503例住院精神分裂症患者共患糖尿病的调查

目的：调查住院精神分裂症患者糖尿病的发生情况及相关因素。方法：对503例住院精神分裂症患者进行病历资料回顾，体格检查及血生化检测。结果：住院精神分裂症患者糖尿病的时点患病率为12．9％，显著高于一般人群的3．21％（OR=4．48，CI=3．43～5．84，P〈0．01）。40—49岁的患者中糖尿病患病率增高明显（14．6％vs．3．02％，OR=5．51，CI=3．49～8．70，P〈0．01）。糖尿病发生与年龄、体质量超重及腹型肥胖有关。糖尿病组患者的病程比非糖尿病患者长（Z=-6．989，P〈0．01），接受目前抗精神病药物治疗时间也比非糖尿病患者长（Z=-4．794，P〈0．01）。氯氮平新发糖尿病患病率高于利培酮组与经典药物组（P〈0．01），利培酮组与经典药物组患病率差异无统计学意义（P〉0．05）。结论：住院精神分裂症患者糖尿病患病率高于一般人群，与患者年龄、体质量超重、病程及抗精神病药治疗时间有关。氯氮平比利培酮及经典药物可能更容易导致糖尿病的发生。     

抗精神病药物与高血糖关系探讨

目的：了解分析目前在我院住院治疗的精神分裂症患者血糖增高情况及其与患者病程，服抗精神病药物等因素关系。方法：调查分析符合CCMD3诊断标准的住院精神分裂症患者中高血糖发生情况，以及分析患者患病病程，糖尿病家族史，抗精神病药物的使用情况等相关因素，并观察患者体重，体重指数，血糖变化。将精神分裂症患者高血糖发生率与脸群患病率进行比较，分析产生高血糖的相关因素。结果：165例精神分裂症住院患者中高血糖发生率16．4％，为普通人群患糖尿病率2．5％的7倍。长期服用抗精神病药物会引起体重、体重指数增加及患者高血糖的发生与病程长短，患者年龄，糖尿病家族史阳性等因素有关。患者的高血糖发生，服非经典与经典抗精神病药物相比较无显著差异。两种以上抗精神病药物联用者高血糖发生率高。结论：精神分裂症患者长期服抗精神病药物引起体重、体重指数增加及其高血糖的发生率远高于一般人群。精神分裂症患者血糖增高可能是长期服抗精神病药物所致的一种延迟性，慢性药物不良反应的表现。应引起临床工作者关注。     

精神分裂症患者伴发代谢综合征的患病率调查

目的调查国内精神分裂症患者中代谢综合征的患病率及分析可能的相关影响因素。方法对住院的精神分裂症患者进行问卷调查和实验室测定，代谢综合征的诊断标准采用2004年中华医学会糖尿病分会代谢综合征标准。结果符合入组条件者共完成602例。精神分裂症患者中代谢综合征患病率为35．5％。与代谢综合征患病风险相关的危险因素包括年龄、性别、抗精神病药物种类及精神分裂症的病程（P〈0．05）。Logistic回归分析结果显示，女性精神分裂症患者罹患代谢综合征的相对危险度明显高于男性。年龄的相对危险度为12．27（95％CI2．238-32．557）。抗精神病药物种类与代谢综合征的患病风险有关（P=0．047〈0．05）。结论与普通人群相比，精神分裂症患者具有较高的代谢综合征发病风险，可能的危险因素包括女性、高龄、病程长及服用氯氮平药物等。     

