富马酸奎硫平与氟哌啶醇对精神分裂症抑郁症状影响的对照研究

目的:对照比较富马酸奎硫平与氟哌啶醇对精神分裂症患者抑郁症状的作用。方法:70例精神分裂症偏执型患者随机分为两组,分别予以富马酸奎硫平及氟哌啶醇治疗4周,于入组前、用药第1、14天及第28天以中文版卡尔加里精神分裂症抑郁量表(CDSS-C)、阳性和阴性症状量表(PANSS)及治疗中出现的症状量表(TESS)进行评定,并体格检查及实验室检查,记录不良事件的发生,以量表分值的变化来判断治疗效果及药物不良反应。结果:①70例患者中有21例患者CDSS-C评分≥6分,抑郁发生率为30%;②富马酸奎硫平组与氟哌啶醇组患者在抑郁症状疗效上差异有统计学意义(有效率分别为90.9%和37.5%,P=0.000),在精神病性症状改善方面无统计学差异(有效率分别为44.4%和54.9%,P=0.481);③氟哌啶醇组药物不良反应严重程度及不良反应所引起的痛苦均要明显高于奎硫平组,且对血泌乳素水平影响较大,多个研究时点TESS评分两组差异均有统计学意义(P=0.000～0.002)。结论:富马酸奎硫平相对于氟哌啶醇对精神分裂症的抑郁症状有较好的疗效和较小的不良反应。     

喹硫平、阿立哌唑治疗急性期精神分裂症患者疗效观察

目的了解新型抗精神病药物喹硫平、阿立哌唑治疗急性期精神分裂症患者的疗效。方法将符合ICD-10诊断标准的精神分裂症患者68例按入院的先后顺序予以喹硫平和阿立哌唑治疗,两组各入组34例,用阳性和阴性症状量表（PANSS）、简明精神病评定量表（BPRS）评定精神症状。用副反应量表（TESS）评定不良反应。结果共完成57例,两组在治疗4周、治疗8周时PANSS总分及其各因子分、BPRS分已明显降低（P=0．000）,两组比较差异无统计学意义（P〉0．05）。喹硫平组的主要不良反应为体重增加10例,嗜睡3例;阿立哌唑组为失眠15例,静坐不能5例。结论喹硫平和阿立哌唑均能改善急性期精神分裂症患者阳性、阴性症状和情感症状及认知缺损,两者疗效相当,两药的主要不良反应有所不同。     

喹硫平和利培酮治疗精神分裂症的对照研究

目的以利培酮为对照,探讨喹硫平治疗精神分裂症的疗效和副作用。方法将60例符合CCMD-3诊断标准的精神分裂症病人随机分为两组,分别给予喹硫平和利培酮治疗8周。于治疗前和治疗后1、2、4、8周末采用阳性症状和阴性症状量表(PANSS)评定临床疗效,副反应量表(TESS)评定副反应。结果治疗8周后,两组疗效近似(P>0.05),喹硫平组和利培酮组的显效率差异无显著性(P>0.05);喹硫平组的副反应发生率低于利培酮组,但差异无显著性(P>0.05)。利培酮组锥体外系副反应和内分泌改变的发生均明显高于喹硫平组(P<0.05)。结论喹硫平对精神分裂症患者的疗效与利培酮相当,副作用较小。     

喹硫平与利培酮治疗老年精神分裂症对照研究

目的探讨喹硫平对老年首发精神分裂症的临床疗效及安全性。方法6例首发老年精神分裂症患者随机分成两组,分别给与喹硫平与利培酮治疗8周,用阳性和阴性症状量表（PANSS）和副反应量表（TESS）评定疗效和不良反应。结果两组疗效相当（P〉0．05）,喹硫平不良反应显著少于利培酮（P〈0．05）。结论喹硫平对老年精神分裂症安全有效。     

