Potential Therapeutic Activity of Berberine in Thyroid-Associated Ophthalmopathy: Inhibitory Effects on Tissue Remodeling in Orbital Fibroblasts.

Purpose: Berberine (BBR), an alkaloid produced by a traditional Chinese plant, was recently attributed multiple effects on lipometabolism, inflammation, and fibrosis. Thyroid-associated ophthalmopathy (TAO) is highly associated with these pathologic changes. Thus, we aimed to examine the potential therapeutic effect of BBR in an in vitro model of TAO. Methods: Orbital fibroblasts (OFs) obtained from control donors (n = 6) or patients with TAO (n = 6) were cultured. The CCK-8 assay was conducted for assessing the optimal concentration range. Oil Red O staining, Western blotting, and quantitative RT-PCR (qRT-PCR) were conducted to assess adipogenesis in OFs. RNA sequencing (RNA-seq) was used to screen the key pathways of the antiadipogenic effect mediated by BBR. Along with incremental concentrations of BBR, IL-1ß-induced expression of proinflammatory molecules was determined by ELISA and qRT-PCR. In addition, TGF-ß-induced hyaluronan (HA) production and fibrosis were evaluated by ELISA, qRT-PCR, and Western blotting. Results: TAO-OFs, but not control fibroblasts (CON-OFs), were readily differentiated into adipocytes with the commercial medium. Intracellular lipid accumulation was dose-dependently decreased by BBR, and adipogenic markers were also downregulated. Moreover, the PPARγ and AMPK pathways were screened out by RNA-seq and their downstream effectors were suppressed by BBR. Besides, BBR attenuated IL-1ß-induced expression of proinflammatory molecules in both TAO-OFs and CON-OFs by blocking nuclear factor-κB signaling. BBR's inhibitory effect on TGF-ß-mediated tissue remodeling was also confirmed in OFs. Conclusions: These findings demonstrate BBR has outstanding capabilities of controlling adipogenesis, inflammation, HA production, and fibrosis in OFs, highlighting its potential therapeutic role in TAO management.

Clinical effectiveness of Qilong capsule in patients with ischemic stroke: A prospective, multicenter, non-randomized controlled trial.

BACKGROUND: The Qilong capsule (QLC) is a Chinese patented medicine characterized by an equal emphasis on replenishing Qi and activating blood circulation. In 2000, China's FDA approved the use of QLC for ischemic stroke (IS). However, there is not yet much high-quality evidence of the clinical effectiveness of QLC combined with conventional treatment (CT) for IS with Qi deficiency and blood stasis syndrome. PURPOSE: In this study, we conducted a prospective, multicenter, non-randomized controlled trial at 7 hospitals in China to investigate the clinical effectiveness of QLC combined with CT for IS with Qi deficiency and blood stasis syndrome. METHODS: Participants aged 35 to 80 years old diagnosed as IS with Qi deficiency and blood stasis syndrome in TCM were recruited. Participants were treated with QLC (intervention group) or non-QLC (control group). The intervention course of QLC was 12 weeks. All participants in two groups received standard treatment. All participants returned for in-person follow-up visits at the 12th week and 24th week. Primary outcome measures included a modified Rankin Scale (mRS), the National Institute of Health Stroke Scale (NIHSS), and the Barthel Index (BI). Secondary outcome measures included TCM syndromes (Qi deficiency syndrome score, blood stasis syndrome score), psychological index (self-rating depression scale, SDS; self-rating anxiety scale, SAS), blood lipid index, blood coagulation index, homocysteine, and favorable functional outcome (mRS 0 - 3). Multiple imputations were used for any missing data. Propensity score matching (PSM) was used to deal with any confounding factors (age, gender, scale score, etc.). Rank alignment transformation variance analysis (ART ANOVA) and generalized linear mixed model (GLMM) were introduced to improve the scientific and accuracy of repeated measurement data. All statistical calculations were carried out with R 3.6.1 statistical analysis software. RESULTS: A total of 2468 participants were screened from November 2016 to January 2019. Finally, 2302 eligible participants were included in the analysis. There were 1260 participants in the intervention group (QLC group) and 1042 participants in the control group (non-QLC group). After PSM matching, sub-samples of 300 participants in the QLC group and 300 participants in the non-QLC group were finally formed. The final results of clinical effectiveness are the same results shared by the total samples and sub-samples after PSM. In the 24th week after treatment, QLC combined with CT proved to be significantly better than CT alone in reducing the scores of mRS (p < 0.05), NIHSS (p < 0.001), Qi deficiency syndrome (p < 0.01), and blood stasis syndrome (p < 0.001), SAS (p < 0.05), as well as in improving BI score (p < 0.05). The favourable functional outcome (mRS score of 0 to 3 at week 12) was statistically different between QLC and non-QLC group in the sub-samples (p < 0.01, 97% vs 91.7%). The results of the ART ANOVA showed that the improvement of mRS (p < 0.01), BI (p < 0.05) and NIHSS (p < 0.001) in QLC group was better than non-QLC group when the interaction effect was considered. The results of GLMM showed that the reduction of mRS and NIHSS scores of patients in the QLC group were better than those of the non-QLC group (p < 0.001). The BI score of the QLC group in the sub-samples after PSM increased more than the non-QLC group (p < 0.001). There was no evidence showing that QLC can cause serious adverse reactions (ADRs) in treating patients with IS. CONCLUSION: QLC combined with CT was better than CT alone in reducing mRS score, NIHSS score, Qi deficiency syndrome score, blood stasis syndrome score, and SAS score, as well as improving BI score after treatment. Further high-quality RCTs are needed to confirm the positive results. The study protocol was embedded in a registry study that registered in the Clinical Trials USA Registry (registration No. NCT03174535).

