温故创新任重道远

新世纪的第一个10年,回顾神经科学基础与临床研究所走过的历程,10年进展可圈可点.在基础研究方面,蛋白质组学已成为后基因组时代研究的重要组成部分,是当今生命及生物学技术最活跃、最前沿、应用最广泛的研究领域之一.自2003年正式启动国际"人类蛋白质组计划"以来,国家将"功能基因组和蛋白质组"研究纳入"十一五"科学技术发展规划,成为生物和医药领域4项重大研究项目之一[1],不仅推动了我国蛋白质研究的深入发展,而且有助于了解帕金森病和阿尔茨海默病等中枢神经系统变性疾病的发病机制和发现具有应用前景的生物学标志.     

VR技术在构建AD患者视空间障碍的数字化诊断标志物体系中的价值

<正>阿尔茨海默病(Alzheimer’s disease, AD)是构成全球重大社会和经济威胁的中枢神经系统退行性疾病之一，早期识别、诊断和干预是其预防的关键。传统的以临床经验和生物学标志物为依据的AD诊断体系存在储备的局限。随着虚拟现实技术(VR)等可穿戴设备的不断发展，AD“数字化生物标志物”诊断体系正在形成。本文将重点阐述VR技术在早期识别、预警、诊断AD时的研究进展，并展望其在未来AD防治中的应用前景。     

帕金森病早期诊断的生物学标志物

帕金森病是一种慢性进行性中枢神经系统退行性疾病.早在临床前期尚未出现典型临床症状时,帕金森病患者即已出现神经系统退行性病变.因此,如果能在退行性病变早期及时明确诊断并予以治疗,将会减缓疾病进程,提高患者生活质量.虽然目前尚未发现早期诊断帕金森病的理想标志物,但是已有许多生物学标志物具有研究和应用前景.     

脑脊液中神经系统疾病的生物标志物

蛋白质组学（proteomics）技术是采用高分辨率的蛋白质分离手段及高效率的蛋白质鉴定技术，全景式的研究各种特定环境下的人类蛋白质的表达，是后基因组时代的重要技术。蛋白质组学研究主要有两种：组成蛋白质组学，是研究一种组织或细胞基因组的表达的所有蛋白质；另一种是比较蛋白质组学，主要是鉴定不同种类和状态下各种样本之间蛋白质的表达，比较蛋白质组学在临床医学中应用价值巨大。对重大疾病的比较蛋白质组学的研究，可以有助于疾病的早期诊断，预测疾病的转归、检测病情的变化，了解疾病的病理生理过程、寻找新的药物靶点、观察疗效。脑脊液存在于脑室系统，被认为是脑和脊髓的淋巴，正常脑脊液含有极微量的蛋白质，且绝大部分为白蛋白，球蛋白仅有微量，在发生某些疾病如：颅内感染、脑出血、脑肿瘤、中毒性脑病时，脑脊液可发生不同程度的质变和量变，且多为球蛋白，近年来国外应用蛋白组学技术对神经系统疾病患者脑脊液行特异性蛋白标志物检测，探索找到这种疾病的理想的生物标志物，应能代表这种疾病的基本发病机制，其合理性应能被神经病理学所证实，生物标志物在诊断这种病时敏感性和特异性较高，具备可行性和无侵害性。     

