代谢综合征与卒中

代谢综合征（metabolic syndrome，MS）是以中心性肥胖、糖尿病或者糖调节受损、高血压、血脂异常为主要内涵，以胰岛素抵抗为共同病理生理基础的临床症候群。临床医师针对代谢综合征对卒中发生、发展、转归的影响等方面的研究越来越多，本文就代谢综合征对卒中发生、再发及预后的影响等方面的研究做一回顾。     

CYP2C9/2C19基因多态性与苯妥英抗癫痫个体剂量差异的关系

苯妥英（PHT）为临床上最常用的第一线抗癫痫药，但个体间对PHT代谢呈现较大差异。目前证实细胞色素氧化酶P450（CYP）2C9／19是体内参与PHT羟化的主要代谢酶。人群CYP2C9／19遗传基因呈多态性，从而引起对PHT代谢个体间较大差异，部分人群对PHT呈强代谢（EM）。另一部分人群呈弱代谢（PM），了解这些知识对和药十分重要。本试对该方面内容进行综述。     

与氯氮平临床效应有关的遗传因素

本综述了可能影响氯氮平临床效应的遗传因素，包括代谢的遗传差异，在体内运输分布的遗传差异以及作用靶的遗传差异三个方面。     

双相障碍伴发代谢综合征与细胞因子关系的研究进展

双相障碍是一组具有高发病率、高致残率、高病死率的重性精神障碍，其中共病代谢综合征会导致更多不良的临床预后。迄今为止，两者之间的病理生理机制尚不清楚。目前的很多研究发现，双相障碍、代谢及免疫炎症之间存在联系。本文拟从肿瘤坏死因子-α、脑源性神经营养因子、抗炎性细胞因子及脂肪因子等方面对双相障碍伴发代谢异常的相关研究进行综述，以期为探索双相障碍伴发代谢综合征的早期监测指标提供初步依据。     

PET在神经外科临床应用简介

ＰＥＴ在神经外科临床应用简介胡小吾周晓平王文仲正电子放射断层显像术（ｐｏｓｉｔｒｏｎｅｍｉｓｓｉｏｎｔｏｍｏｇ－ｒａｐｈｙ，ＰＥＴ）能从生化、代谢、血流灌注、化学递质及神经受体等功能方面对病灶进行显像，目前已广泛应用于神经外科临床。本文对这方面应用进...     

代谢组学在代谢性脑血管病中的应用研究

脑血管病是全球范围内导致人类死亡和残疾的主要原因,其中很高比例与代谢紊乱相关。代谢性脑血管病是指由传统代谢危险因素和残余代谢危险因素导致的脑血管损害,以血管结构受损及功能障碍为主要病理生理学表现,干预代谢危险因素可有效改善预后的一种临床综合征。代谢组学是采用高通量组学技术对所有代谢物进行鉴定和定量的手段,是未来研究代谢性脑血管病的重要抓手。本文总结了代谢组学、脂质组学在代谢性心脑血管疾病方面的研究,旨在为代谢性脑血管病的代谢组学研究开展及其临床防治提供参考。     

骨组织形态计量学在临床骨病应用中的研究与进展

谢性骨病发生发展机制、抗骨质疏松症药物等研究。 目的：从骨组织形态计量学被认识到临床研究、临床应用以及展望进行综述。 方法：由第一作者分别以“骨组织形态计量学，骨活检，代谢性骨病，骨重建，骨结构，人”和“Bone histomorphometry，metabolic bone diseases，bone biopsy，bone remodeling，humans”为关键词进行检索，CNKI 数据库的检索时限为2000/2010，PubMed 数据库的检索时限为1965/2010。筛选骨组织形态计量学方面的文献，最终纳入30 篇文献进行分析。 结果与结论：骨计量学可得到三维的骨结构和重建的参数，在评估、提供骨代谢信息方面是一个功能强大的工具，其他任何研究方法不可代替。对于各种各样的骨代谢疾病，可从骨计量学方面更深层了解骨病的发生发展机制，为治疗提供更可靠的依据。此外，在临床新的药物安全干预、研究试验中，它提供了宝贵的骨结构和重建的参数资料。     

药物体外吸收、分布、代谢和排泄筛选模型

药物在吸收、分布、代谢和消除过程中具有良好的药代动力学性质和较低的毒副作用是候选药物通过临床试验的关键所在。这就需要合理的体外模型来对药物的体内行为进行预测。总结已有的、用于研究药物的吸收、分布、代谢、消除和药物毒性，基于细胞水平的体外模型。目前药物肠吸收的模型主要有动物体内实验和使用人造细胞膜、细胞系及肠组织的体外实验；药物分布模型包括药物与血清蛋白结合模型、药物向各组织分布的模型及透血脑屏障模型；药物代谢包括代谢稳定性、药物相互作用及药物毒性几方面。     

肌萎缩侧索硬化-额颞痴呆:基因、分子标志物及代谢

肌萎缩侧索硬化（ALS）是累及脑和脊髓运动神经元的神经退行性疾病,认知功能障碍增加了其临床异质性,来自流行病学、临床、遗传、及代谢方面的证据表明其与额颞痴呆（FTD）属于同一疾病谱;ALS-FTD目前被认为是一种重要的痴呆综合征,对其诊断和治疗提出了挑战。本文主要围绕ALS-FTD的临床特征、常见致病基因、分子标志物及代谢特征作一综述。     

氯氮平体内代谢机制的研究进展

本文对影响氯氮平血药浓度的因素、氯氮平体内代谢的途径和相关的催化酶以及药物的临床疗效、副反应等方面进行近年文献综述。     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

血浆谷胱甘肽过氧化物酶研究进展

谷胱甘肽过氧化物酶（glutathione peroxidases,GPX）是在哺乳动物中发现的,可通过还原性谷胱甘肽催化还原过氧化物和有机过氧化氢物,从而保护细胞和其他如DNA、蛋白及脂质体等敏感生物分子免受氧自由基的损伤。血浆谷胱甘肽过氧化物酶（GPx-3）是1987年Takahashi等从人的血浆中纯化得到的,是目前已知的GPX家族8个成员中唯一的细胞外亚型。研究发现有多种因素影响GPx-3的表达,并参与了多种疾病的发生、发展,本文就GPx-3的结构、功能、基因表达及其与疾病的关系作一综述。     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.     

