糖尿病前期是2型糖尿病发病过程中的必经阶段, 也是大血管病变和微血管病变的独立高危因素。参阅国内外相关文献, 本文通过对几个大规模糖尿病前期干预研究的分析, 概述了近年来中西医干预糖尿病前期的研究成果, 并详细论述中药干预糖代谢的有效物质基础及作用机制, 大量的临床试验和动物实验证明, 许多中药及其提取物具有良好的改善糖代谢的作用, 其有效成分主要有生物碱、黄酮等。改善糖代谢的作用机制主要为修复β细胞, 增加胰岛素分泌, 改善胰岛素抵抗等。

Prediabetes is the necessary stage of type 2 diabetes（T2DM）, and also an independent risk factor of macrovascular and microvascular diseases.Referred to the related literature at home and abroad, we analyzed several large scale studies of prediabetes intervention.This article summarized the achievements of prediabetes intervention in recent years with western and Chinese medicine.It also showed a detailed discussion on effective ingredients and mechanism of Traditional Chinese medicine in improving glucose metabolism.A large number of clinical trials and animal experiments have proved that lots of Chinese medicines and extracts showed positive effect in improving glucose metabolism.The effective components mainly include alkaloids, flavones and so on.The mechanisms are primarily through repairing beta cells, promoting insulin secretion, improving insulin resistance and so forth.

糖尿病肾病（Diabetic nephropathy, DN）是引发终末期肾衰竭的主要原因, 严重危害人类健康, 迫切需要有效的治疗方法。近年来, 我们采用循证医学的方法研究证实中医药治疗DN有一定的临床疗效, 并从整体、细胞、分子等不同层次上探讨了中医药治疗DN的作用机制, 发现单味中药及复方可以通过多靶点、多途径发挥治疗作用, 中医药有望成为治疗糖尿病肾病的有效方法之一。本文将概述近年来本领域的研究进展, 为今后的研究提供参考。

Diabetic nephropathy is the main reason of the end stage renal failure and endanger human health seriously.Effective treatment of diabetic nephropathy is in an urgent demand.In recent years, we confirmed the good effect of TCM on diabetic nephropathy by evidence based medicine method.We also explored the treatment mechanism of TCM on diabetic nephropathy from overall level, cellular level and molecular level and found that both single herb and Chinese herbal compound can treat diabetic nephropathy by multiple targets control.TCM may become one of the effective methods for treating diabetic nephropathy.This paper will review the advances in this research field of recent years and provide references for future researches.

多发性硬化（Multiple sclerosis, MS） 是一种难治性中枢神经系统脱髓鞘疾病, 其复发率及致残率高。 目前病因和发病机制不明, 目前开发的药物不能控制该疾病的发展进程。本文总结了近十年来中医药治疗MS的 临床观察和实验研究, 并分析中医药治疗MS的优势、存在的问题和今后的设想, 为MS患者提供了一条新的治疗途径。

Multiple sclerosis（MS）is a kind of refractory demyelinative disease of the central nervous system which characterized with high incidence of recrudescing and deformity. Nowadays,the etiology and pathogenesis of MS are still unknown and the course of MS cannot be controlled by drugs. Large number clinical studies found that Chinese medicine or combination with western therapy in treating MS patients showed its advantages. This article aims at summarizing the clinical observation and experimental research of traditional Chinese medicine in prevention and treatment of MS in recent ten years. The results showed that Chinese medicine could improve clinical signs and symptoms,reduce the relapse rate,regulate the immune function,reduce the side effects of hormones. Experimental studies showed that Chinese herbal compound,single herb and its active ingredients could improve the clinical symptoms of EAE animals,reducing its neurological function,reduce the immune and inflammatory damage,and had a significant n

