迟发性运动障碍与血清尿酸的关系

目的：观察伴迟发性运动障碍（TD）的精神分裂症患者血清尿酸变化，探索尿酸与TD的关系。方法：采用尿酸酶法测定23例TD患者、相匹配的23例非TD患者及24例正常对照的血清尿酸水平，使用异常不自主运动量表（AIMS）评定TD的严重程度。结果：TD组血清尿酸水平显著低于非TD组及对照组（P均〈0．01），而非TD组与对照组之间血清尿酸水平无差异。TD组中AIMS评分与血清尿酸水平呈负相关（r=-0．435，P〈0．05）。结论：TD患者存在低血清尿酸水平并与TD的严重程度有关，尿酸可能参与了TD的病理生理过程。     

利培酮和喹硫平对女性精神分裂症患者催乳素影响的两年随访研究

目的 探讨长期使用利培酮对女性精神分裂症患者的催乳素水平的影响.方法 120例女性精神分裂症患者被随机分为利培酮组和喹硫平组进行2年的随访研究.于治疗前,治疗后2月、12月及24月分别测其催乳素水平进行比较.血清催乳素浓度使用放免法进行测定.结果 喹硫平组与治疗前相比差异无显著性而利培酮组与治疗前相比明显增加,差异有显著性,但随疗程的增加差异逐渐缩小,两组间治疗各时点PRL浓度比较有显著性差异;利培酮组治疗前与治疗后的PRL差值与BPRS减分率显示无相关性.患者PRL水平与利培酮及喹硫平剂量无明显相关性.结论 利培酮治疗女性精神分裂症患者初期血清催乳素水平显著升高,但随着治疗时间的延长,血清PRL水平会逐步降低;PRL水平的变化与疗效及利培酮的剂量无相关性.     

精神分裂症伴发迟发性运动障碍的血清S100B蛋白浓度研究

目的 比较伴发和未伴发迟发性运动障碍(tardive dyskinesia,TD)的慢性精神分裂症患者血清S100B蛋白的浓度,探索S100B蛋白在TD发生中的作用.方法 采用酶联免疫吸附法检测95例伴发TD(TD组,n ＝ 40)与未伴发TD(非TD组,n ＝ 55)的慢性精神分裂症患者和40名正常对照的血清S100B蛋白浓度,比较3组间的差异;采用阳性和阴性症状量表(positive and negative syndrome scale,PANSS)评定精神病理症状,采用异常不自主运动量表(abnormal involuntary movement scale,AIMS)评定TD严重程度,分析血清S100B蛋白浓度与精神病理症状、TD严重程度的关系.结果 TD组、非TD组和对照组的血清S100B蛋白浓度分别为(0.17 ± 0.04)μg/L、(0.15 ± 0.02)μg/L和(0.10 ± 0.03)μg/L,3组的差异有统计学意义(F ＝ 53.07,P ＜ 0.01),前两者均明显高于对照组(P ＜ 0.01),且TD组高于非TD组(P ＜ 0.01).TD组血清S100B蛋白浓度与AIMS总分正相关(r ＝ 0.52,P ＜ 0.01).结论 TD患者血清S100B蛋白浓度较非TD患者还高,而且与TD严重程度正相关,提示胶质细胞功能异常可能在TD发生、发展过程中可能起一定作用.     

精神分裂症迟发性运动障碍患者血清脑源性神经营养因子水平研究

目的 通过比较迟发性运动障碍(TD)、非TD精神分裂症患者(TD-)和正常对照人群血清脑源性神经营养因子(BDNF)水平,探索外周BDNF浓度与TD的关系。方法 运用酶联免疫吸附法(EISIA),检测104例TD、46例TD-患者和44名正常人血清BDNF、浓度,选取46例一般状况与TD-组匹配的TD患者与TD-、正常对照组血清BDNF水平进行比较;对104例TD患者血清BDNF浓度与异常不自主运动量表(AIMS)各项分值之和进行线性回归分析。结果 46例TD和TD-患者血清BDNF水平与正常对照组比较,有显著性差异(P<0.05);TD与TD-组间无显著差异(P>0.05)。104例TD患者血清BDNF水平与AIMS各项分值之和的相关系数为0.359,相关系数显著性检验,P<0.001。结论 慢性精神分裂症患者外周BDNF浓度下降,伴发TD的患者异常运动严重程度与BDNF水平显著相关。     

齐拉西酮与阿立哌唑对血清催乳素及体重的影响

目的 探讨精神分裂症患者应用齐拉西酮与阿立哌唑治疗前后对血清催乳素（PRL）及体重的影响.方法 对60例未曾治疗或停药3个月的精神分裂症患者随机给予齐拉西酮与阿立哌唑规范治疗,于治疗前及治疗第8周末用化学发光法测查患者PRL水平并监测体重,进行对比分析.结果 服用齐拉西酮、阿立哌唑患者治疗前后血清催乳素及体重无明显变化（P＞0.05）;同组间比较,治疗前后血清催乳素及体重亦无显著差异（P＞0.05）,性别对血清催乳素无明显影响（P＞0.05）.结论 齐拉西酮与阿立哌唑对患者血清催乳素及体重无升高作用,是较安全的新型抗精神病药物.     

