中枢神经纳米载药系统的研究进展

许多亲水性的药物,如一些抗生素、抗肿瘤药物和神经肽类在全身性给药后不能透过血脑屏障（BBB）。药物修饰、渗透性方式打开脑毛细血管内皮和选择性的给药方式（颅内给药）都是常用的提高药物进人中枢神经系统（CNS）的方法。而通过纳米载药系统,包括脂质体、固态多聚体纳米颗粒或者固体脂质纳米颗粒等,不仅可以帮助药物透过BBB,同时可以控制药物释放,延缓药物的化学及酶类降解速度。同时纳米载药系统可以降低药物对外周组织的毒性,在提高药物靶向性方面具有非常广阔的应用前景。本文简要介绍了CNS纳米载药系统的研究进展及临床应用状况。     

血脑屏障的组成及跨越血脑屏障策略的研究

随着人口老龄化进程的加剧,全球患有中枢神经系统(central nervous system,CNS)疾病的人数与日俱增。研发新的能够在脑区达到有效治疗浓度的药物是国内外学者研究的热点。而CNS类药物的研发所面临的一个重要难题就是如何使药物透过血脑屏障(blood-brain barrier,BBB),达到有效的治疗浓度。所以认识BBB的生理结构、分子组成,讨论可行的药物跨越BBB的策略,对实现CNS疾病的靶向性、高效性药物治疗具有十分重要的意义。     

腺相关病毒在中枢神经系统的转导与表达特性

正腺相关病毒(adeno-associated virus,AAV)由于自身独特的安全、高效、靶向性且可持续表达等优势在中枢神经系统(central nervous system,CNS)疾病治疗的应用上备受瞩目,本文主要讨论注射途径及时期、病毒类型、受体分布、启动子类型等对AAVs在CNS转导效率与表达的影响,安全性和免疫问题,旨在为AAV介导的中枢神经系统疾病的治疗提供较优的     

乳酸-羟基乙酸共聚物缓释微球的制备工艺与生物学性能

摘要：微球(microspheres)是一种生物物理靶向载药制剂,粒径为1~300 μm。微球的载体材料按其来源可分为天然高分子材料、半合成高分子材料及合成高分子材料。在合成高分子材料中,通过采用合适的制备工艺和处方,制得的载药微球可在几周或几个月时间内以一定速率释放药物,减少给药次数,增加患者顺应性。对蛋白和多肽类药物,微球是相当理想的载药系统。微球制剂是近年来缓释剂型的研究热点,根据临床需要很多药物正被研究成微球制剂。乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]有着优良的安全性、生物相容性和可变的生物降解性,是制备微球的常用基本材料。PLGA缓释微球制剂的制备方法基本上可分为3种：溶剂挥发法、喷雾干燥法、相分离法。溶剂挥发法是常用的制备方法之一,目前PLGA微球作为多肽、蛋白类药物的载体已广泛应用于免疫学、基因治疗、肿瘤治疗、骨缺损修复、眼科等众多医学领域中。 关键词：乳酸-羟基乙酸共聚物;缓释微球;制备;性能     

多肽及蛋白类药物微囊制剂研究的特点*★

学术背景：多肽及蛋白类药物稳定性差、易被酶降解，口服给药的生物利用低，如将其包埋成微囊制剂，不仅能有效防止药物在体内很快被降解，还能够提高药物的稳定性，实现缓释或控释。 目的：介绍几种常用的多肽及蛋白类药物微囊制备方法，并比较各种方法的优缺点，以及常用的药用辅料。 检索策略：由第一、二作者应用计算机检索Proquest 和 Elsevier 数据库1993-01/2008-01文献，检索词为“microcapsule”，限定语言种类为“English”；同时检索维普中文期刊数据库、万方数据库1996-01/2008-01文献，检索词为“微囊”，限定语言种类为中文。纳入与多肽及蛋白类药物微囊制备方法、工艺优化及壁材选择有关文献，排除较陈旧的文献及重复研究。 文献评价：共收集到140篇相关文献，30篇符合标准，其中22篇介绍多肽及蛋白类药物微囊制备方法，8篇关于常用的药用辅料。 资料综合：①多肽及蛋白类药物微囊化的常用制备方法主要有复相乳液法、超临界流体法、喷雾干燥法，具体制备过程中应根据药物的理化性质选择合适的方法。②用于制备多肽或蛋白类药物的壁材主要有可生物降解聚合物和生物黏附材料。 结论：多肽及蛋白类药物微囊制备应根据其不同的理化性质选择合适的制备方法和壁材，以获得最理想的实验结果。同时，多肽及蛋白质类药物的稳定性将是制备过程中需要重点考察的内容。     