唇形科植物丹参（Salvia miltiorrhiza Bunge）是治疗心血管系统疾病的临床常用中药, 主要含有两类有效成分：脂溶性的二萜醌类化合物和水溶性的酚酸类化合物, 具有显著的抗菌消炎、抗血栓形成、抗心肌缺血、保肝及抗氧化作用。由于直接从丹参中提取有效成分纯度低、效率低, 提取纯化困难, 加之丹参资源有限, 影响了临床用药质量和天然药物的开发与持续利用。为解决此问题, 化学及分子生物学等多种现代技术手段应用到丹参资源质量及产量的提高中, 并已取得不同程度的进展。本文从丹参活性成分的人工合成、生物技术手段的应用、次生代谢调控及次生代谢工程研究四个角度全面综述了丹参资源研究现状, 为进一步推动丹参资源开发现代化进程提供借鉴。

Salvia miltiorrhiza Bunge is a traditional Chinese medicine commonly used for the treatment of cardiovascular diseases.It contains two kinds of effective ingredients: fat soluble diterpene quinones and water soluble phenolic compounds.It shows significant effects including anti bacterial, anti inflammatory, anti thrombotic, hepato protective, and antioxidant properties and protection against myocardial ischemia.However, extraction of active components from S.miltiorrhiza directly is challenging due to low purity.Furthermore, the limited material resources of S.miltiorrhiza affect its utility in clinical medicine and the sustainable exploitation of natural drugs.In order to overcome this challenge, chemistry, molecular biology and other scientific technologies are being explored to improve the yield and quality of S.miltiorrhiza, with considerable progress made to date.Firstly, a variety of tanshinone and salvianolic acid compounds have been synthesized successfully from S.miltiorrhiza, while compounds such as tanshinone IIA have been structure modified to improve solubility and bioavailability.Secondly, biological technologies such as induction of polyploidy, cell suspension culture, and the induction of hairy roots have been developed.Hairy root of S.miltiorrhiza, which is most widely used at present, can be manufactured on a large scale and harvested using a spherical gas lifted bioreactor.Additionally, due to good genetic and chemical stability of the hairy root, it can be used as a research model for further development of S.miltiorrhiza.Thirdly, a variety of biotic and abiotic elicitors have been exploited for the study of effective components of S.miltiorrhiza, which have different effects on the plant.Appropriate combinations of these elicitors could further improve the yield of active components of S.miltiorrhiza.Finally, with the development of molecular biology, secondary metabolite engineering has become a new hotspot of medicinal plant research.S.miltiorrhiza is confirmed as a model to study terpenoid metabolism, wi

脑出血（Intracerebral hemorrhage, ICH）是我国高发的脑血管病之一, 具有发病率高、致残率高、病死率高等特点。通过对将近5年的针刺治疗脑出血相关文献的研究, 我们认为针刺在脑出血的治疗中具有一定的优越性。与单纯西药治疗相比, 针刺的辅助治疗能提高患者的神经功能评分并提高治疗有效率等。

Intracerebral hemorrhage(ICH) is one of the cerebrovascular disease which occurs frequently in China with the high rate of occurance, disability and death.Through the acupuncture in treating cerebral hemorrhage related literature study in recent 5 years, we found that acupuncture compared with the simple western medicine has certain advantages in the treatment of cerebral hemorrhage, the help of acupuncture treatment can improve the patients neurological function score and increase the effective rate.Through these datas research, we hope to provide references for further study.

抗精神病药已经有60余年的使用历史, 应用于治疗精神分裂症及其他精神疾病伴随的幻觉、妄想症等症状。临床和动物研究都提示抗精神病药的长期使用会导致个体对药物的敏感性发生变化, 即产生敏化或耐受效果。在急性用药情况下, 多种临床常用抗精神病药作用都可以抑制条件躲避反应和苯环利定诱发的运动增强。以这两个动物模型为基础, 我们建立了研究抗精神病药敏化和耐受的行为学范式。以此为基础, 我们一系列研究发现长期用药可导致药物敏感性加强或减弱, 即敏化或耐受。并进一步考察了敏化和耐受的行为学特征及其神经生物学基础。结果表明大多数抗精神病药长期用药会导致敏化, 这些药物包括：奥氮平、阿塞那平、阿立哌唑、利培酮、氟哌啶醇等, 而只有氯氮平会导致耐受。在行为学层面, 敏化和耐受在不同抗精神病药间存在迁移效应, 并且可以长期保持。在受体机制方面, 我们发现多巴胺D2受体和五羟色胺2A （5 HT2A） 受体参与调控敏化和耐受。在中枢机制方面, 发现内侧前额叶以及中脑边缘系统核团参与调控敏化和耐受。

