神经节苷脂联合甲钴胺注射液治疗糖尿病周围神经病变的疗效

目的观察单唾液酸四己糖神经节苷脂钠(GM1)联合甲钴胺注射液治疗2型糖尿病周围神经病变(DPN)临床疗效。方法将DPN患者60例随机分成2组,均给予甲钴胺注射液500μg肌注,治疗组加用GMI 40mg+生理盐水250mL静滴,1次/d,连用2周,观察2组临床疗效及神经传导速度。结果治疗组临床疗效明显优于对照组(P0.05),神经传导速度增加亦优于对照组(P0.001),治疗过程中未见明显不良反应。结论 GM1联合甲钴胺注射液治疗DPN安全有效。     

甲钴胺联合依帕司他治疗糖尿病周围神经病变临床观察

目的 观察甲钴胺联合依帕司他治疗糖尿病周围神经病变(DPN)的临床疗效.方法 选择住院DPN病人72例,均使用胰岛素控制血糖,随机分为治疗组及对照组各36例,治疗组使用甲钴胺注射液联合依帕司他治疗,对照组肌内注射VitB1及VitB12,疗程均为2周,观察2组治疗前后的变化.结果 甲钴胺联合依帕司他治疗DPN疗效明显优于B族维生素组(P＜0.01).结论 甲钴胺联合依帕司他治疗DPN安全有效.     

川芎嗪联合马来酸桂哌齐特治疗TIA疗效观察

目的观察川芎嗪联合马来酸桂哌齐特治疗短暂性脑缺血发作(TIA)的疗效。方法对55例TIA患者随机分为治疗组30例与对照组25例,2组均给予川芎嗪注射液160mg加5%葡萄糖或生理盐水250mL,静滴,1次/d;治疗组联合应用马来酸桂哌齐特320mg,加5%葡萄糖或生理盐水250mL静滴,1次/d,疗程均为14d。结果治疗组、对照组总有效率分别为93.3%和76.0%,2组比较差异有统计学意义(P<0.05)。结论川芎嗪联合马来酸桂哌齐特治疗TIA疗效显著,值得临床推广。     

马来酸桂哌齐特联合长春西汀治疗急性脑梗死疗效观察

目的观察马来酸桂哌齐特联合长春西汀治疗急性脑梗死的临床疗效及安全性。方法选择临床确诊的急性脑梗死患者76例,随机分成治疗组和观察组各38例。治疗组给予马来酸桂哌齐特注射液320mg,长春西汀30mg,阿司匹林0.1g口服,每晚1次;对照组给予长春西汀30mg,阿司匹林0.1g口服,每晚1次,连用14d。治疗期间采用中国卒中量表（CSS）对神经功能缺损进行评定。结果 治疗组临床总有效率89.5%,对照组为65.8%,治疗组疗效明显优于对照组,2组总有效率比较差异有统计学意义（P〈0.01）。结论 马来酸桂哌齐特联合长春西汀治疗脑梗死疗效显著,能有效改善脑梗死患者神经功能,值得临床进一步推广。     

马来酸桂哌齐特注射液对后循环缺血患者的血液流变学和血流动力学的影响

目的 观察马来酸桂哌齐特对后循环缺血的血液流变学和血流动力学的影响.方法 将104例患者随机分为2组,常规治疗组50例,予拜阿司匹林片100 mg,1次/d;阿托伐他汀钙片20 mg,1次/d;控制血压血糖等.治疗组54例在此基础上加用马来酸桂哌齐特注射液320 mg静滴,1次/d;2组均以治疗前、治疗后2周检测血液流变学、高敏C反应蛋白(hs-CRP)和TCD检查并进行疗效评定.结果 治疗组治疗后血浆黏度、全血黏度和hs-CRP明显降低,TCD检查VA、BA血流好于常规治疗组,总有效率90.7%,优于常规治疗组74.0%,差异有统计学意义.结论 马来酸桂哌齐特能降低血黏度和hs-CRP,改善VA、BA血流,是治疗后循环缺血的有效药物.     

马来酸桂哌齐特注射液治疗糖尿病周围神经病变临床观察

目的观察马来酸桂哌齐特注射液治疗糖尿病周围神经病变(DPN)的临床疗效和安全性。方法选择50例2型糖尿病周围神经病变患者,随机分为观察组和对照组各25例,观察组采用马来酸桂哌齐特注射液治疗,对照组给予红花注射液,比较2组疗效。结果经14d治疗,观察组总有效率96.0%,明显高于对照组的72.0%,差异有统计学意义(P<0.01)。疗程结束后,2组患者正中神经、腓总神经MCV和SCV得到改善(P<0.05),但观察组患者改善幅度更显著(P<0.01)。2组患者治疗前后血糖及肝、肾功能各项指标比较,差异无统计学意义(P>0.05)。结论马来酸桂哌齐特注射液对DPN具有较好的临床疗效,且无明显不良反应,安全性高,值得临床推广应用。     