经血脑屏障载药纳米材料的研究

血脑屏障的存在使许多药物难以进入中枢神经系统发挥药效.纳米粒子作为一种新型载体,能携载药物穿越血脑屏障而进入脑内,提高脑内药物浓度,是具有脑靶向给药功能的良好载体.近年来国内外学者对脑靶向给药的纳米载体材料(如壳聚糖、脂质体、聚氰基丙烯酸烷酯、聚乳酸等)进行了一系列的研究,并在动物实验获得满意的效果.     

整合素αvβ3受体靶向载药脂质体的制备及体外靶向性

摘要 背景：含RGD序列的多肽是多种整合素的识别位点,以其相对分子质量小、稳定、易于制备,且无免疫原性等优点被广泛用于纳米靶向药物传递系统的设计。 目的：制备以RGD环五肽为配基的整合素αvβ3载药脂质体,通过体外细胞学实验证实其受体靶向性。 方法：使用人工合成的RGD环五肽作为靶向分子探针,通过高压均质法制备靶向整合素αvβ3载药脂质体,采用扫描电镜和激光粒度分析仪检测纳米颗粒形态和粒径;以流式细胞分析观察其对血管平滑肌细胞的特异性标记,并考察荷载药物的离体缓释能力以及体外靶向能力。 结果与结论：合成的靶向载药脂质体粒径为(175±6) nm,包封率为(96.33±1.02)%,体外溶出时间超过5 d。靶向载药脂质体对整合素αvβ3具有较高的特异性亲和力,可通过受体介导的内吞作用进入细胞内。提示制备的靶向整合素αvβ3载药脂质体,具有较高的药物包封率及缓释性,能与整合素αvβ3受体特异性结合,是一种新型的受体介导靶向制剂。 关键词：整合素αvβ3;RGD(精氨酸-甘氨酸-天冬氨酸); 醋酸地塞米松;靶向载药脂质体;生物材料与药物控释 doi:10.3969/j.issn.1673-8225.2010.47.015     

神经干细胞移植治疗中枢神经系统疾病的研究进展

近年来,建立和应用可移植、能克隆、稳定的多潜能神经干细胞(NSC),为细胞移植和基因转移治疗中枢神经系统(CNS)疾病提供了使用方便、特性明确、来源安全的移植材料和运载工具.由于其独特的生物学特性及分离、培养、扩增技术的成熟,NSC被用于治疗CNS损伤和疾病的研究,以促进疾病模型CNS的解剖学和行为学的恢复.下面就NSC移植治疗CNS疾病的研究进展作一综述.     

SUMO化在中枢神经系统疾病中的作用机制研究进展

<正>小泛素化修饰蛋白(small ubiquitin-related modifier,SUMO)是一类高度保守的由97个氨基酸残基组成的多肽,分为SUMO1、SUMO2、SUMO3和SUMO4,参与蛋白质翻译后修饰。SUMO修饰蛋白质的过程称为SUMO化修饰(SUMOylation),SUMOylation参与调节细胞分化、细胞周期、核转录、蛋白间的相互作用、DNA修复等多种病理生理过程~([1])。目前研究表明SUMO化与心脏病、癌症、CNS疾病的发生密切相     

