阿尔采末病发病机制研究进展新视点

阿尔采末病的发病机制一直是神经科学领域未解的难题.近年来最新研究发现tao蛋白过度磷酸化导致神经纤维缠结、轴浆运输障碍、同型半胱氨酸的非血管作用、免疫学机制等导致神经元损伤和凋亡,最终引起阿尔采末发病.     

干眼病发病机制的研究进展

干眼病发病机制复杂,任何原因引起的泪液质和量或动力学异常,最终都会引起泪膜的不稳定,导致眼表组织病变.该文从免疫因素、性激素水平及细胞因子三方面来综述干眼病的发病机制.     

天然多酚类成分缓解高尿酸血症及其机制研究进展

高尿酸血症(hyperuricemia, HUA)是一种机体中嘌呤类物质代谢紊乱导致血清中尿酸水平升高的一种代谢性疾病,严重者可导致痛风。HUA的发病机制主要包括酶活失调、尿酸转运体表达失衡、糖代谢及脂代谢紊乱、肠道稳态失衡等。许多研究报道了天然多酚对高尿酸血症和痛风具有良好的缓解作用。本文对HUA的发病机制和多酚类成分的降尿酸作用及其机制进行了总结与归纳,以期为降尿酸药物的研究与开发提供理论依据。     

中药治疗高血压的研究进展

高血压是当今社会最常见的心血管疾病,研究表明高血压与冠心病、脑卒中、心力衰竭和肾功能障碍密切相关,是导致多种心血管疾病的主要危险因素之一。笔者通过对高血压病的发病机制进行分析,总结了常见的降压中药及其作用机制。     

人体肝脾血吸虫病的发病机制及其防治研究进展

研究了血吸虫对人体肝脾所致损伤的机理、多因素的发病机制、肝脾硬化导致的循环障碍、矸脾功能代偿失调、肝脾血吸虫病的诊断、预后及其防治难点。     

EGb761抑制β—淀粉样蛋白25—35片段诱导的神经元凋亡

以β-淀粉样蛋白25-35片段（β-Amyloid Peptide25-35,β-AP25-35）诱发原代培养小鼠皮层神经元出现凋亡作为阿尔采末症（Alzheimer‘s Disease,AD)的离体模型,在此基础上观察了银杏叶提取物（Extract of leaves of Ginkgo biloba L.,EGb761）及其主要活性成分内酯B（Ginkgolide B,Gin B)对上述神经元损伤的对抗作用。结果表明,EGb761能抑制β-AP25-35引起的神经元活性的下降和超微结构的改变,即抑制β-AP25-35诱导的神经元调亡,从而为EGb761临床用于防治AD提供了实验依据。     

TNF-α在肝衰竭发病中的作用

德国科学家认为 ,肿瘤坏死因子α( TNF-α)及其受体系统对肝发育至关重要。如果抗凋亡级联导致Rel A核因子κB激活无效 ,而导致肝细胞凋亡。研究结果显示 ,TNF-α/TNF- R1系统涉及人类 FHF发病机制。动物模型研究提示 ,Fas相关死亡域可作为分子靶防止肝细胞死亡。TNF-α在肝衰竭发病中的作用     

激素性脱发分子机制的研究进展

雄激素性脱发是男性最常见的脱发类型,但发病机制尚不完全清楚,治疗方法有限。虽然被认为是一种轻微的皮肤病,但它会影响自我形象,导致患者出现心理问题,而且常见的治疗方案也可能导致诸如性欲降低、勃起功能障碍和皮肤过敏等症状。通过对雄激素性脱发的分子机制研究,探寻一种有效、副作用小的药物十分必要,本文就相关研究作一综述。     

少肌性肥胖发病机制和诊断标准的研究进展

随着人口老龄化社会问题的加剧,少肌性肥胖(Sarcopenic Obesity,SO)所带来的各种健康问题已经引起了广泛的关注.但因SO的发病机制尚未完全确定以及诊断标准的不统一,导致SO的流行程度以及SO与健康结果之间的关联不一致.文章对SO的发病机制及其诊断标准的研究进展进行综述,以期对SO的早期诊断、评估和干预有所帮助.     

胰岛素原转化酶基因克隆及序列测定

目的研究胰岛素抵抗和胰岛素缺乏与Ⅱ型糖尿病发病机制的关系.方法Ⅱ型糖尿病普遍存在胰岛素、胰岛素原障碍,胰岛β细胞分泌出胰岛素原经胰岛素原转化酶(Prohormone convertase,PC2)去除部分肽段后形成胰岛素.结果与结论若PC降解功能异常可导致胰岛素原及其代谢产物不适当分泌引起胰岛素缺乏,研究该基因分布和表达的变化,对探讨糖尿病胰岛素抵抗的发病机制奠定基础.     

