic research applications include molecular neuropathology, the detection of genes for neurological disorders, the study of gene expression in the CNS and creation of transgenic models of neurological disorders. Pharmaceutical applications may be in the areas of molecular neuropharmacology, the discovery of new drugs for neurological disorders, gene therapy and the development of personalised medicines based on pharmacogenomics. Clinical applications in neurology include the redefinition and reclassification of diseases, molecular diagnostics and the integration of diagnostics with therapeutics. Various methods for the study of genes and gene expression are described. Genes have been identified for only a limited number of neurological disorders so far. The discovery of genes defective in neurological disorders would facilitate drug discovery, molecular diagnostics and gene therapy diseases. There is a trend towards the integration of diagnosis, genetic screening, prevention, treatment and monitoring of therapy of neurological disorders, which will be facilitated by neurogenomics. Pharmacogenomics-based personalised medicines are anticipated to be part of medical practice by the end of the first decade of the 21st century, and neurogenomics will contribute to the development of personalised medicines for diseases of the CNS.     

Determination of tumour marker genes from gene expression data

Cancer classification has traditionally been based on the morphological study of tumours. However, tumours with similar histological appearances can exhibit different responses to therapy, indicating differences in tumour characteristics on the molecular level. Thus, development of a novel, reliable and precise method for classification of tumours is essential for more successful diagnosis and treatment. The high-throughput gene expression data obtained using microarray technology are currently being investigated for diagnostic applications. However, these large datasets introduce a range of challenges, making data analysis a major part of every experiment for any application, including cancer classification and diagnosis. One of the major concerns in the application of microarrays to tumour diagnostics is the fact that the expression levels of many genes are not measurably affected by carcinogenic changes in the cells. Thus, a crucial step in the application of microarrays to cancer diagnostics is the selection of diagnostic marker genes from the gene expression profiles. These molecular markers give valuable additional information for tumour diagnosis, prognosis and therapy development.     

Challenges in current drug delivery from the potential application of pharmacogenomics and personalized medicine in clinical practice

The recent technological achievements in biotechnology and recombinant DNA technology have provided multiple new methods, molecular targets, and DNA-based diagnostics to pharmaceutical research that can be utilized in assays for screening and developing potential biotechnology-based drugs, as well as in biomedicine, health and pharmaceutical care. Furthermore, such advances opened up new opportunities by applying genetic information data in pharmacotherapy and drug delivery, thus ensuring better drug efficacy and safety in clinical practice. Now the concepts of personalized medicine and pharmacogenomics are likely improving the area of pharmacodynamics and pharmacokinetics, since they favor differentiation of the conventional clinical diagnosis and drug selection into separate molecular subtypes of individuals belonging within a group of patients suffering from the same disease. Genetic polymorphisms have already been detected and analyzed in genes encoding drug-metabolizing enzymes, transporters as well as targets (e.g. receptors). The potential of applying genotyping and haplotyping analysis in future pharmaceutical care could eventually lead to pharmacotyping, i.e. individualized drug delivery profiling based on genetic-bioinformatic data in routine patient care. However, the steps towards this direction of drug delivery in clinical practice still have a long way to go to be fully achieved; until then, the critical evaluation of all available clinical data including pharmacodynamic, pharmacokinetic and genomic must be assessed for ensuring drug efficacy and safety. In this way, there has been great progress in elucidating genetic determinants contributing to the observed interindividual differences in drug disposition and effects, thus implementing current drug delivery with molecular genetics and diagnostics.     

Applications of biochips: from diagnostics to personalized medicine

This review examines the role of advances in biochip and microarray technologies in the development of personalized medicine. Biochips (eg, GeneChip, CYP450, electrochemical biochips, protein biochips, microfluidic biochips and nanotechnology-based biochips) are assuming an important role in molecular diagnostics, and their application in point-of-care diagnosis is expected to facilitate the development of personalized medicine. Gene expression profiling by microarrays should advance the progress of personalized cancer treatment based on the molecular classification of subtypes. Refinements in biochip miniaturization with the advent of nanotechnology will further contribute to molecular diagnostics and the development of personalized medicine.     