Antipsychotics are the medications that are used to treat schizophrenia How they work to achieve their therapeutic effects has not been adequately addressed Like other psychoactive drugs, repeated administration of these drugs can induce various clinically relevant sensitization and tolerance effects in many behavioral domains.In recent years, we have used the conditioned avoidance response (CAR) and phencyclidine (PCP)induced hyperlocomotion, two models with high predictive validity for antipsychotic efficacy and examined the long term treatment effects of antipsychotic drugs.In this paper, I discuss our animal work on the behavioral characteristics and neuroreceptor mechanisms of antipsychotic sensitization and tolerance, as well as their developmental impacts from adolescence into adulthoodnI highlight our work on the roles of dopamine D2 receptors and serotonin 5 HT2A receptors in the medial prefrontal cortex and nucleus accumbens in the induction and expression of antipsychotic sensitizatio

传统的精神分裂症动物模型虽然已得到了广泛应用, 但在信度和效度上仍然存在很多问题。我们认为, 建立在多重因素整合基础上的多层次化认知障碍动物模型, 可以更好地模拟精神分裂症症状, 有望成为今后发展精神分裂症动物模型的新方向。为此, 我们尝试使用对惊反射前脉冲抑制的多层次性自上而下认知和注意调节的行为范式与多致病因素相结合来建立新一代的精神分裂症的动物模型。新的动物模型对深入了解精神分裂症的致病机制以及寻求更加有效的治疗策略都有重要的意义。

Although some traditional animal models for studying schizophrenia have been wildly used, many problems remain in their credibility and validity.We propose that structured animal models with the integration of multiple symptom inducing factors are be better in simulating the symptoms of schizophrenia and represent the new direction of the future animal model development. In this article, we review previous studies in this line of research and emphasize the importance of combining the behavior paradigm of the structured top down attentional modulation of prepulse inhibition with multiple pathogenic factors related to schizophrenia to establish a new model generation, which will be of great significance in investigating both the pathogenesis and the treatment of schizophrenia.

精神分裂症(schizophrenia)是一种病因及发病机制未明的常见重性精神疾病, 部分患者对目前的药物治疗反应差, 病情得不到有效缓解。重复经颅磁刺激（repetive transcrunial magnetic, rTMS）治疗是一种操作简单, 安全无创, 不良反应小的物理治疗方法, 近年来逐渐应用于精神疾病的辅助治疗。既往研究显示rTMS对难治性幻听、阴性症状及认知缺陷可能具有一定疗效。本文简要综述了近年来rTMS治疗精神分裂症的研究进展, 并分析了rTMS可能的治疗机制, 提出白质损伤和神经免疫调节可能是rTMS的治疗机制。

Schizophrenia is a common severe mental disorder, the etiology and pathogenesis of which remains to be elucidated.Some schizophrenia patients respond poorly to the current pharmacological treatments.Repetitive transcranial magnetic stimulation (rTMS) treatment is a simple, safe and non intrusive physical therapy with little side effects, which has been gradually applied as an adjunctive therapeutic technique for schizophrenia.Recent studies indicated that the rTMS treatment has efficacy on medication resistant auditory verbal hallucination, negative symptoms and cognitive deficits.This article will briefly review the recent progress in rTMS treatment of schizophrenia, and summarize its potential therapeutic mechanisms.We suggest that rTMS may target damaged white matter and impaired neuroimmuomodulation.