Onset and Recurrence Characteristics of Chinese Patients with Noncardiogenic Ischemic Stroke in Chinese Medicine Hospital.

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%) 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, and 1,640 (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 levels. CONCLUSIONS: Recurrence in minor and small-artery stroke cannot be ignored. Hypertension, dyslipidemia, abnormal HbA1c, 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).

[Pharmacoeconomic evaluation of Qidong Yixin Oral Liquid in treatment of viral myocarditis (Qi-Yin deficiency syndrome) with TreeAge Pro].

To evaluate the pharmacoeconomic value of Qidong Yixin Oral Liquid in the treatment of viral myocarditis(Qi-Yin deficiency syndrome) by supplementing Qi, nourishing the heart, calming the mind, and relieving palpitation, the present study performed the Meta-analysis based on the published papers on Qidong Yixin Oral Liquid by AMSTAR and carried out pharmacoeconomic evaluation using TreeAge Pro by the cost-effectiveness analysis. The results showed that the quality of the included papers was good. After four weeks of treatment, Qidong Yixin Oral Liquid combined with the conventional treatment regimen was superior to the conventional treatment in improving creatine kinase isoenzyme, and the difference was statistically significant. Furthermore, the treatment cost was also higher than that of conventional treatment, with an incremental cost-effectiveness ratio of CNY 95.89, accounting for 0.30% of per capita disposable income. The results of sensitivity analysis showed that the research results were robust. Therefore, based on the assumption that the per capita disposable income in 2020 was the threshold of patients' willingness to pay, it is more economical for patients with viral myocarditis to use Qidong Yixin Oral Liquid combined with conventional secondary prevention regimen than conventio-nal secondary prevention regimen alone. The economic evaluation of Qidong Yixin Oral Liquid in the treatment of viral myocarditis will help physicians and patients choose optimal treatment options, improve rational clinical medication, and provide references for the efficient allocation and utilization of medical resources in China.

A tumor microenvironment responsive nanoplatform with oxidative stress amplification for effective MRI-based visual tumor ferroptosis.