壳聚糖微粒载蛋白质药物：黏膜传输蛋白质及抗体的明星材料

背景：载蛋白质、肽类药物及靶向传输是药物载体研究的热点与难点,壳聚糖作为一种天然阳离子聚合物,生物降解性、相容性、力学性能俱佳,是生物大分子及活性物质的最佳载体材料之一。 目的：分析壳聚糖在蛋白质载体领域的优势,综述壳聚糖及其衍生物在载蛋白质及肽类药物方面的研究成果。 方法：检索中国知网、elsevier、willey等中外文全文数据库有关壳聚糖载蛋白质药物、释药及微粒制剂的内容,检索时间为2005/2010,英文检索词为“chitosan/chitin,microspheres,biomaterial,biopolymer,drug carrier,drug delivery,cell adhesion,ECM,peptide,chemical modification,bioactivity,protein drug,gene delivery,micro-and nanoparticles”;中文检索词为“甲壳素/壳聚糖,微球/微粒/微囊,载体,生物大分子,基因治疗,蛋白质药物,细胞外基质,生物活性,生物相容性,生物降解”。 结果与结论：蛋白质及肽类药物具有疗效好、剂量小、毒副作用小的显著优势,但蛋白质稳定性差、难吸收、体内生物半衰期短的缺点是此类药物使用的巨大障碍。聚合物载药的研究虽多见报道,但在传输蛋白质、肽类药物方面依然面临诸多困难。壳聚糖及壳聚糖衍生物因其卓越的促进吸附性能称为黏膜传输蛋白质及抗体的明星材料,但在制剂的稳定性及定量精确释放等方面仍存在很多挑战。     

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     

帕金森病运动症状进展分析

目的分析帕金森病(PD)患者运动症状进展特点。方法采用PD统一评分量表(UPDRS)Ⅲ对912例PD患者进行评估。结果与病程1年的患者比较,除病程1~2年的患者外,其他病程患者的UPDRSⅢ评分、强直分、姿势或步态异常分、轴性症状总分、言语分、步态分显著升高(均P0.05),病程5~6年及14年患者的震颤分,病程5~6年、7~8年、9~13年、14年患者的运动迟缓分、姿势分显著升高(P0.05~0.01)。轴性症状进展速度高于UPDRSⅢ评分。结论 PD患者病程早期UPDRSⅢ评分进展快,震颤症状进展独立于其他症状,轴性症状评分较UPDRSⅢ更敏感地反映疾病加重趋势。     

Frequency of accumulation of filaments in adaxonal cytoplasm of Schwann cells of myelinated fibers of rat spinal roots

Summary The frequency of accumulation of 6-nm filaments in the adaxonal cytoplasm of Schwann cells in the 6th lumbar dorsal and ventral roots was evaluated in 4-, 8-, 26- and 45-week-old Sprague-Dawley rats. The frequency was higher in 4- and 8-week-old (growing) rats than in 26- and 45-week old (mature) rats, and also higher in ventral than in dorsal roots in 4-, 8- and 26-week old rats. There were no clusters on certain groups of myelinated fibers according to the size of transverse axonal area, in both the ventral and dorsal roots. Therefore, this accumulation may reflect certain functions of the adaxonal cytoplasm of Schwann cell during natural growth and maturation of the axon and myelin sheath.     

Function of circle of Willis

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress.     

Effects of prevention of afferentation of the development of the chick optic lobe

BONDY, S. C., M. E. HARRINGTON AND C. L. ANDERSON. Effects of prevention of afferentation on the developmentof the chick optic lobe. BRAIN RES. BULL. 3(5) 411–413, 1978.—The effects of unilateral extirpation of the right optic cup of the three-day incubated chick embryo upon the rate of synthesis and the stability of DNA in the non-innervated optic lobe, have been studied. This surgical procedure prevents innervation of the optic lobe contralateral to the removed eye, while the other optic lobe is normally innervated by retinal ganglion cells of the remaining eye. At the 20th day of incubation, the DNA content of the non-innervated lobe was below that of the paired lobe receiving normal innervation. This deficiency of cell number was caused by two events; death of an excess number of neurons formed early in embryogenesis and a reduced rate of glial proliferation in the later stages of incubation.     