Temporal and spatial variations in the Palmer Drought Severity Index over the past four centuries in arid, semiarid, and semihumid East Asia

Based on a database of 106 annually resolved tree-ring chronologies and 244 Palmer Drought Severity Index(PDSI)grid data,we attempted to reconstruct gridded spatial drought patterns in each year over the past four centuries in the arid,semiarid,and semihumid East Asia.The results showed that these regions mainly experienced drought events during the periods from AD 1601 to AD 1652,AD 1680 to AD 1718,AD 1779 to AD 1791,AD 1807 to AD 1824,AD 1846 to AD 1885,and AD 1961 to AD 1999.In the middle of the 16th century,severe droughts occurred mainly in North China;during the period from AD 1876 to AD 1878,droughts occurred in most parts of northern China;and from the 1920s to 1940s,catastrophic drought events spread across almost all of northern China and Mongolia.These historical drought events caused severe ecological and environmental problems and substantially affected the development of human society.In these regions,temperature and summer monsoon precipitation are the main factors influencing drought events.In western areas,PDSI and temperature exhibit a close relationship,whereas in eastern areas,summer monsoon rainfall is the dominant factor influencing variations in PDSI.     

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.

A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene.     

沼气厌氧消化过程影响因素研究进展

沼气厌氧消化过程涉及复杂微生物群落在厌氧环境下的协同作用,此过程中的因素变化会导致菌群结构发生改变,进而影响发酵系统的稳定性和效率。本文对影响厌氧发酵过程稳定和效率的因素进行了探讨,包括发酵温度、pH值、碳氮比、有机负荷、停留时间及营养元素等。认为厌氧发酵过程采用混合原料可以弥补单一原料发酵过程的养分不足和特定成分积累对发酵过程稳定性的影响;在发酵温度的选择上,要充分考虑能源输入/输出比,才能保证过程的经济性。     

What can false memory tell us about memory impairments in Alzheimer’s disease?

The range of memory impairments associated with Alzheimer’s disease (AD) has been a focus for psychological and clinical re-searchers for many years. In addition to investigations of AD patients’ veridical memory using traditional recognition memory tasks, a number of recent studies have focused on false memories to reveal the underlying causes of memory impairment in AD. Studies comparing illusory memories between AD patients and healthy older people have revealed various differences in memory deficits between the development of AD and the typical aging processes. Here, we review 3 types of memory illusions tested in AD patients: associative memory illusions, fluency-based false memories and source memory errors. By comparing AD patients with healthy older adults, we sought to analyze the mechanisms underlying AD-related memory impairments at different stages of memory processing, including encoding, retrieval and monitoring. This comparison revealed that AD patients exhibit an impaired ability to establish and utilize gist representations at the encoding stage and impairments in processing on the basis of familiarity and recollection at the retrieval stage. Consequently, patients with AD have access to less information when making memory judgments. As a result, they become more susceptible to the effects of item fluency, which can be manipulated during the retrieval stage. Furthermore, with impaired source memory monitoring abilities, the capacity of AD patients to suppress memory illusions is compromised. Based on these findings, we propose that the study of false memories constitute a critical tool for elucidating the memory impairments involved in AD. Further explorations of these memory impairments will have practical significance for the diagnosis and treatment of AD in the future.     

东海内陆架泥质沉积Rb和Sr的地球化学及其古气候意义

通过对位于东海内陆架闽浙沿岸泥质沉积区北部的DD2孔进行AMS14C年龄测试和Rb,Sr含量测定,获得了近2ka的Rb/Sr比值(RRb/Sr)变化的高分辨率曲线。该曲线揭示出10次RRb/Sr低值时期,它们与历史时期中国温度下降有很好的对应关系,并印证了约990AD的降温事件。根据RRb/Sr的变化,基本认同竺可桢所界定的隋唐温暖期,并认为气候存在温暖-寒冷-温暖的波动,且其中的相对寒冷期为800-890AD。研究认为小冰期时间段为1480-1890AD,且由3个寒冷阶段构成,小冰期的最冷峰为约1520AD,1670AD,1780AD和1850AD。     