As a promising new form of non-apoptotic regulated cell death, ferroptosis has potential as an effective supplement to apoptosis-based cancer treatments. However, high intracellular glutathione (GSH) levels and insufficient hydrogen peroxide (H2O2) in the tumor limit the efficacy of ferroptosis. Here, we designed a theranostic nanoplatform, named FCS/GCS, by incorporating amphiphilic polymer skeletal (P-SS-D), cinnamaldehyde prodrug (CA-OH) and iron ions (Fe3+)/gadolinium ions (Gd3+) via chelation reactions between Fe3+/Gd3+ and polyphenols. When delivered in the tumor microenvironment with high GSH level, the nanoparticles are depolymerized by the poly(disulfide) backbone of P-SS-D. The activated CA consumes the GSH and elevates intracellular H2O2, followed by a high level of Fenton reaction to generate abundant •OH levels. The generation of reactive oxygen species (ROS) further accelerates CA activation. The GSH consumption by disulfide, CA and Fe3+, downregulates GPX4 and generates •OH, which accelerate lipid peroxides (LPO) accumulation and consequently enhances ferroptosis. Additionally, the released Gd3+ may serve as a contrast agent for tumor-specific T1-weighted magnetic resonance imaging (MRI). Thus, the rationally designed FCS/GCS system is a promising strategy for effective MRI-based visual ferroptosis therapy. STATEMENT OF SIGNIFICANCE: Ferroptosis is a new form of non-apoptotic regulated cell death and has potential as an effective supplement to apoptosis-based cancer treatment. However, the efficiency of ferroptosis is limited by excessive glutathione level and insufficient hydrogen peroxide level in tumor site. In this study, we fabricate a theranostic nanoplatform (FCS/GCS) to amplify oxidation stress in tumor site for effective ferroptosis-based cancer treatment, and tumor specific magnetic resonance imaging is introduced for supervision. Our nanoplatform may provide a promising strategy for MRI-based visual ferroptosis therapy with high specificity and efficiency.

[Cognition of traditional Chinese medicine properties and thinking of clinical rational use of drug].

This paper discusses the rational use of traditional Chinese medicine based on chemical composition, body state and biological effect. The essence and connotations of traditional Chinese medicine are explained by modern scientific theory and technical means, and the mechanism of traditional Chinese medicine in the treatment of diseases is defined in modern medicine language, which is conducive to promoting rational and safe clinical use of drugs. Based on the chemical composition of traditional Chinese medicine,the selected genuine medicinal materials were collected and processed in a standardized way, and then used in the combination with other traditional Chinese medicines, with the aim to improve the efficacy of traditional Chinese medicine in clinical indications, increase the advantages, eliminate the disadvantages, and adapt to flexible and safe clinical drug demands. Based on the body state elements, clinical diagnosis and treatment shall be patient-centered, and doctors shall distinguish the differences of pathogenesis, symptoms and diseases, and consider the drug contraindications of special groups. According to the " dose-effect-toxicity" relationship, doctors shall select the appropriate dosage form, control the drug dosage, balance the benefits and risks of drugs, and carry out appropriate medical treatment. Based on the biological effect elements and the regulatory mechanism of traditional Chinese medicine on the target and pathway of disease, traditional Chinese medicine shall strengthen the precise positioning, provide accurate treatment; evaluate the safety of traditional Chinese medicine combination, explore the adverse reaction mechanism, strengthen the clinical safety monitoring of traditional Chinese medicine, and guide the clinical rational use of drugs, in the expectation of ensuring the safe use of traditional Chinese medicine and maximize the clinical efficacy of traditional Chinese medicine.

[Clinical comprehensive evaluation of Wenxin Granules in treatment of arrhythmia with deficiency of Qi and Yin].

This study evaluated the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine of Wenxin Granules in the treatment of arrhythmia(ventricular premature beat and atrial premature beat) with deficiency of Qi and Yin. The multi-criteria decision analysis(MCDA) model was adopted, and the criterion layer and index layer were weighted by experts. CSC v2.0 was used for clinical comprehensive evaluation. This study embodies the clinical value of Wenxin Granules, promotes its safe, effective and rational use, and provides a basis for national medical decision-making. The multi-source evidence shows that the major adverse reaction of Wenxin Granules is gastrointestinal damage. According to the available studies, Wenxin Granules has controllable risk and thus is rated as grade B in terms of safety. The systematic evaluation of effectiveness shows that compared with antiarrhythmic western medicine, Wenxin Granules demonstrates improved clinical efficacy and electrocardiogram efficacy, which is supported by high-quality evidence, and thus the effectiveness of Wenxin Granules is evaluated as grade A. Economic research shows that Wenxin Granules is more economical than antiarrhythmic western medicine, which is supported by sufficient evidence and clear results, and thus the economy of this preparation is rated as grade B. The indications and contraindications of Wenxin Granules are clear and detailed to different types of arrhythmia, which, together with the precise positioning and prominent clinical innovation and industrial innovation, rates it as grade A in terms of innovation. The suitability of drug storage, prescription circulation, dosage form and course of treatment basically meet the clinical medication needs of doctors and patients, and thus the suitability of Wenxin Granules is evaluated as grade B. Because of the few restrictions and the sustainable resources of medicinal materials, the accessibility of Wenxin Granules is evaluated as grade A. The prescription compatibility focuses on the pathogenesis characteristics of deficiency of Qi and Yin, and there are more than 3 000 cases studied. Therefore, the characteristics of traditional Chinese medicine of Wenxin Granules are evaluated as grade B. Based on the evidence from all the above dimensions, Wenxin Granules has the clinical comprehensive value of class A and prominent characteristics of traditional Chinese medicine. It is suggested to include Wenxin Granules into the policy results related to basic clinical medication management according to the procedure.