帕利哌酮与利培酮对精神分裂症首次发病患者血清催乳素水平及体质量影响的对照研究

目的：探讨帕利哌酮与利培酮对精神分裂症首次发病患者血清催乳素水平（ PRL）及体质量的影响。方法：130例首发精神分裂症患者随机分成帕利哌酮组66例（实际完成31例）和利培酮组64例（实际完成42例）,分别给予帕利哌酮和利培酮治疗,观察12周。采用阳性与阴性症状量表（ PAN-SS）在治疗前后进行测评;同时检测血清PRL及体质量,比较治疗前后的变化。结果：两组PANSS总分治疗后各周期均显著下降（P均<0.01）,而血清PRL和体质量均较治疗前明显增加（P<0.05）;两组间比较,差异无统计学意义。结论：帕利哌酮与利培酮治疗精神分裂症首次发病患者疗效相当,但两药均可致血清PRL及体质量增高。     

迟发性运动障碍患者超氧化物歧化酶、ATP酶活性改变

目的探讨抗精神病药所致迟发性运动障碍（TD）患者体内自由基代谢状况与TD的关系。方法测定36例TD、36例非TD慢性精神分裂症患者及40名正常人血浆超氧化物歧化酶（SOD）、红细胞ATP酶及丙二醛（MDA）浓度,并进行三组间方差分析;生化指标与异常不自主运动量表（AIMS）总分间的相关性采用直线相关分析。结果对照组血清SOD活性、ATP酶活性均高于TD组及非TD组,对照组MDA浓度低于TD组及非TD组,差异均有统计学意义（均P〈0.05）,TD患者血清SOD活性、ATP酶活性、MDA浓度与非TD组间的差异均有统计学意义（均P〈0.05）。AIMS总分与SOD、ATP酶、MDA均有显著相关（r=-0.225,r=0.225,均P〈0.05）。结论TD患者的血清抗氧化酶、ATP酶活性、脂质过氧化物异常,自由基代谢障碍可能与TD关系密切。     

伴迟发性运动障碍的慢性精神分裂症患者临床特征分析

目的 探讨伴迟发性运动障碍(tardive dyskinesia,TD)的慢性精神分裂症患者的临床特征.方法 采用异常不自主运动评定量表(AIMS)对126例伴TD的慢性精神分裂症患者的不自主运动进行评定,运用阳性和阴性综合征量表(PANSS)对精神症状进行评估,并与1 16例不伴TD的慢性精神分裂症患者相对照.结果 与非TD患者相比较,TD患者相对年龄更大、病程更长(P＜0.01),具有更高的PANSS总分、阴性症状评分及一般病理评分(P＜0.01或P＜0.05).TD严重程度与年龄、性别、总病程、吸烟、临床精神病理无显著相关性(P＞0.05).结论 伴TD与不伴TD的慢性精神分裂症患者有不一样的临床特征,伴TD的患者年龄更大,病程更长,具有更严重的临床精神病理.     

氟哌啶醇、利培酮及齐拉西酮对精神分裂症患者血清催乳素及认知功能影响的对照研究

目的 探讨氟哌啶醇、利培酮及齐拉西酮对精神分裂症患者血清催乳素及认知功能的影响.方法 选取精神分裂症患者120例,随机分为3组,分别予以氟哌啶醇、利培酮、齐拉西酮进行干预治疗.于治疗前及治疗后第4、8、12周末分别进行阳性和阴性综合征量表（PANSS）、精神分裂症认知功能评定量表（SCoRS）评定,并测定血清催乳素（PRL）水平.结果 （1）3组PANSS评分治疗后各时点均较治疗前下降（P＜0.01）.（2）3组患者各时点男性PRL水平均较治疗前升高（P＜0.01）,治疗后12周末齐拉西酮组PRL水平低于利培酮组（P＜0.05）;女性患者中氟哌啶醇组从第8周始、利培酮组从第4周始,PRL水平均较治疗前升高（P＜0.05）,治疗后第12周末齐拉西酮组PRL水平均低于氟哌啶醇组与利培酮组（P＜0.05）.（3）3组患者治疗后各时点SCoRS评分较治疗前下降（P＜0.01）,治疗后各时点SCoRS评分齐拉西酮组低于氟哌啶醇组（P＜0.05,P＜0.01）.结论 氟哌啶醇、利培酮、齐拉西酮均可造成催乳素水平增高.齐拉西酮影响相对较小,对女性患者催乳素水平影响更小.利培酮、齐拉西酮对患者认知功能改善显著优于氟哌啶醇.     

COMT基因多态性与迟发性运动障碍的关联研究

目的探讨中国汉族人口中儿茶酚胺氧位甲基转移酶(COMT)基因Val108/158Met多态性与迟发性运动障碍(TD)的关系。方法以124例伴TD的精神分裂症患者(TD组)、112例不伴TD的精神分裂症患者(非TD组)及112例正常健康对照者(正常对照组)为研究对象,并采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测COMT基因多态性。结果(1)TD组与非TD组及正常对照组比较,等位基因及基因型频率均无统计学差异。(2)非TD组与正常对照组比较,非TD组的高活性G等位基因频率(0.78)显著高于正常对照组(0.70),低活性A等位基因频率(0.22)显著低于正常对照组(0.30);非TD组低活性A/A基因型频率(0.02)显著低于正常对照组(0.07)。(3)COMT基因型与TD严重程度具有显著相关性,A/A基因型患者的TD严重程度评分显著高于G/G基因型。结论本研究未发现COMT基因与TD的发生有关联。不伴TD的精神分裂症可能与COMT基因存在相关性,高活性G等位基因可能增加了不伴TD的精神分裂症的发生风险。COMT基因型与TD严重程度可能具有相关性,低活性A/A基因型患者可能较高活性G/G基因型患者表现更严重的TD。     

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.     

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.     

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。     

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.     

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。     

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.     

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.