证病结合的异常黑胆质型阿尔茨海默病(AD)模型的建立及行为学改变

 在前期已建立的异常黑胆质载体动物模型的基础上,采用聚集态Aβ1-40 双海马定向注射制备证病结合的异常黑胆质型阿尔茨海默病(AD)模型,并以Morris 水迷宫及跳台实验验证证病结合模型的行为学改变特点。结果表明,各组大鼠饮食、水量及体重变化:单纯(AD)组、异常黑胆质证组饮食、水量较正常对照组增加(P<0.05);证病结合的异常黑胆质型AD 模型组饮食、水量较异常黑胆质组减少(P<0.01);单纯AD 组、异常黑胆质证组、证病结合组体重较正常对照组均减轻(P<0.01)。各组大鼠Morris 水迷宫空间探索试验经过有效区域次数:与正常对照组比较,单纯AD 组、异常黑胆质证组、证病结合组经过有效区域次数均减少(P<0.01);与单纯AD 组相比,证病结合组经过有效区域次数明显减少(P<0.05)。各组大鼠跳台测试:与空白对照组比较,单纯AD 组、异常黑胆质证组和证病结合组反应期延长,潜伏期缩短,错误次数增多,学习记忆成绩明显降低(P<0.01);证病结合组与单纯痴呆组相比略低,但无统计学差异(P>0.05)。由此得出,在异常黑胆质载体大鼠模型的基础上,采用聚集态Aβ1-40 双海马定向注射制备证病结合的异常黑胆质型AD 模型,不仅动物体表特征的变化符合维医体液证候改变特点,通过行为学验证后学习记忆改变特点又符合西医疾病的特点。     

阿尔茨海默病致病基因突变相关的啮齿类动物和非人灵长类动物模型

摘要: 我国现有阿尔茨海默病( AD) 患者800 － 1000 万,患者数量随着人口老龄化逐年增加,目前尚无有效治疗或者逆转AD 的药物和方法。过去基于啮齿类动物模型筛选出的用于治疗AD 的药物在人体试验中均疗效差或有严重的副作用,这与啮齿类动物模型和AD 患者病理及行为特征差异大有直接关系。非人灵长类动物与人的大脑和神经系统高度相似,建立AD 非人灵长类动物模型意义重大。AD 病因复杂,但是致病基因突变是其已知的明确病因,应该重视利用基因修饰或者基因筛选等技术建立AD 非人灵长类动物模型。本文将着重介绍AD 致病基因突变相关的转基因小鼠模型和非人灵长类动物模型的特点和现状。     

阿尔茨海默症发病机制及治疗方法研究进展

 阿尔茨海默症（Alzheimer's disease,AD）是以β淀粉样蛋白斑块及神经元纤维缠结为主要病理特征的神经退行性疾病,是痴呆中最常见的一种,也是一种常见的老年人疾病。AD的发病机制可能由多种发病因素、多种通路和分子机制的相互参与引起。由于AD的发病主要同老年人有关,故研究治疗AD的方法对于提高人类健康和生活水平至关重要。虽然目前并没有一种治疗方法可以完全治愈AD,但有多种治疗策略。本文对AD的发病机制及治疗方法的研究进展进行简要综述。     

阿尔茨海默病伴发视觉障碍研究进展

 阿尔茨海默病（AD）是老年人群常见的神经变性疾病,多以记忆力损害为首发症状,逐渐出现进行性认知功能受损和精神行为症状,对家庭和社会带来沉重的经济和照护负担。AD早期症状不明显,待诊断明确后的治疗效果差,因此,早期诊断尤为重要。研究发现,AD患者可出现视觉障碍,但尚无流行病学数据。目前AD的治疗包括非药物及药物等综合手段,AD伴发视觉障碍的治疗尚需研究。本文主要介绍AD视觉障碍的临床症状、发生机制、检测及评价手段,包括光学相干体层扫描、视觉诱发电位、视网膜微血管检查及神经影像学,以对AD患者的视觉障碍进行全面评价,寻找特异、敏感及简便的AD评估手段,为AD的早期诊断及早期干预提供依据。     

Development in the research of molecular mechanism of Alzheimer’s disease

Alzheimer's disease (AD) is a kind of central nervous system disease. The cause of AD is unclear. It is found that the remarkable histopathological characters of AD are senile plaques and neurofibrillary tangles. β-amyloid plays an important role in the formation of senile plaques and the abnormal phosphorylation of Tau protein is the main reason of neurofibrillary tangles. Apolipoprotein E is correlated to AD' s access, and the third pathological character-AMY plaque perhaps represents a new cause of AD. Presenlin and proteinaceous infectious particles are also related with AD. A summary of molecular mechanism for AD and the development of research is presented.