目的系统评价奥氮平对比利培酮治疗阿尔茨海默病精神行为症状的有效性和安全性,旨在为临床合理用药提供循证参考。方法计算机检索PubMed、Embase、Cochrane library、中国知网、万方数据库、维普数据库和中国生物医学文献数据库,收集各...目的系统评价奥氮平对比利培酮治疗阿尔茨海默病精神行为症状的有效性和安全性,旨在为临床合理用药提供循证参考。方法计算机检索PubMed、Embase、Cochrane library、中国知网、万方数据库、维普数据库和中国生物医学文献数据库,收集各数据库自建库至2020年8月发表的奥氮平(试验组)对比利培酮(对照组)治疗阿尔茨海默病精神行为症状的随机对照试验(RCT)。筛选文献,提取数据,使用Cochrane系统评价员手册偏倚风险评估工具进行文献质量评价,采用Rev Man 5.3软件进行meta分析。结果共纳入13项RCT,共计1448例患者。meta分析结果显示,试验组总有效率[RR=1.14,95%CI(1.06,1.23),P=0.0008]显著高于对照组,治疗2周后[WMD=-2.67,95%CI(-3.79,-1.55),P<0.00001]、4周后[WMD=-2.83,95%CI(-4.02,-1.65),P<0.00001]的试验组阿尔茨海默病病理行为评定量表评分均显著低于对照组;两组治疗8周后的阿尔茨海默病病理行为评定量表评分[WMD=-1.40,95%CI(-4.34,1.54),P=0.35]及简易智力状态检查量表评分[WMD=1.01,95%CI(-1.73,3.76),P=0.47]比较,差异无统计学意义。试验组锥体外系反应发生率[RR=0.52,95%CI(0.34,0.80),P=0.003]、失眠发生率[RR=0.49,95%CI(0.32,0.76),P=0.002]均显著低于对照组,两组头痛、乏力、视物模糊、激惹、肝功能、体质量增加、嗜睡发生率比较,差异均无统计学意义(P>0.05)。结论奥氮平治疗阿尔茨海默病精神行为症状的效果优于利培酮,锥体外系反应和失眠发生率低于利培酮。展开更多
OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circu...OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease(AD).METHODS:The mice were allocated into the following nine groups:(a)the C57 Black(C57BL)sham-operated group(control group),(b)ischaemic treatment in C57BL mice(the C57 ischaemic group),(c)the APP/PS1 sham surgery group(APP/PS1 model group),(d)ischaemic treatment in APP/PS1 mice(APP/PS1 ischaemic group),(e)C57BL mice treated with aspirin following ischaemic treatment(C57BL ischaemic+aspirin group),(f)C57BL mice treated with SLT following ischaemic treatment(C57BL ischaemic+SLT group),(g)APP/PS1 mice treated with SLT(APP/PS1+SLT group),(h)APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment(APP/PS1 ischaemic+donepezil hydrochloride group)and(i)APP/PS1 mice treated with SLT following ischaemic treatment(APP/PS1 ischaemic+SLT group).The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism.The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice.The hippocampus of each mouse was observed by haematoxylin and eosin(HE)and Congo red staining.The ultrastructure of NVUs in each group was observed by electron microscopy,and various biochemical indicators were detected by enzymelinked immunosorbent assay(ELISA).The protein expression level was detected by Western blot.The mRNA expression was detected by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS:The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice,which were restored by SLT.The results of HE staining showed that SLT restored the pathological changes of the NVUs.The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex and hippocampus of the APP/PS1 and APP/PS1 ischaemic mice.Furthermore,SLT significantly reduced the content of Aβ,improved the vascular endothelium and repaired the mitochondrial structures.The ELISA detection,western blot detection and qRT-PCR showed that SLT significantly increased the vascular endothelial growth factor(VEGF),angiopoietin and basic fibroblast growth factor,as well as the levels of gene and protein expression of low-density lipoprotein receptor-related protein-1(LRP-1)and VEGF in brain tissue.CONCLUSIONS:By increasing the expression of VEGF,SLT can promote vascular proliferation,up-regulate the expression of LRP-1,promote the clearance of Aβand improve the cognitive impairment of APP/PS1 mice.These results confirm that SLT can improve AD by promoting vascular proliferation and Aβclearance to protect the function of NVUs.展开更多