蛋白质组学在肝脏疾病中的研究进展☆

学术背景：蛋白质组学技术的快速发展和广泛应用,为寻找肝病的特异性标志物提供了值得探索的有效手段。近年来在肝脏的相关研究中,许多有潜在价值的标记物相继被发现。 目的：综合分析蛋白质组学在肝脏发育、再生及疾病中的研究进展。 检索策略：应用计算机检索Medline1995-01/2007-07有关蛋白质组学与肝脏疾病关系的文章,检索词为“proteomics,liver”,限定文章语言种类为English。同时计算机检索CNKI数据库1995-01/2007-07 有关蛋白质组学与肝脏疾病关系的文章,检索词“蛋白质组,肝脏”,限定文章语言种类为中文。对资料进行初审,并查找全文。纳入标准：①有关蛋白质组学的研究。②蛋白质组与肝脏疾病关系的研究。排除标准：重复研究和Meta分析。共收集到156篇有关蛋白质组学与肝脏疾病、肝移植关系的文献,纳入32篇。 文献评价：纳入的32篇文章中有关蛋白质组学研究背景的文献3篇,有关健康状态肝脏蛋白质组学研究的文献6篇,有关肝脏疾病蛋白质组学研究的文献23篇。 资料综合：蛋白质组学是指应用各种技术手段来研究蛋白质组的学科,其目的是从整体的角度研究生物机体、组织、细胞甚至细胞器基因编码的全部蛋白质,从整体水平出发的蛋白质组学研究可在更贴近生命本质的层次上去发现和理解生命活动的规律。然而目前针对肝病诊断、分期和治疗的策略十分有限。蛋白质组学技术在肝脏疾病以及肝移植的早期预警、诊断、治疗预后以及肝移植方面具有十分诱人的发展前景。 结论：随着蛋白组学在肝脏疾病中研究的不断深入,将为肝脏疾病的诊治带来一场新的革命。     

温故创新 任重道远

新世纪的第一个10年，回顾神经科学基础与临床研究所走过的历程，10年进展可圈可点。在基础研究方面，蛋白质组学已成为后基因组时代研究的重要组成部分，是当今生命及生物学技术最活跃、最前沿、应用最广泛的研究领域之一。自2003年正式启动国际“人类蛋白质组计划”以来，国家将“功能基因组和蛋白质组”研究纳入“十一五”科学技术发展规划，     

蛋白质组学在垂体腺瘤差异表达蛋白检测中的应用进展

双向聚丙烯酰胺凝胶电泳与质谱技术、生物信息学的结合,使得将蛋白质组学技术应用于临床肿瘤的研究中成为可能。比较蛋白质组学中的很多方法已经应用于肿瘤研究的不同领域。垂体腺瘤是临床常见颅内良性肿瘤,因激素分泌异常和肿瘤占位压迫引起一系列临床症状。应用比较蛋白质组学研究垂体腺瘤,发现差异表达蛋白质,并对这些差异表达蛋白质的翻译后修饰,尤其是对磷酸化修饰方面进行深入研究,有望为研究垂体腺瘤的分子发生机制、生物标志物、早期诊断和治疗提供新的思路。     

神经变性疾病脑脊液生物学标志物研究进展

中枢神经系统变性疾病是一类临床表型复杂、难以早期诊断与鉴别诊断的疾病群,发病隐匿且多呈慢性进行性发展,早期诊断、早期治疗十分关键。探寻神经变性疾病特异性的脑脊液生物学标志物,对指示或评价特定神经变性损害,以及对此类疾病的早期诊断与鉴别诊断有重要价值。本文就脑脊液生物学标志物在常见神经变性疾病(多发性硬化、阿尔茨海默病、帕金森病、肌萎缩侧索硬化症等)中的研究现状,以及对疾病诊断与鉴别诊断的辅助价值进行概述。     

蛋白质组学与器官移植

：随着质谱仪器、蛋白质和肽段的分离技术及数据分析工具的发展,不同组织、器官或细胞的蛋白质表达谱的研究也得到了迅速发展。蛋白质组学最基本的目的就是定性和定量地鉴定一个细胞或组织中的全部蛋白质。因此,如何充分利用质谱数据对蛋白质组学研究的意义很大。近几年,蛋白质组学已开始被应用到器官移植的同种异体排斥反应以及排异反应相关生物标记物的发现等领域。通过这一技术在器官移植中的广泛应用,可以早期发现及处理移植物的排异。因此,蛋白质组学的研究在器官移植排斥反应的诊断中将具有潜在的应用前景。     

双向电泳和质谱分析在神经科学研究中的应用

人类基因组计划已经完成，这一伟大的成就标志着生命科学研究进入一个新时代——后基因组时代，其中包括蛋白质组(即蛋白质组学)的研究。双向电泳和质谱技术是蛋白质组学的核心技术，将这两种技术应用于神经科学研究，能够进一步了解神经系统复杂结构及其发育规律，揭示神经系统疾病发生机理，并为其诊断和新药研制提供有益的依据。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.