喹硫平与利培酮对血清催乳素影响的研究

目的了解喹硫平与利培酮对精神分裂症患者的疗效及对血清催乳素的影响。方法对71例符合CCMD-3诊断标准的精神分裂症患者随机分为喹硫平治疗组（33例）与利培酮治疗组（38例）,观察12周,分别于治疗前及治疗后4周、8周、12周予以阳性症状与阴性症状量表（PANSS）,副反应量表（TESS）及血清催乳素测定。结果喹硫平组和利培酮组疗效差异无显著性,两组治疗后4周、8周及12周PANSS总分及各因子分显著下降（P〈0.01）,利培酮组的不良反应高于喹硫平组,主要表现在肌强直、震颤、泌乳（χ^2=5.69,P〈0.01）及闭经（χ^2=6.74,P〈0.01）等不良反应上,利培酮组治疗后4周、8周及12周血清催乳素明显增加（t=13.48,P〈0.01）,而喹硫平组治疗前后无差异。结论喹硫平与利培酮对精神分裂症均有效,但利培酮不良反应大,明显升高血清催乳素,且有较高高血清催乳素不良反应,而喹硫平对血清催乳素影响较少。     

喹硫平和帕罗西汀单药治疗广泛性焦虑的随机对照研究

目的比较喹硫平单药和帕罗西汀单药治疗广泛性焦虑的疗效及安全性。方法将110例广泛性焦虑障碍患者随机分为喹硫平200mg/d治疗或帕罗西汀20mg/d治疗。疗程6周。用汉密尔顿焦虑量表（HAMA）、临床疗效总评量表严重度（CGI-SI）评定疗效,用副反应量表（TESS）、实验室检查及体重评定安全性。结果喹硫平组55例患者中有51例完成研究,帕罗西汀组55例中53例完成研究。喹硫平组有效率为74.5%,痊愈率为27.3%;帕罗西汀组分别为81.8%、50.9%。两组有效率差异无统计学意义,喹硫平组痊愈率高（χ^2=6.45,P=0.01）。两组HAMA、CGI-SI评分在治疗后均下降;喹硫平组第1周末HAMA总分低于帕罗西汀组;除第1周外,帕罗西汀组量表评分均优于喹硫平组。两组均未发生严重不良事件。喹硫平组嗜睡多见,帕罗西汀组出汗及激越多见;研究结束时,喹硫平组体重增加值高于帕罗西汀组[喹硫平组（M,QR）为1kg（0kg,1kg）,帕罗西汀组为0kg（0kg,1kg）;Z=4.0,P=0.01]。结论喹硫平短期控制广泛性焦虑障碍的症状比帕罗西汀快,但是帕罗西汀6周总体的疗效优于喹硫平。     

心理治疗联合富马酸喹硫平在首发精神分裂症中的应用效果

目的观察心理治疗、富马酸喹硫平联合治疗首发精神分裂症(SP)的效果。方法选取2016年1月～2018年7月我院首发SP患者115例,按随机数字表法分联合组(n=58)、药物组(n=57)。药物组予以富马酸喹硫平治疗,联合组予以行为认知疗法、富马酸喹硫平联合治疗。对比两组不良反应、治疗前及治疗3个月后症状(阳性症状、阴性症状)、认知功能、生活质量。结果治疗3个月后联合组患者阳性量表、阴性量表评分低于药物组(P0.05);治疗3个月后联合组正确应答次数、瞬时记忆评分、正确分类数高于药物组,错误应答次数少于药物组(P0.05);治疗3个月后联合组心理功能、躯体功能、社会功能评分高于药物组(P0.05);联合组头晕、困倦、体位性低血压等不良反应发生率低于药物组(P0.05)。结论富马酸喹硫平联合认知行为疗法能有效减轻首发SP患者的临床症状,恢复其认知功能,改善生活质量,降低不良反应发生率。     

帕罗西汀合并喹硫平或利培酮治疗难治性抑郁的疗效比较

目的探讨喹硫平与利培酮治疗难治性抑郁症的疗效与安全性。方法将69例难治性抑郁症分为喹硫平组（35例），利培酮组（34例），所有患者均服用帕罗西汀，观察6周。于治疗前和治疗1周、2周、4周及6周末采用汉密尔顿抑郁量表（HAMD-17）评定疗效，用副反应量表（TESS）评定不良反应。结果喹硫平组显效率为71％，利培酮组为44％。喹硫平组从第2周末起HAMD分低于利培酮组，差异有统计学意义。喹硫平组不良反应相对少。结论喹硫平合并帕罗西汀治疗不伴精神病性症状的难治性抑郁的疗效好，且起效快，不良反应少。     