马来酸桂哌齐特治疗椎基底动脉供血不足疗效观察

目的观察马来酸桂哌齐特治疗椎基底动脉供血不足的疗效。方法将70例椎基底动脉供血不足患者随机分为治疗组(38例)和对照组(32例),治疗组使用马来酸桂哌齐特注射液320mg加入生理盐水250ml中静滴,1次/d,14d为一个疗程;对照组使用丹参粉针400mg加入生理盐水250ml中静滴,1次/d,14d为一个疗程,观察临床疗效。结果治疗组总有效率明显好于对照组,2组差异有显著性(P0.05)。结论马来酸桂哌齐特治疗椎基底动脉供血不足的疗效显著。     

缬沙坦联合甲钴胺治疗糖尿病周围神经病变的临床分析

目的试用血管紧张素受体拮抗剂缬沙坦联合神经修复剂甲钴胺对糖尿病周围神经病变(DPN)患者进行临床治疗研究,并作临床疗效和安全性评价。方法DPN患者126例,随机分为对照组63例和治疗组63例。对照组:控制血糖,肌注甲钴胺针500μg,1次/d,连续12周。治疗组:在对照组基础上加缬沙坦80mg口服,1次/d,共12周。结果治疗前后2组痛觉过敏与感觉减退;尺神经与腓神经的神经传导速度的差异均有统计学意义。结论缬沙坦与甲钴胺合用可明显提高DPN的疗效,是一种新型、高效与安全的治疗方法。     

长春西汀治疗糖尿病周围神经病变疗效观察

目的 观察长春西汀治疗糖尿病周围神经病变(DPN)的临床疗效.方法 将83例DPN患者随机分为观察组42例和对照组41例,2组的基础治疗为:糖尿病饮食、降糖药物及维生素B1 100 mg,甲钴胺500 μg肌内注射,1次/d,观察组加用长春西汀注射液30 mg加入500 ml生理盐水静滴,1次/d.治疗4周后,观察2组疗效.结果 与治疗前相比,观察组周围神经传导速度明显提高,观察组总有效率高于对照组,差异具有统计学意义(P<0.05).结论 长春西汀对糖尿病周围神经病变的临床治疗有积极意义,值得推广应用.     

马来酸桂哌齐特注射液治疗椎基底动脉供血不足疗效观察

目的 观察马来酸桂哌齐特治疗椎基底动脉供血不足的疗效.方法 将94例患者随机分为2组,治疗组48例应用马来酸桂哌齐特320mg加入5%葡萄糖250ml或生理盐水250ml静滴,1次/d,14d为1个疗程.对照组46例,用脉络宁注射液20ml加入盐酸倍他司丁500ml静滴,1次/d,14d为1个疗程.比较2组疗效.结果 治疗组起效快,总有效率95.58%,对照组起效慢,总有效率86.96%,2组比较差异有统计学意义(P<0.01).结论 马来酸桂哌齐特可明显改善脑供血,是治疗椎基底动脉供血不足的有效药物.     

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.     

周围神经松解术在糖尿病足治疗中的应用

目的探讨糖尿病周围神经松解术（decompressionofperipheralnerves,DOP）治疗糖尿病周围神经病（diabeticperipheralneuropathy,DPN）的原理和疗效。方法对DPN患者通过切开韧带或纤维组织松解神经通路上的受压部位,去除神经受压的压迫,改善神经的血供,并使神经可以随邻近关节的运动而滑动。结果实施周围神经松解术可有效帮助DPN患者恢复感觉,缓解疼痛,提高生活质量。结论DOP为DPN的治疗提供了一个新的治疗方法。     

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.     

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。     

Targeting 13-secretase with RNAi in neural stem cells for Alzheimer＇s disease therapy

There are several major pathological changes in Alzheimer＇s disease, including apoptosis of cho- linergic neurons, overactivity or overexpression of 13-site amyloid precursor protein cleaving enzyme 1 （BACE1） and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein （AI3） production, and introduced it into the pSilenCircle vector to construct a short hairpin （shRNA） expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing AI3 protein production. We anticipate that this technique combining cell transplantation and gene ther- apy will open up novel therapeutic avenues for Alzheimer＇s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.     

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.     

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.     

阿尔茨海默病治疗的研究进展

阿尔茨海默病（AD）是一种隐匿性起病,进行性恶化的神经退行性疾病,临床最初表现为认知功能障碍,并有可能在5～10年内完全衰退。患者往往伴随严重的记忆力丧失、精神行为异常、人格改变、言语功能障碍,无法独立生活,最终近乎于植物状态。Ferri等采用DISMOD软件在全球60岁以上人群中估计,全球的痴呆患者人数到2040年将达到8llO万左右。     

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。