Molecular diagnostics of viral hemorrhagic fevers

This review addresses the diagnostics of viral hemorrhagic fevers (VHFs). In the first part, an overview is given on classical methods of VHF diagnostics as well as novel molecular diagnostic tools. Currently available polymerase chain reaction (PCR) assays for diagnosis of VHF are summarized and discussed. In the second part, VHF diagnostics are described in particular for Lassa fever, yellow fever, and Crimean-Congo hemorrhagic fever, based on cases that were imported into or occurred within Europe. The third part is focussed on important differential diagnoses of VHF.     

DNA microarray technology in nutraceutical and food safety

The quality and quantity of diet is a key determinant of health and disease. Molecular diagnostics may play a key role in food safety related to genetically modified foods, food-borne pathogens and novel nutraceuticals. Functional outcomes in biology are determined, for the most part, by net balance between sets of genes related to the specific outcome in question. The DNA microarray technology offers a new dimension of strength in molecular diagnostics by permitting the simultaneous analysis of large sets of genes. Automation of assay and novel bioinformatics tools make DNA microarrays a robust technology for diagnostics. Since its development a few years ago, this technology has been used for the applications of toxicogenomics, pharmacogenomics, cell biology, and clinical investigations addressing the prevention and intervention of diseases. Optimization of this technology to specifically address food safety is a vast resource that remains to be mined. Efforts to develop diagnostic custom arrays and simplified bioinformatics tools for field use are warranted.     

Recent advances in biomarkers for cancer diagnosis and treatment

With the availability of new technologies and the increased interest of medical practitioners to use molecular biomarkers in early detection and diagnosis, and in the prediction of therapeutic treatment efficacy and clinical outcomes, the academic and research institutions, as well as the pharmaceutical industry, have increased their efforts to develop novel molecular biomarkers for several human diseases, including cancer. The identification of molecular biomarkers also enables the development of a new generation of diagnostic products and to integrate diagnostics and therapeutics. This integrated approach will aid in 'individualizing' the medical practice. Here, we address issues related to the development of biomarkers, novel technological platforms used for drug development, future technologies and strategies for validating biomarkers for their clinical utility.     

血中游离DNA与肿瘤

血中游离DNA指血中游离于细胞之外的一类DNA,简称循环核酸,于1947年由Mandel和Metais发现。肿瘤患者外周血DNA水平高于正常人且血中游离DNA具有肿瘤细胞DNA的特征,如肿瘤相关基因的突变、微卫星改变、甲基化异常和线粒体DNA突变等。随着肿瘤分子生物学的深入研究,血中游离DNA定性定量分析已开始应用于肿瘤的早期诊断、个体化治疗和预后判断等。血中游离DNA结合各类分子生物学检测技术,有望成为具有一定敏感性及高特异性的临床诊断方法。此外,血中游离DNA还有可能成为非细胞形式的肿瘤转移的新途径。     

Asuragen Inc

Asuragen is a fully integrated molecular diagnostics company with products and services that incorporate cutting-edge technologies for isolating, detecting and quantifying nucleic acids. Asuragen's Signature product line offers streamlined methods for the detection of important genetic alterations and innovative RNA-based solutions for molecular oncology. The company has also pioneered research on microRNA (miRNA) function, isolation and detection in clinical samples. Asuragen is leveraging its broad intellectual property portfolio to build a significant business focused on miRNA/mRNA molecular diagnostics and pharmacogenomic/clinical laboratory molecular services. A near-term goal is to introduce next-generation miRNA-based diagnostic assays to improve tumor classification, monitor disease progression and potentially allow earlier detection of cancer. Asuragen's miRNA therapeutics development program has recently been carved off into a new sister company, Mirna Therapeutics (TX, USA).     

大肠癌癌前疾病及癌分子诊断的研究进展

大肠癌又名结直肠癌(CRC)是国内外最常见的恶性肿瘤之一,多数发病隐匿,因而就诊者多已处中晚期,且发病率持续攀升,病死率高;癌症形成经历多步骤、多阶段、多基因参与,由腺瘤向癌的演变,因此早发现、早诊断CRC癌前疾病及CRC至关重要.目前国内外对CRC癌前疾病及癌相关分子标志物的研究日新月异,尤其CRC的基因、转录、蛋白质、代谢四大组学观点的提出.现就CRC癌前疾病及CRC分子诊断的研究进展进行阐述.