目的检测孕期氯氮平暴露对子代大鼠学习记忆行为的影响并探讨其机制。方法在妊娠中期（G6-15 d）的大鼠, 每天腹腔注射氯氮平（10 mg/kg）。子代中的雄性成长至8周龄时接受Morris水迷宫试验, 测试其空间学习记忆能力。然后处死动物, 分离出海马和前额叶, 采用Western blot技术检测总MAPK及磷酸化MAPK的水平, 应用RT-PCR技术检测zif268基因表达。结果有孕期氯氮平暴露史的子代大鼠空间记忆的获取、再认、和巩固均较对照表现更好。它们的海马部位MAPK42的磷酸化水平较对照组显著升高,但是其他指标两组间无差别。结论上述结果提示海马组织MAPK42的磷酸化可能在孕期氯氮平暴露导致的子代大鼠空间学习记忆提高中起重要作用。

Objective The aim of this study was to examine the effect of gestational exposure to the antipsychotic clozapine in rats on the spatial learning and memory of adult offspring and to explore the underlying mechanism.Method During the middle period (G6-15) of gestation, pregnant female rats received intraperitoneal injection of clozapine (10 mg/kg) once a day.When growing into 8 week old, the males of the offspring were subjected to Morris water maze test to measure their spatial learning and memory.Their brain tissue was processed for Western blot analysis to assess levels of MAPK44/42 and phosphorylated MAPK44/42, and real time PCR to evaluate the expression of zif 268 gene Result The offspring with the history of prenatal exposure to clozapine showed better performance in the Morris water maze compared with the controls Western blot analysis showed a significant higher level of pMAPK 42 in the hippocampus of rats in the clozapine group, whereas no difference was found between the two groups in terms of the other indices.Conclusion These results suggest an important role of the MAPK42 phosphorylation in the promotion of the spatial learning and memory of adult offspring by clozapine given to pregnant female rats during the middle period of gestation

抑郁症(depression)是一种严重影响人类健康的高发精神疾病, 其发病机制尚不清楚。单胺类神经递质假说是被广泛接受的抑郁症发病的生物学机制之一, 但以此研发的抗抑郁药物存在起效慢、有效率低的缺点。越来越多的证据表明, 炎性反应过程参与抑郁症的发病。目前抑郁症的诊断主要依靠症状学, 因此抑郁症可能是症状相同的一类疾病, 其中存在一种“炎性亚型”, 其特征是患者存在高炎性状态。本文从脑内炎细胞因子、神经胶质细胞及其神经生物学作用与抑郁症的关系综述了抑郁症发病的炎性机制, 探讨抗感染治疗抑郁症的可能性。

Depression is a severe mental disorder with a high prevalence and its pathogenesis is not fully understood Of the proposed hypotheses about depression, monoamine hypothesis is being commonly accepted.The hypothesis driven antidepressants, however, take their effects after a relatively long term, and produce no efficacy in some patients.There is increasing evidence for the involvement of neuroinflammation in the pathogenesis of depression.The diagnosis of depression is mainly based on the clinical manifestations composed of a variety of symptoms, which may be considered as the phenotypes of a class of mental disorders Of the depression patients, some are characterized with high levels of inflammatory factors and can be classified the “inflammatory subtype” of depression.This article reviewed the recent findings of proinflammation cytokines and neuroglia in depression patients and animal models of it, discussed the neurobiological actions of these inflammatory factors in the pathogenesis of depression, and explored the possible anti inflammation strategies for the treatment of depression

随着对哮喘致病机制的深入认识, 近年来提出按照临床、病理、分子生物学特征对哮喘进行更精细划分。当哮喘按照“内型”理论研发的靶向药物在特定类型哮喘患者中取得了很好的疗效后, “同一疗法适合所有患者”的治疗理念正受到挑战。同时也预示了传统的哮喘非特异性治疗（如糖皮质激素、茶碱等为主的基础治疗）模式, 将转向以靶向为主的特异性治疗（如抗IgE, 抗IL 5单抗治疗等）模式。新疗法的研制成功将开辟哮喘治疗的崭新领域。

With deep understanding of pathogenesis in asthma, this disorder with vast heterogeneity should be redefined by clinical, pathologic and molecular biological characteristics.As the target therapy has succeeded in specific subgroup of asthmatics according to “endotype” theory, “one size fits all” approach is facing major challenges.It implies traditional non specific asthma treatment such as corticosteroid, theophylline will turn to target therapy dominated specific treatment such as anti IgE, anti IL-5 antibody et al.These new therapies will open a brand new field for asthma treatment.