精神分裂症与糖尿病关系的探讨

目的：了解住院精神分裂症患者中糖尿病的发病情况及其与抗精神病药等因素的关系。方法：回顾性调查符合CCMD－2－R诊断标准的住院精神分裂症患者中的糖尿病发病情况以及抗精神病药的使用情况等相关因素,观察体重、血糖和血脂的变化。糖尿病的诊断按照 WHO关于糖尿病的诊断标准（1980年）作出。将精神分裂症患者中的糖尿病发生率与一般人群中的患病率进行比较,并分析影响糖尿病发生的相关因素。结果：在503例精神分裂症住院患者中,糖尿病的发生率为15．1％,为普通人群（2．5％）的6倍（x^2＝18．10,P＜0．01）。抗精神病药物可引起体重的显著增加(t＝5．45,P＜0．01）。糖尿病的发生与精神分裂症的持续病程、长期住院、患者的年龄以及阳性糖尿病家族史等因素有关。氯氮平对糖尿病的影响与其他抗精神药物无显著差异（x^2＝0．38,P＞0．05）。结论：精神分裂症患者中糖尿病的发生率远高于普通人群,抗精神病药物引起的体重增加可能与此有关,临床上应予以关注。     

氯氮平和经典抗精神病药的长期治疗对患者体重、糖代谢及血脂的影响

目的 探讨长期应用氯氮平和经典类抗精神病药(APS)对精神分裂症患者体重、血糖和血脂等代谢指标的影响及其可能的相关因素.方法 共调查使用APS≥5年的精神分裂症患者271例,分别测量其身高和体重,检测空腹和餐后2h血糖、空腹血清游离脂肪酸、血清胰岛素和瘦素水平.按药物使用情况将患者分为氯氮平组、经典APS单一治疗组(经典组)或联合用药组进行比较.结果 [1]联合用药组体质量指数、空腹血糖、血甘油三酯和血游离脂肪酸水平均显著高于经典组(P＜0.05);血胰岛素和胰岛素抵抗指数也均显著高于经典组和氯氮平组(P＜0.05).[2]氯氮平组和联合用药组糖耐量降低和2型糖尿病发生率均明显高于经典组(P＜0.05).[3]患者体质量指数与其空腹血糖、血清瘦素、血甘油三酯、胆固醇水平以及与胰岛素抵抗指数均呈正相关(P均小于0.05);患者血清瘦素水平与其血胰岛素水平也呈正相关(P=0.008).[4]多元逐步线型回归分析表明,进入影响空腹血糖水平方程的因素分别为胰岛素抵抗指数、血胰岛素、胆固醇和体质量指数(P＜0.05).结论 单用氯氮平及其与经典抗精神病药联用,均易导致患者肥胖,且易导致患者血糖、血脂、血游离脂肪酸水平升高,并与胰岛素抵抗和糖耐量降低发生相关,可能增加2型糖尿病的发生.     

住院精神分裂症患者伴发代谢综合征的临床分析

目的调查住院精神分裂症患者代谢综合征的发生率,分析与代谢综合征有关的危险因素。方法将符合CCMD-3诊断标准的住院精神分裂症患者为研究对象,以2004年中华医学会糖尿病分会代谢综合征为标准,了解精神分裂症患者伴发代谢综合征的发生率,并用Logistic回归分析其相关因素。结果符合入组条件者共726例,精神分裂症患者伴发代谢综合征患病率为32.3%。代谢综合征患病相关的危险因素为年龄、氯氮平及精神分裂症的病程（P〈0.05）。Logistis回归分析结果显示,精神分裂症患者伴发代谢综合征的危险因素是高龄,病程。结论与普通人群相比,精神分裂症患者具有较高伴发代谢综合征患病风险,可能的危险因素为高龄,病程长和服用氯氮平等。     

长期住院精神分裂症患者糖代谢异常分析

目的：调查住院慢性精神分裂症患者合并糖代谢异常情况。方法：自制一般情况调查表，回顾糖尿病病史，检测空腹血糖、餐后2h血糖、血脂，计算体重指数(BMI)。结果：305例住院男性慢性精神分裂症患者中，糖尿病25例(8．2％)，糖代谢异常者111例(36．4％)；高年龄、长病程、肥胖者，糖代谢异常发生率高；糖代谢异常组三酰甘油(TG)、BMI较高；病程、TG、肥胖是糖代谢异常发生的危险因素。结论：慢性精神分裂症患者糖代谢异常发生率高于普通人群，临床上应予以关注。     