[Report standards for clinical comprehensive evaluation of Chinese patent medicine].

The clinical comprehensive evaluation of drugs is an important basis for the return of clinical value, decision-making of medical and health authorities, and allocation of medical resources. In July 2021, the National Health Commission issued the Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), which required the evaluation to be implemented from the six dimensions(safety, effectiveness, economy, innovation, suitability, and accessibility), and made detailed arrangements for the clinical comprehensive evaluation of drugs. As Chinese patent medicine differs from chemical medicines in terms of effective components and action modes, the clinical comprehensive evaluation of Chinese patent medicine should highlight the characteristics and advantages of traditional Chinese medicine(TCM) on the basis of general requirements of comprehensive clinical evaluation of drugs. At present, in the clinical comprehensive evaluation of Chinese patent medicine, unified report standards have not yet been generated, resulting in the uneven quality of existing reports. To standardize the clinical comprehensive evaluation report of Chinese patent medicine and improve its quality, the editorial team, based on the relevant policy documents of clinical comprehensive evaluation of drugs, formulated the clinical comprehensive evaluation report standards for Chinese patent medicine in combination with the previous practice and expert opinions. The report standards, containing seven sections with 15 items determined, focus on data source, evaluation content, evidence synthesis, quality control, and evaluation results supported with detailed interpretations to help researchers better understand and apply the report standards for clinical comprehensive evaluation of Chinese patent medicine, improve the report quality, and provide references for the decision-making by the national medical management authorities.

[Study of integrative evidence chain in clinical trial of Guizhi Fuling Capsules based on "Yibing Tongzhi" in clinical applications].

Guizhi Fuling Capsules is a new-type traditional Chinese medicine preparation made by modern process method. It was widely used to treat uterine fibroids, pelvic inflammation, dysmenorrhea, endometriosis, mammary gland hyperplasia and other gynecological diseases. Under the combination of disease and syndrome, the diagnosis and treatment model of "Yizheng Tongbing, Yibing Tongzhi" with Chinese patent medicine has been widely used in clinical practice. Meanwhile, the effectiveness and safety have been given more and more attention. Based on the effectiveness of Guizhi Fuling Capsules, this paper preliminarily summarized the dominant diseases in randomized controlled trials and systematic reviews of Guizhi Fuling Capsules. On the basis of the basic theory of traditional Chinese medicine and modern pharmacological mechanism, the clinical efficacy and mechanism of Guizhi Fuling Capsules were explored. Finally, according to the traditional Chinese medicine theory of "Yizheng Tongbing, Yibing Tongzhi", all the clinical evidences were integrated to form an integrated evidence chain, so as to provide guidance for the safe and rational use of Guizhi Fuling Capsules.

[Analysis on 1 500 adverse reactions of Guizhi Fuling Capsules based on spontaneous response system].

To understand the characteristics of adverse reactions and find early warning signs after intake of Guizhi Fuling Capsules. The 1 500 adverse reaction(ADR) cases of Guizhi Fuling Capsules obtained by spontaneous reporting system(SRS) from 2008 to 2017 were analyzed by proportional reporting ratios method(PRR), Bayesian confidence propagation neural network method(BCPNN) and propensity score method. The number of ADR reports increased year by year, and reached the peak in the fourth quarter of 2014. A total of 1 500 ADR cases were monitored, including 10 severe ADR cases. There were a total of 934 cases aged between 18-44 years old, accounting for 62.27%. All patients were orally administered. Among them, 1 398 patients received a single dose according to the package insert, and 57.4% had ADR within 24 h. The top five clinical manifestations of ADR were gastric dysfunction, abdominal pain, nausea, vomiting and rash, which mainly damaged the digestive system. The ADR signals were analyzed. PRR suggested that "gastric dysfunction" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. BCPNN suggested that "nausea" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. After the propensity score weighting method was used to control the confounding factors, the warning signals remained unchanged. The results show that Guizhi Fuling Capsules has fewer adverse reactions and is relatively safe. This study provides a basis for studying ADR of Guizhi Fuling Capsules, and guidance for drug vigilance and risk management of Guizhi Fuling Capsules.