喹硫平联合舒必利治疗难治性精神分裂症的效果观察

目的：观察喹硫平联合舒比利对喹硫平治疗无效的难治性精神分裂症的效果。方法从我院筛选出120例喹硫平无效的难治性精神分裂症患者，随机分为2组，一组采用氯氮平治疗，另一组采取舒必利联合喹硫平治疗，治疗12周后应用阳性和阴性综合征量表（PANSS）和其分量表、临床整体印象-严重程度量表（CGI-S）、临床整体印象-改善量表（CGI-I）和副反应量表（TESS）分别评价2组疗效和不良反应。结果2组总体疗效无明显差异（P＞0.05），喹硫平联合舒比利对改善难治性精神分裂症患者代谢功能、阴性症状及安全性方面优于氯氮平（ P＜0.05）。结论对难治性精神分裂症伴代谢障碍或阴性症状较重者，可尝试喹硫平联合舒比利作为初始治疗方案，以减少使用或替代氯氮平，降低氯氮平的致命风险及对代谢功能的影响。     

哌罗匹隆与喹硫平治疗首发精神分裂症的临床研究

目的比较哌罗匹隆与喹硫平治疗首发精神分裂症的疗效及安全性。方法将64例首发精神分裂症患者随机分为哌罗匹隆组(研究组)32例,喹硫平组(对照组)32例,分别给予哌罗匹隆和喹硫平治疗,疗程6周。采用阳性与阴性症状量表(PANSS)评定疗效,治疗时出现的症状量表(TESS)评定不良反应。结果治疗6周后两组PANSS评分较治疗前均有显著下降。哌罗匹隆组显效率为65.6%,有效率为78.1%;喹硫平组显效率为62.5%,有效率为75%,两组间疗效差异无统计学意义(P>0.05),两组间TESS评分差异亦无统计学意义。结论哌罗匹隆治疗首发精神分裂症的疗效及安全性与喹硫平相当。     

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.     

墨蝶呤还原酶基因与精神分裂症相关性的研究进展

墨蝶呤还原酶（SPR）催化四氢生物蝶呤（BH4）从头合成途径的最后一步反应。SPR基因遗传缺陷或突变可导致BH。的合成紊乱,影响单胺类神经递质（如多巴胺、5-羟色胺及谷氨酸等）的合成或释放,进而参与包括精神分裂症在内的多种神经精神系统疾病的发生发展过程。此外,SPR基因敲除小鼠表现出持续增强的自主活动等类精神分裂症症状,说明该基因在精神分裂症的发病中扮演重要的角色。进一步研究SPR基因及其单核苷酸多态性的功能,可为阐明精神分裂症的发病机制提供重要的线索,也为新一代抗精神病药物的研制及开发开拓新的视野。现对SPR基因与精神分裂症的相关研究做一综述。     

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.     

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.     

Wnt信号通路与骨髓间充质干细胞增殖及分化的关系

骨髓间充质干细胞（bonemarrow—derived mesenchymal stem cells,BMSCs）是骨髓中不同于造血干细胞的一类细胞,其来源丰富,取材简便,易分离、纯化、培养,在一定的条件下可以迅速体外扩增,具有多向分化潜能,可以通过不同的方法被诱导分化成骨细胞、软骨细胞、肌细胞、神经胶质细胞、神经元细胞等,而且它具有低免疫源性,向病变部位迁移的能力,     

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。     

癫痫与自杀

自杀而导致死亡被为是增加癫痫患者死亡率的最重要原因之一。国外许多研究报道都表明癫痫患者的自杀率比普通人群的自杀率高几倍到二十几倍。可能导致癫痫患者自杀的危险性因素是有多方面的,本文将从5-HT、抗癫痫药及癫痫手术治疗、精神病理等方面对癫痫患者可能存在自杀危险因素进行综述,并希望在癫痫的综合治疗中对这些危险因素能加以考虑。