研究型企业最重要的责任之一是保护参与临床研究实验和其他研究实验的志愿者的安全。多年来, 这个责任主要是机构审查委员会和伦理委员会负责, 但他们当中的许多机构已经负担过重不能面对日益复杂的全球化研究企业所面临的挑战。2000年, 在一系列美国研究保护措施失败后, 政府和学术界带头人倡导一种系统性、综合性的方法来完成相关保护工作的研究, 他们对人类研究保护项目认证协会在推进新方法同时可能会促进研究保护和研究质量也进行了讨论。人类研究保护项目认证协会（Association for the Accreditation of Human Research Protection Programs, AAHRPP）成立于2001年, 自从它成立后就成了人类研究保护项目的全球领导者, 并一直致力于人类保护研究计划（Human Research Protection Programs, HRPPs）, 提高研究保护水平, 帮助HRPPs在现在以及今后的几年里建立医学伦理研究基金会。

One of the overriding responsibilities of the research enterprise is to protect those who volunteer for clinical trials and other research studies.For years,that responsibility rested primarily with institutional review boards and ethics committees,many of which were overburdened and ill equipped to meet the challenges of an increasingly complex and global research enterprise.In 2000,after a series of U.S.research protection failures,government and academic leaders began advocating for a systemic,integrated approach to research protections—one that begins at the highest level of an organization.These same leaders argued that accreditation could play a key role in advancing this new approach and improving both research protections and quality.The Association for the Accreditation of Human Research Protection Programs（AAHRPP）was founded in 2001 and has since emerged as the global leader in accrediting human research protection programs（HRPPs）.In the process,AAHRPP has been instrumental in achieving acceptance of HRPPs,raising standards for research protections,and helping HRPPs lay the foundation for ethical research today and in the years to come.

国家基因库是服务于国家战略需求的国家级公益性创新科研及产业基础设施建设项目。2011年1月, 国家发展改革委员会正式批复同意依托深圳华大基因研究院组建深圳国家基因库。同年10月国家发展改革委员会、财政部、工业和信息化部、国家卫生计划生育委员会（原卫生部）联合批复同意深圳国家基因库建设方案, 相关项目列入国家战略性新兴产业发展专项资金计划。国家基因库建立集资源样本库、生物信息库、生物资源信息网络为一体的发展及运营模式, 并由深圳华大基因研究院组建及运营, 拟通过建立高水平的生物资源样本库、高效的生物信息数据处理、存储与管理系统以及覆盖广泛的联盟网络, 有效保护、合理开发和利用我国生物资源及基因数据资源, 该项目的建设实施有利于保护我国珍贵且特有的遗传资源, 实现样本资源、基因及数据资源共享开发利用, 提高我国遗传资源样本和基因信息数据的储存、分析、管理和应用能力, 进而推动生命科学和生物产业发展。这对于我们国家抢占未来生物经济的战略制高点、掌控生物遗传资源、基因战略资源, 具有极其重要的战略意义。

China National Genebank Shenzhen（CNGB）is a national nonprofit institute,which is founded to serve the strategic needs of the Chinese government and to boost innovative scientific research and the infrastructure construction for biological industries.In January 2011,CNGB was approved by the National Development and Reform Commission（NDRC）.Later in 2011,the Construction Scheme of CNGB was jointly approved by NDRC,the Ministry of Finance（MOF）,the Ministry of Industry and Technology Information（MIIT）and the National Health and Family Planning Commission（NHFPC,The original Ministry of Health）,funded in the Special Fund Plan for the Development of National Strategic Emerging Industry.CNGB is established and operated by BGI Shenzhen characterizing in a creative development model which combines biological bank,informatics bank and biological resources information consortium network together.With the goal of establishing a world leading biological bank,with highly efficient biological information data processing,storage and management system and comprehensive consortium network,CNGB provides effective protection as well as rational utilization of the Chinese massive bio resources（include both human and non human specimen）and related clinical（or phenotypic）information and OMICS data.The establishment of CNGB is essential for protecting genetic resources in China,for realizing the development and application as well as sharing of sample and data resources.CNGB also strives to improve the capabilities of storing,analyzing,managing and utilizing of specimen and relevant information storage,analysis,management and applications,which will consequently propel the development of biological industry and life science.In summary,CNGB has great strategic significant importance for our country to seize the commanding heights of bio economy,and to possess take control of the strategic biological genetic resources and genetic data.