OBJECTIVE:To analyze the current status of clinical trial registration of Traditional Chinese Medicine(TCM)for the treatment of neurological diseases.METHODS:Interventional clinical trials of TCM treatment for ischemi...OBJECTIVE:To analyze the current status of clinical trial registration of Traditional Chinese Medicine(TCM)for the treatment of neurological diseases.METHODS:Interventional clinical trials of TCM treatment for ischemic stroke,hemorrhagic stroke,vascular cognitive impairment,tension-type headache before September 22,2020 on the platform of Chinese Clinical Trial Registry(Chi CTR),and Clinical Trials.gov were searched.Two researchers independently selected the literature and extracted data.RESULTS:A total of 180 interventional clinical trials were included for analysis.Out of 180 trials,127 were from Chi CTR and 53 from Clinical Trials.gov.The countries primary sponsoring the included trials were China(176,97.8%),and the common categories of primary sponsors were hospital(131,72.8%).Among the study design,the largest proportion of allocation was randomized(172,95.6%),interventional model assignment was parallel(163,90.6%),masking was double blind 49(27.2%),and the sample size was≤400(144,80.0%).The trials were most carried out at a single center(102,56.7%).Among the included studies,112(62.2%)registered on Chi CTR attached the ethical approval documents.In terms of trial stages,50(27.7%)studies were in phaseⅣ.The mostly used intervention was Chinese herbal medicines(99,55%),acupuncture(68,37.8%)was the second.By searching the registration number on China National Knowledge Infrastructure Database and Pub Med,38(21.1%)registered trials were published,including 25 protocol studies and 14 research results with one(NCT02275949)published both the protocol and the results.CONCLUSIONS:Irregular and inadequate reporting,untimely update and publication,insufficient information on traditional medicine unique characteristics,and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological diseases.More efforts need to be made from the above aspects to standardize and improve the registration of traditional medicine trials.展开更多
文摘目的系统评价奥氮平对比利培酮治疗阿尔茨海默病精神行为症状的有效性和安全性,旨在为临床合理用药提供循证参考。方法计算机检索PubMed、Embase、Cochrane library、中国知网、万方数据库、维普数据库和中国生物医学文献数据库,收集各数据库自建库至2020年8月发表的奥氮平(试验组)对比利培酮(对照组)治疗阿尔茨海默病精神行为症状的随机对照试验(RCT)。筛选文献,提取数据,使用Cochrane系统评价员手册偏倚风险评估工具进行文献质量评价,采用Rev Man 5.3软件进行meta分析。结果共纳入13项RCT,共计1448例患者。meta分析结果显示,试验组总有效率[RR=1.14,95%CI(1.06,1.23),P=0.0008]显著高于对照组,治疗2周后[WMD=-2.67,95%CI(-3.79,-1.55),P<0.00001]、4周后[WMD=-2.83,95%CI(-4.02,-1.65),P<0.00001]的试验组阿尔茨海默病病理行为评定量表评分均显著低于对照组;两组治疗8周后的阿尔茨海默病病理行为评定量表评分[WMD=-1.40,95%CI(-4.34,1.54),P=0.35]及简易智力状态检查量表评分[WMD=1.01,95%CI(-1.73,3.76),P=0.47]比较,差异无统计学意义。试验组锥体外系反应发生率[RR=0.52,95%CI(0.34,0.80),P=0.003]、失眠发生率[RR=0.49,95%CI(0.32,0.76),P=0.002]均显著低于对照组,两组头痛、乏力、视物模糊、激惹、肝功能、体质量增加、嗜睡发生率比较,差异均无统计学意义(P>0.05)。结论奥氮平治疗阿尔茨海默病精神行为症状的效果优于利培酮,锥体外系反应和失眠发生率低于利培酮。
基金National Natural Science Foundation of China(81503450):Experimental study on the treatment of transgenic mice with Alzheimer's disease by protecting neurovascular unit by supplementing Qi and activating blood circulation investigate。
文摘OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease(AD).METHODS:The mice were allocated into the following nine groups:(a)the C57 Black(C57BL)sham-operated group(control group),(b)ischaemic treatment in C57BL mice(the C57 ischaemic group),(c)the APP/PS1 sham surgery group(APP/PS1 model group),(d)ischaemic treatment in APP/PS1 mice(APP/PS1 ischaemic group),(e)C57BL mice treated with aspirin following ischaemic treatment(C57BL ischaemic+aspirin group),(f)C57BL mice treated with SLT following ischaemic treatment(C57BL ischaemic+SLT group),(g)APP/PS1 mice treated with SLT(APP/PS1+SLT group),(h)APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment(APP/PS1 ischaemic+donepezil hydrochloride group)and(i)APP/PS1 mice treated with SLT following ischaemic treatment(APP/PS1 ischaemic+SLT group).The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism.The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice.The hippocampus of each mouse was observed by haematoxylin and eosin(HE)and Congo red staining.The