Modelling of movement of the lamprey: Control of oscillators

This article discusses the control methods of the central pattern generator (CPG). First a control model of the CPG is presented using 2 oscillators, and we suggest that phasic modulation to the CPG by means of phasic information is effective for controlling the phase difference between oscillators. Next, two models for controlling the CPG of a lamprey are proposed. One model describes a control system from the brain stem, in which the reticulospinal neurons control the CPG by receiving feedback signals and sending control signals to the neck region of the CPG. The other is a model for learning an localized control system to generate a desired motor pattern. By means of these models, a role of the efference copy is suggested.     

利培酮对精神分裂症患者生活质量的影响

目的：比较利培酮与氟哌啶醇对精神分裂症患者生活质量的影响。方法：对门诊72例服用氟哌啶醇及74例服用利培酮的精神分裂症患者用生活质量综合评定问卷（GQOLI）、阳性与阴性症状量表（PANSS）、副反应量表（TESS）进行评定。结果：利培酮组患者治疗后生活质量有所提高,而氟哌啶醇组患者生活质量有所下降。结论：利培酮治疗有利于患者提高生活质量。     

腺垂体功能减退症临床特征变化分析

目的探讨腺垂体功能减退症患者的病因结构变化及临床表现。方法回顾性分析我院2013-01—2016-12住院及门诊78例腺垂体功能减退症患者的临床资料。结果男32例(41.03%),女46例(58.97%);诊断时年龄11~89岁,平均62.5岁;鞍区占位(包括术前及术后)52例(66.67%),席汉综合征8例(10.26%),空泡蝶鞍9例(11.65%),病因不明8例(10.26%),垂体-下丘脑发育不良1例(1.28%)。首次就诊科室:纳差厌食、恶心呕吐就诊于消化内科36例(46.15%)最常见。ACTH+TSH+Gn+G激素缺乏为19例最多,占24.36%,ACTH+TSH+Gn缺乏15例,占19.23%。结论腺垂体功能减退症病因结构发生变化,发病人群、首发症状及受累激素也不同,患者女性多于男性,发病年龄偏高,症状不典型,分布于临床多个科室,其中以低钠血症为首发临床表现就诊消化内科最多。     

Standards of instrumentation of EMG

Standardization of Electromyography (EMG) instrumentation is of particular importance to ensure high quality recordings. This consensus report on “Standards of Instrumentation of EMG” is an update and extension of the earlier IFCN Guidelines published in 1999. First, a panel of experts in different fields from different geographical distributions was invited to submit a section on their particular interest and expertise. Then, the merged document was circulated for comments and edits until a consensus emerged.The first sections in this document cover technical aspects such as instrumentation, EMG hardware and software including amplifiers and filters, digital signal analysis and instrumentation settings. Other sections cover the topics such as temporary storage, trigger and delay line, averaging, electrode types, stimulation techniques for optimal and standardised EMG examinations, and the artefacts electromyographers may face and safety rules they should follow. Finally, storage of data and databases, report generators and external communication are summarized.     

《绵阳市社会心理服务工作管理办法》解读

2018年,国家卫生健康委员会等10部委联合发布《关于印发全国社会心理服务体系建设试点工作方案的通知》,四川省绵阳市被列为全国第一批试点地区。绵阳市人民政府依据《中华人民共和国精神卫生法》等相关法律法规和文件精神,结合前期调查研究和社会心理服务工作的试点实际,编制出台了《绵阳市社会心理服务工作管理办法》,并于2021年12月25日起施行。本文围绕社会心理服务的相关概念、办法总则、重点内容、保障措施等方面进行解读,以期为社会心理服务工作的规范、持续和有效开展提供参考。