长沙地区50岁以上常住居民超重及肥胖的流行病学调查

目的 调查长沙市50岁以上人群超重和肥胖的流行特征,为制定相应的干预措施提供科学依据。方法 采用分层整群随机抽样的方法,以长沙市天心区20个社区作为调查点,对50～90岁常住居民超重和肥胖的相关因素进行调查,并调查不同体质量人群中的高血压分布。结果 该地区人群超重及肥胖患病率分别为38.9%和6.1%,女性超重和肥胖患病率为33.1%和5.3%,男性为46.8%和7.1%,男性明显高于女性（P均＜0.01）。60～69岁人群超重的发生率较50～59岁和70～90岁人群高（P =0.032,0.005）。经多元逐步回归分析发现,年龄、性别、劳动强度、吸烟、饮酒与体质指数（body mass index, BMI）有相关性,高血压的患病率与BMI呈正比。结论 长沙市50岁以上人群超重和肥胖患病率较高,尤其是男性;影响BMI的主要因素有年龄、性别、劳动强度、吸烟和饮酒等;随着BMI增加,高血压患病率增加。     

住院精神分裂症患者脂代谢异常发生率及其相关因素调查

目的对住院精神分裂症患者脂代谢异常发生率及其相关因素进行调查。方法采用自制的调查表对235例住院精神分裂症患者进行调查,分别收集患者的性别、年龄、受教育年限、性格、病程、住院时间、既往病史(高血压、糖尿病)、服用抗精神病药物等相关资料,同时检测体质量、身高、空腹血糖、甘油三酯、总胆固醇、高密度脂蛋白及低密度脂蛋白等相关指标。结果 235例住院精神分裂症患者中,存有脂代谢异常158例,发生率为67.2%。外向、超重、高血压及未服用阿立哌唑患者更易发生脂代谢异常(P0.05)。外向患者总胆固醇及甘油三酯均明显高于内向患者(P0.05)。超重患者甘油三酯明显高于非超重患者(P0.01)。高血压住院精神分裂症患者甘油三酯明显高于非高血压患者(P0.05)。Logistic回归分析显示,外向、超重是脂代谢异常发生的高危因素,服用阿立哌唑是脂代谢异常发生的保护性因素。结论住院精神分裂症患者脂代谢异常发生率较高,外向、超重的患者较易发生脂代谢异常,而服用阿立哌唑可降低脂代谢异常发生的风险。     

精神分裂症并发糖尿病的相关因素分析

目的了解住院精神分裂症患者并发糖尿病的相关因素。方法回顾性调查符合CCMD-3诊断标准的住院精神分裂症患者中的糖尿病发病情况以及抗精神病药物的使用情况等相关因素,并观察体重、血糖和血脂的变化。结果在302例精神分裂症患者并发糖尿病者为39例(12.91%),其发生与患者的年龄、病程、体重、血脂和阳性糖尿病家族史以及使用抗精神病药物有相关性。结论精神分裂症患者中糖尿病的发生率远高于普通人群,年龄较大、病程较长以及抗精神病药物的长期使用均可增加糖尿病的发生率。     

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.     

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.     

雷公藤内酯对癫痫大鼠神经元P13K／Akt／mTOR蛋白的影响

目的通过检测癫痫大鼠海马神经元P13K、Akt和mTOR蛋白表达,探讨雷公藤内酯抑制癫痫大鼠神经元凋亡的分子机制。方法30只大鼠随机分为对照组、海人酸组、雷公藤内酯干预组,免疫组化法检测各组大鼠海马神经元P13K、Akt和mTOR蛋白的表达情况。结果海人酸组神经元胞体皱缩,形态不规则,数量减少,而雷公藤内酯干预组神经元的数量和形态与对照组相似,海人酸组海马神经元P13K、Akt、ITITOR蛋白表达与对照组比较均减少,而雷公藤内酯干预组海马神经元的P13K、Akt、mTOR蛋白表达均较海人酸组增加,差异均有统计学意义（P〈0．05）。结论雷公藤内酯可能通过上调P13K／Akt／mTOR信号通路蛋白表达对癫痫大鼠海马神经元发挥保护作用。     

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.     

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.     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.