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      Meta-Analysis for Clinical Evaluation of Xingnaojing Injection for the Treatment of Cerebral Infarction

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          Abstract

          Objective: Xingnaojing injection (XNJ) is derived from An-Gong-Niu-Huang pill, a well-known traditional Chinese patent medicine, which is widely used for stroke. To evaluate the therapeutic effect of XNJ on cerebral infarction, an extensive meta-analysis was used.

          Methods: Six major electronic databases including the Chinese Biomedical Database (CBM), Wanfang, the VIP medicine information system (VMIS) and the China National Knowledge Infrastructure (CNKI), PubMed, Embase, and the Cochrane Library were examined to retrieve randomized controlled trials designed to evaluate the clinical efficacy of XNJ in treating CI before November 26, 2016.

          Results: There were 53 randomized controlled trials with 4915 participants in this study. The results reflected that compared with the conventional therapy (CT) alone, XNJ could significantly improve the overall response rate ( OR = 3.56, 95% CI [2.94, 4.32], P < 0.00001), and clinical symptom (including increasing activities of daily living (ADL, MD = 10.23, 95% CI [9.47, 10.99], P < 0.00001), and reduce infarction size ( MD = -1.83, 95% CI [-2.49, -1.16], P < 0.00001)). However, there was no significant difference between the XNJ treatment and conventional therapy in Glasgow Coma Scale (GCS, P = 0.32). Neurological deficit score demonstrated that XNJ could significantly reduce the score in two different evaluation criterions as National Institutes of Health Stroke Scale (NIHSS, MD = -3.44, 95% CI [-4.52, -2.36], P < 0.00001), and the Chinese Stroke Scale (CSS, MD = -5.72, 95% CI [-6.94, -4.50], P < 0.00001). Additionally, serum MMPs, including MMP-2 and MMP-9 were significantly reduced by XNJ treatment compared with conventional therapy ( MD = -11.24, 95% CI [-20.83, -1.65], P = 0.02; MD = -25.08, 95% CI [-35.49, -14.67], P < 0.00001, respectively). Moreover, XNJ was able to improve hemorrheology in reducing whole blood viscosity, plasma viscosity, and hematocrit ( MD = -1.44, 95% CI [-2.18, 0.70], P = 0.001; MD = -0.22, 95% CI [-0.37, -0.07], P = 0.003; MD = -3.63, 95% CI [-6.23, -1.03], P = 0.006, respectively). The therapeutic efficacy of XNJ was found associated with improving hemodynamics (increasing peak-flow rate, and average velocity) ( MD = 12.66, 95% CI [10.50, 14.81], P < 0.00001; MD = 9.90, 95% CI [8.63, 11.17], P < 0.00001). XNJ was also related to reducing cholesterol and triglyceride ( MD = -1.06, 95% CI [-1.21, -0.92], P < 0.00001; MD = -1.05, 95% CI [-1.12, -0.97], P < 0.00001).

          Conclusion: Despite the sample size and the poor quality of the included studies of this review, the results of the research showed that XNJ might be a beneficial therapeutic method for the treatment of cerebral infarction.

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          Most cited references71

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          Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling.

          Recent improvements in the monitoring and modelling of stroke have led to more reliable estimates of stroke mortality and burden worldwide. However, little is known about the global distribution of stroke and its relations to the prevalence of cardiovascular disease risk factors and sociodemographic and economic characteristics. National estimates of stroke mortality and burden (measured in disability-adjusted life years [DALYs]) were calculated from monitoring vital statistics, a systematic review of studies that report disease surveillance, and modelling as part of the WHO Global Burden of Disease programme. Similar methods were used to generate standardised measures of the national prevalence of cardiovascular risk factors. Risk factors other than diabetes and disease burden estimates were age-adjusted and sex-adjusted to the WHO standard population. There was a ten-fold difference in rates of stroke mortality and DALY loss between the most-affected and the least-affected countries. Rates of stroke mortality and DALY loss were highest in eastern Europe, north Asia, central Africa, and the south Pacific. National per capita income was the strongest predictor of mortality and DALY loss rates (p<0.0001) even after adjustment for cardiovascular risk factors (p<0.0001). Prevalences of cardiovascular risk factors measured at a national level were generally poor predictors of national stroke mortality rates and burden, although raised mean systolic blood pressure (p=0.028) and low body-mass index (p=0.017) predicted stroke mortality, and greater prevalence of smoking predicted both stroke mortality (p=0.041) and DALY-loss rates (p=0.034). Rates of stroke mortality and burden vary greatly among countries, but low-income countries are the most affected. Current measures of the prevalence of cardiovascular risk factors at the population level poorly predict overall stroke mortality and burden and do not explain the greater burden in low-income countries.
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            Meta-analysis of traditional Chinese patent medicine for ischemic stroke.