ultrastructure of NVUs in each group was observed by electron microscopy,and various biochemical indicators were detected by enzymelinked immunosorbent assay(ELISA).The protein expression level was detected by Western blot.The mRNA expression was detected by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS:The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice,which were restored by SLT.The results of HE staining showed that SLT restored the pathological changes of the NVUs.The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex and hippocampus of the APP/PS1 and APP/PS1 ischaemic mice.Furthermore,SLT significantly reduced the content of Aβ,improved the vascular endothelium and repaired the mitochondrial structures.The ELISA detection,western blot detection and qRT-PCR showed that SLT significantly increased the vascular endothelial growth factor(VEGF),angiopoietin and basic fibroblast growth factor,as well as the levels of gene and protein expression of low-density lipoprotein receptor-related protein-1(LRP-1)and VEGF in brain tissue.CONCLUSIONS:By increasing the expression of VEGF,SLT can promote vascular proliferation,up-regulate the expression of LRP-1,promote the clearance of Aβand improve the cognitive impairment of APP/PS1 mice.These results confirm that SLT can improve AD by promoting vascular proliferation and Aβclearance to protect the function of NVUs.
基金Supported by NATCM TCM Inheritance and Innovation Hundred-Thousand-Ten Thousand“Talents Project Qi Huang Scholar)-National TCM Leading Personnel Support Program(NATCM Personnel and Education Department[2018]No.12)”Research on optimizing construction of evidence-based ability of traditional Chinese medicine encephalopathy(No.ZZ13-024-3),Special fund for basic scientific research business expenses of central public welfare scientific research institutes。
文摘OBJECTIVE:To analyze the current status of clinical trial registration of Traditional Chinese Medicine(TCM)for the treatment of neurological diseases.METHODS:Interventional clinical trials of TCM treatment for ischemic stroke,hemorrhagic stroke,vascular cognitive impairment,tension-type headache before September 22,2020 on the platform of Chinese Clinical Trial Registry(Chi CTR),and Clinical Trials.gov were searched.Two researchers independently selected the literature and extracted data.RESULTS:A total of 180 interventional clinical trials were included for analysis.Out of 180 trials,127 were from Chi CTR and 53 from Clinical Trials.gov.The countries primary sponsoring the included trials were China(176,97.8%),and the common categories of primary sponsors were hospital(131,72.8%).Among the study design,the largest proportion of allocation was randomized(172,95.6%),interventional model assignment was parallel(163,90.6%),masking was double blind 49(27.2%),and the sample size was≤400(144,80.0%).The trials were most carried out at a single center(102,56.7%).Among the included studies,112(62.2%)registered on Chi CTR attached the ethical approval documents.In terms of trial stages,50(27.7%)studies were in phaseⅣ.The mostly used intervention was Chinese herbal medicines(99,55%),acupuncture(68,37.8%)was the second.By searching the registration number on China National Knowledge Infrastructure Database and Pub Med,38(21.1%)registered trials were published,including 25 protocol studies and 14 research results with one(NCT02275949)published both the protocol and the results.CONCLUSIONS:Irregular and inadequate reporting,untimely update and publication,insufficient information on traditional medicine unique characteristics,and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological diseases.More efforts need to be made from the above aspects to standardize and improve the registration of traditional medicine trials.
