Objective:To explore the appropriate modeling method of the early warning model of ischemic stroke recurrence in TCM.Methods:This was a prospective,multi-center and registered study conducted in 7 clinical subcenters ...Objective:To explore the appropriate modeling method of the early warning model of ischemic stroke recurrence in TCM.Methods:This was a prospective,multi-center and registered study conducted in 7 clinical subcenters from 8 provinces and 10 cities in China between 3rd November 2016 and 27th April,2019.1,741 patients with first-ever ischemic stroke were recruited.Univariate analysis was carried out using distance correlation coefficient,mutual information entropy,and statistical correlation test.Multivariate analysis adopted multi-factor Cox regression model and combined with expert opinions in the field of stroke to determine modeling variables.The generalized estimating equation of longitudinal data and the Cox proportional hazard regression model of cross-sectional data were used to construct and compare in the early warning model of ischemic stroke recalls.The area under the ROC curve(AUC value)was used to evaluate the early warning capability of the model.Results:The follow-up time was 1-3 years,and the median follow-up time was 1.42 years(95%CI:1.37-1.47).Recurrence events occurred in 175 cases,and the cumulative recurrence rate was 10.05%(95%CI:8.64%-11.47%).The AUC values of the TCM syndrome and TCM constitution model were 0.71809 and 0.72668 based on the generalized estimating equation and the AUC values.Conclusion:The generalized estimating equation may be more suitable for the construction of early warning models of stroke recurrence with TCM characteristics,which provides a certain reference for the evaluation of secondary prevention of ischemic stroke.展开更多
The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction(XCD)based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion(MCAO) m...The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction(XCD)based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion(MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke(IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis.We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis.Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids(SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.展开更多
Objective:To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China.Methods:A prospective,multicenter and registry study was carried out in 2,558 patients at 7 represent...Objective:To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China.Methods:A prospective,multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3,2016 to February 17,2019.A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors.Additionally,stroke recurrence was defined as a primary outcome indicator.Results:A total of 327(12.78%)patients endured recurrence events,1,681(65.72%)patients were men,and the average age was 63.33±9.45 years.Totally 1,741(68.06%)patients suffered first-ever ischemic stroke,1,772(69.27%)patients reported to have hypertension,and1,640(64.11%)of them reported dyslipidemia,1,595(62.35%)patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment(TOAST)classification.Specifically,1,271(49.69%)patients were considered as qi-deficient constitution,and 1,227(47.97%)patients were determined as stagnant blood constitution.There were 1,303(50.94%)patients diagnosed as blood stasis syndrome,1,280(50.04%)patients exhibited phlegm and dampness syndrome and 1,012(39.56%)patients demonstrated qi deficiency syndrome.And 1,033(40.38%)patients declared intracranial artery stenosis,and 478(18.69%)patients reported carotid artery stenosis.The plaque in 1,508(41.36%)patients were of mixed.Particularly,41.09%of them demonstrated abnormal levels of glycated hemoglobin(HbA1 c)levels.Conclusions:Recurrence in minor and small-artery stroke cannot be ignored.Hypertension,dyslipidemia,abnormal HbA1 c,intracranial artery stenosis and carotid plaque were more common in stroke patients.Particularly,phlegm-dampness and blood stasis syndromes,as well as qi deficiency and blood stasis constitutions,were still the main manifestations of stroke.(Trial registration at ClinicalTrials.gov,No.NCT03174535)展开更多
基金National Key R&D Program of the Ministry of Science and TechnologyConstruction of the Technical System for"Treating the Disease"in Traditional Chinese Medicine(No.2018YFC1704705)2015 Special Research Project of the Chinese Medicine Industry of the National Administration of Traditional Chinese Medicine:R&D and Demonstration of Recurrence Risk Assessment System for Ischemic Stroke Disease with Chinese Medicine Characteristic Health Management(No.201507003-8).
文摘Objective:To explore the appropriate modeling method of the early warning model of ischemic stroke recurrence in TCM.Methods:This was a prospective,multi-center and registered study conducted in 7 clinical subcenters from 8 provinces and 10 cities in China between 3rd November 2016 and 27th April,2019.1,741 patients with first-ever ischemic stroke were recruited.Univariate analysis was carried out using distance correlation coefficient,mutual information entropy,and statistical correlation test.Multivariate analysis adopted multi-factor Cox regression model and combined with expert opinions in the field of stroke to determine modeling variables.The generalized estimating equation of longitudinal data and the Cox proportional hazard regression model of cross-sectional data were used to construct and compare in the early warning model of ischemic stroke recalls.The area under the ROC curve(AUC value)was used to evaluate the early warning capability of the model.Results:The follow-up time was 1-3 years,and the median follow-up time was 1.42 years(95%CI:1.37-1.47).Recurrence events occurred in 175 cases,and the cumulative recurrence rate was 10.05%(95%CI:8.64%-11.47%).The AUC values of the TCM syndrome and TCM constitution model were 0.71809 and 0.72668 based on the generalized estimating equation and the AUC values.Conclusion:The generalized estimating equation may be more suitable for the construction of early warning models of stroke recurrence with TCM characteristics,which provides a certain reference for the evaluation of secondary prevention of ischemic stroke.
基金supported by the National Natural Science Foundation of China(No.81704049)“Young Talents”Project of Dongzhimen Hospital of Beijing University of Chinese Medicine(No.DZMYS-201803)。
文摘The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction(XCD)based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion(MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke(IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis.We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis.Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids(SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.
基金Supported by Traditional Chinese Medicine Research Special Project(No.201507003-8)Construction of a Service System for Traditional Chinese Medicine Preventive Treatment of Disease(No.2018YFC1704705)。
文摘Objective:To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China.Methods:A prospective,multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3,2016 to February 17,2019.A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors.Additionally,stroke recurrence was defined as a primary outcome indicator.Results:A total of 327(12.78%)patients endured recurrence events,1,681(65.72%)patients were men,and the average age was 63.33±9.45 years.Totally 1,741(68.06%)patients suffered first-ever ischemic stroke,1,772(69.27%)patients reported to have hypertension,and1,640(64.11%)of them reported dyslipidemia,1,595(62.35%)patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment(TOAST)classification.Specifically,1,271(49.69%)patients were considered as qi-deficient constitution,and 1,227(47.97%)patients were determined as stagnant blood constitution.There were 1,303(50.94%)patients diagnosed as blood stasis syndrome,1,280(50.04%)patients exhibited phlegm and dampness syndrome and 1,012(39.56%)patients demonstrated qi deficiency syndrome.And 1,033(40.38%)patients declared intracranial artery stenosis,and 478(18.69%)patients reported carotid artery stenosis.The plaque in 1,508(41.36%)patients were of mixed.Particularly,41.09%of them demonstrated abnormal levels of glycated hemoglobin(HbA1 c)levels.Conclusions:Recurrence in minor and small-artery stroke cannot be ignored.Hypertension,dyslipidemia,abnormal HbA1 c,intracranial artery stenosis and carotid plaque were more common in stroke patients.Particularly,phlegm-dampness and blood stasis syndromes,as well as qi deficiency and blood stasis constitutions,were still the main manifestations of stroke.(Trial registration at ClinicalTrials.gov,No.NCT03174535)