            A large number of traditional Chinese patent medicine (TCPM) are widely used for ischemic stroke in China. The aim of this study was to systematically review the existing clinical evidence on TCPM for ischemic stroke. We identified all TCPM that were listed in the Chinese National Essential Drug list of 2004 and those commonly used TCPM in current clinical practice for ischemic stroke. Fifty-nine TCPM were identified for further evaluation. We applied Cochrane systematic review methods. We searched for reports of randomized controlled trials and controlled clinical trials on any of the 59 TCPM for ischemic stroke comparing one TCPM with control. PRIMARY OUTCOMES included death or dependency at the end of follow-up (at least 3 months) and adverse events. Effects on neurological impairments were a secondary outcome. One-hundred ninety-one trials (19,338 patients) on 22 TCPM were available and included, of which 120 were definite or possible randomized controlled trials and 71 were controlled clinical trials. The methodological quality of included trials was generally "poor." Few trials reported methods of randomization. Three trials were randomized, double blind, and placebo-controlled. one trial on Puerarin and one trial on Shenmai injection assessed death or dependency at the end of long-term follow-up (at least 3 months) and found no statistically significant difference between 2 groups. The reported adverse events including allergic reaction, headache, nausea, diarrhea, bellyache, blood pressure change, and subcutaneous ecchymosis. Most of the adverse events were not severe. analysis of the secondary outcome, "marked improvement in neurological deficit," showed apparent benefits of about the same magnitude for all the TCPM studied. Of the 22 TCPM, 8 drugs (Milk vetch, Mailuoning, Ginkgo biloba, Ligustrazine, Danshen agents, Xuesetong, Puerarin, and Acanthopanax) had relatively more studies and patient numbers. There was insufficient good quality evidence on the effects of TCPM in ischemic stroke on the primary outcome (death or dependency). We considered the apparent benefit on neurological impairment was as likely to be attributable to bias from poor methodology as to a real treatment effect. However, because the agents assessed appeared potentially beneficial and nontoxic, further randomized controlled trials are justified. Eight drugs could be further research priorities.
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              Current therapies in ischemic stroke. Part A. Recent developments in acute stroke treatment and in stroke prevention.

              Stroke is the third leading cause of death with an increasing prevalence. In previous years many important achievements and new therapeutic strategies have been established. This article provides an overview on recent developments and is an update to the article of Green et al. that was published in 2004. As this article is a comprehensive review we divided it in two parts. In this Part A of our review, recent developments in acute stroke treatment and in stroke prevention are described. In Part B we will reflect on neuroprotection. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                29 August 2017
                2017
                : 8
                : 485
                Affiliations
                [1] 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine Chengdu, China
                [2] 2Department of Pharmacy, Xindu District Shibantan Public Hospital Chengdu, China
                Author notes

                Edited by: Jean-Paul Deslypere, Proclin Therapeutic Research Pvt. Ltd., Singapore

                Reviewed by: Stefano Giovagnoli, University of Perugia, Italy; Gerfried Karl Hans Nell, NPC Nell Pharma Connect Ltd., Austria

                These authors have contributed equally to this work.

                This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2017.00485
                5583602
                28912713
                90234f9a-c0df-48e8-8087-56be2b51a36b
                Copyright © 2017 Ma, Yang, Chen, Xie, Wang, He and Wang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 March 2017
                : 07 July 2017
                Page count
                Figures: 10, Tables: 1, Equations: 0, References: 75, Pages: 12, Words: 0
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81473371
                Award ID: J1310034
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                xingnaojing injection,cerebral infarction,meta-analysis,systematic review,clinical evaluation

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