Total saponins of Panax ginseng effects on proliferation and differentiation of human embryonic neural stem cells and in a Parkinson’s disease mouse model

BACKGROUND： Total saponins of Panax ginseng （TSPG） exhibits neuroprotection against Parkinson＇s disease in the substantia nigra. OBJECTIVE： To investigate the effects of TSPG on human embryonic neural stem cells （NSCs） proliferation and differentiation into dopaminergic neurons using in vitro studies, and to observe NSC differentiation in a mouse model of Parkinson＇s disease, as well as behavioral changes before and after transplantation. DESIGN, TIME AND SETTING： In vitro neural cell biology trial and in vivo randomized, controlled animal trial were performed at the Institute of Basic Medical Sciences, Chongqing Medical University between September 2004 and December 2007. MATERIALS： TSPG （purity 〉 95%） was isolated, extracted, and identified by Chongqing Academy of Chinese Materia Medica. Recombinant human basic fibroblast growth factor （bFGF） and recombinant human epidermal growth factor （EGF） were purchased from PeproTech, USA. A total of 25 C57/BL6J mice, aged 18-20 weeks were included. Twenty were used to establish a Parkinson＇s disease model with i.p. injection of MPTP （1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine） and TSPG alone or combined with interleukin-1 （IL-1）-treated NSCs prior to transplantation into the corpus striatum. The remaining five mice were pretreated for 3 days with TSPG prior to MPTP injection, serving as the TSPG prevention group. METHODS： Primary NSCs were isolated, cultured and purified from embryonic cerebral cortex. Immunocytochemistry was employed to detect specific antigen expression in the NSCs. In vitro experiment： （1） to induce proliferation, NSCs were treated with TSPG, EGF＋bFGF, or TSPG＋EGF＋bFGF, respectively; （2） to induce dopaminergic neuronal differentiation, NSCs were treated with TSPG, IL-1, or TSPG＋IL-1, respectively. MAIN OUTCOME MEASURES： In vitro experiment： the effects of TSPG on NSCs proliferation were evaluated with flow cytometry and MTT assay. Tyrosine hydroxylase expression was determined by immunocytochemistry assay to observe effects of TSPG on dopaminergic neuronal differentiation. In vivo experiment： differentiation of grafted NSCs in the mouse brain was determined by immunohistochemical staining. Behavioral changes were evaluated by spontaneous activity frequency, memory function, and score of paralysis agitans. RESULTS： （1） NSCs were cultured and passaged for more than three passages. Immunocytochemistry revealed positive nestin staining, as well as neurofilament protein and glial fibrillary acidic protein. （2） TSPG significantly increased NSC proliferation, in particular when combined with EGF and bFGF, which was twice as effective as FGF or bFGF alone. TSPG also induced dopaminergic differentiation in NSCs, in particular when TSPG was added together with IL-1, resulting in an effect five times greater than that of IL-1 alone. （3） At day 30 following transplantation, most NSCs in the TSPG prevention group differentiated into dopaminergic neurons, and the scores of paralysis agitans, spontaneous activity, and memory function were significantly increased compared with TSPG alone or TSPG＋IL-1 groups （P 〈 0.05）. CONCLUSION： TSPG stimulated NSC proliferation, in particular when combined with FGF and bFGF. TSPG significantly induced dopaminergic neuronal differentiation of NSCs, and the effect was greater when combined with IL-1. In addition, TSPG greatly improved behavior in the Parkinson＇s disease mouse model following NSC transplantation. Following NSC transplantation, TSPG pretreatment exhibited superior efficacy over either TSPG alone or TSPG in combination with IL-1, in terms of behavioral improvements in the Parkinson＇s disease mouse model.     

Dysfunctional autophagy in Alzheimer＇s disease： pathogenic roles and therapeutic implications

Neuronal autophagy is essential for neuronal survival and the maintenance of neuronal homeostasis. Increasing evidence has implicated autophagic dysfunction in the pathogenesis of Alzheimer＇s disease （AD）. The mechanisms underlying autophagic failure in AD involve several steps, from autophagosome formation to degradation. The effect of modulating autophagy is context-dependent. Stimulation of autophagy is not always beneficial. During the implementation of therapies that modulate autophagy, the nature of the autophagic defect, the timing of intervention, and the optimal level and duration of modulation should be fully considered.     

Oxidative stress in Alzheimer＇s disease

Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.     

Targeting 13-secretase with RNAi in neural stem cells for Alzheimer＇s disease therapy

There are several major pathological changes in Alzheimer＇s disease, including apoptosis of cho- linergic neurons, overactivity or overexpression of 13-site amyloid precursor protein cleaving enzyme 1 （BACE1） and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein （AI3） production, and introduced it into the pSilenCircle vector to construct a short hairpin （shRNA） expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing AI3 protein production. We anticipate that this technique combining cell transplantation and gene ther- apy will open up novel therapeutic avenues for Alzheimer＇s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.     

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer＇s disease

Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.