本文针对自体干细胞治疗下肢缺血目前的现状与未来的发展进行了详细的介绍, 治疗内容包括目前主流的自体骨髓干细胞、自体外周血干细胞和改良的骨髓干细胞, 同时也对我国干细胞治疗政策进行了说明, 并对该领域临床转换的方向提出了自己的看法。

This paper introduced the present situation and development of autologous stem cell therapy about lower limb ischemia,including the current mainstream therapy of autologous bone marrow stem cells,autologous peripheral blood stem cells and improved bone marrow stem cells,also explained the Chinese government’s policies about stem cell treatment,and brought up his own views about the direction of clinical conversion in this field.

人体组织样本库在转化医学研究设计及新技术（“组学”）的应用方面发挥着越来越重要的关键性作用, 以期发现疾病的分子机制, 并将新的生物标志物应用于临床试验。尽管病理学家的首要任务是进行临床病理诊断, 但他们在样本库的运行中同样起到关键的、同时又容易被忽视的作用。除在整个生物样本操作周期中需要兼顾临床病理诊断及选取最佳生物样本外, 病理学家还要为研究提供生物样本特征性信息、进行质量控制、协助研究资源的合理分配, 以及对样本使用的研究者进行相关知识的培训等技术性服务。本文对这些关键的原则问题及一系列针对生物样本的肉眼评估及入库判断的大体病理操作规范进行探讨, 这些操作规范体现了病理学家对于生物样本库建设至关重要的作用。总之, 病理学家可协助样本使用者正确理解生物样本的性质（包括生物样本的形态学特征及使用局限性等）, 使生物样本的使用达到科学最大化。我们相信这些原则的实施将会更加便于病理学家和生物样本库管理者之间的协作, 提高研究者对不可再生的生物样本资源的利用价值, 同时优化临床病理程序中生物样本采集的规范化操作。

Human tissue biobanks have an increasingly important role in transforming medical study designs and is critical for application of a wide range of new technologies（“omics”）to the discovery of molecular patterns of disease and for implementation of novel biomarkers into clinical trials.Although pathologists has patient care as their primary mission in their normal practice of pathology, they do play a vital but often underrecognized role in the operation of these tissue banks.Besides making sure that the timing of all operations is consistent with both the requirements of clinical diagnosis and the optimal preservation of biological products, pathologists are needed to characterize tissues for research, to conduct quality assurance programs, to assist with resource allocation decisions, and to serve an educational role for investigators using the tissues.This article describes these key principles and a set of practice gross pathology guidelines focused on the decision for tissue banking at the time specimens are macroscopically evaluated, where pathologist involvement is crucial to biobank management.In conclusion, pathologists play a critical role in helping biobank users understand the principles of specimen evaluation（histologic and structural composition of tissues, and their limitations）so as to optimize the scientific benefit of the tissues.We believe that appreciation of these principles will facilitate the partnership between surgical pathologists and biobank directors, enhance the value of research on non renewable resources of biological samples, and at the same time, optimize the operational standardization of biological sample collection procedures in clinical pathology.

AIP1(apoptosis signal regulating kinase1 interacting protein 1)是Ras-鸟苷三磷酸酶激活蛋白 (Ras GAP) 家族的新成员。近年来研究表明, AIP1不仅能作为肿瘤抑制基因抑制肿瘤发生发展, 还能通过多种信号通路参与调控心血管系统的炎性反应。本文重点回顾AIP1在血管内皮细胞炎性反应中介导的多种信号通路, 分析AIP1在炎性诱导的新生血管及动脉粥样硬化中的调节作用及机制, 为进一步全面研究AIP1在心血管系统中的调节功能提供参考。

AIP1 is a novel member of the Ras GTPase activating protein family.Recent studies suggest that AIP1 can function as a tumor suppressor in tumor cells, and also acts as a anti inflammatory protein in the cardiovascular system.In this review, we summarize the roles and mechanisms of AIP1 in inflammatory signaling and inflammation induced angiogenesis and atherosclerosis.