[Analysis of Qingkailing Injection in treatment of combined medication features of 2 147 cases of upper respiratory tract infection].

Acute upper respiratory infection is one of the common infectious diseases,especially in the elderly people. Qingkailing Injection has the effect of clearing away heat and detoxifying. It can be used for external wind heat,upper respiratory tract infection,viral cold,etc. Based on 2 147 cases of upper respiratory tract infection patients using Qingkailing Injection in the medical electronic data warehouse of the information system of 16 large class-A hospitals constructed by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,description analysis,Apriori calculation and recurrent network analysis were used to analyze the effect of Qingkailing Injection on upper respiratory tract infection. The clinical characteristics and the law of combined use of drugs can provide reference for the mining of clinical diagnosis and treatment characteristics and the construction of optimal and effective programs and paths. 2 147 patients with upper respiratory tract infection who used Qingkailing Injection were mostly middle-aged and elderly people over 45 years old,often combined with hypertension,ischemic cerebrovascular disease,coronary heart disease,diabetes,etc.; in treatment,it was more common to use Qingkailing Injection in combination with hormones,antipyretics and analgesics,antibiotics,nutritional support agents,antitussive,expectorant and antiasthmatic drugs,as well as traditional Chinese medicine Jiebiao agents and blood management agents. The combination of potassium chloride injection and cephalosporin injection is the most commonly used in combination with two kinds of Western medicine( 33. 2%); the combination of Shuanghuanglian and Ganmao Qingre Granules is the most commonly used in combination with two kinds of traditional Chinese medicine( 9. 13%); through the calculation of complex network group module,it is found that Qingkailing Injection is often associated with antibiotics,antipyretic and analgesic drugs,antitussive,expectorant and antiasthmatic drugs,antiviral drugs and anti infection drugs. Drugs,nutritional support agents,bronchodilators,immunomodulators and other chemical drugs are often used in combination with Chinese medicine,such as Jiebiao agents,expectorants,Qingre agents,resuscitation agents,Qufeng agents,tonics,Liqi agents,which may be related to both the treatment of upper respiratory tract infection and the basic diseases of middle-aged and elderly patients,with the theoretical characteristics of " combination of disease and syndrome,corresponding formula and syndrome". Based on the real world big data complex network group module mining results provide clues for the clinical optimization scheme and path construction,and provide signals and ideas for further causal research.

[Post-marketing surveillance on Guizhi Fuling Jiaonang based on literature review].

To systemically evaluate the post-marketing safety of Guizhi Fuling Jiaonang. Computer retrieval was conducted in Medline, EMbase, the Web of Science, Clinical Trials. Gov, the Cochrane Library, CNKI, VIP, WanFang Data and CBM to collect relevant information. The papers were then screened according to inclusion and exclusion criteria. A total of 234 papers were included in this study, including 164 randomized controlled trials, 7 quasi-randomized controlled trials, 8 non-randomized controls, 56 case series, and 1 cohort study. The patients were only treated with Guizhi Fuling Jiaonang in 56 studies, and Guizhi Fuling Jiaonang was combined with other drugs in 178 studies. The total ADRs/AEs incidence was 1.99% in single use of Guizhi Fuling Jiaonang, and 8.21% in combined use, but showing no severe adverse reactions. Gastrointestinal system damage was most common in mild ADRs. In this study, it was found that the overall safety of Guizhi Fuling Jiaonang was acceptable. The direct evidences of the drug's safety case reports were systematically analyzed in this study, but the mechanism study on the safety of the drug after marketing or the prospective long-term clinical observation study was not sufficient, so the further studies on the safety of drug use should be conducted in order to provide better guidance for clinical medication.

The Efficacy of Hyperbaric Oxygen Therapy on Middle Cerebral Artery Occlusion in Animal Studies: A Meta-Analysis.

BACKGROUND: Inconsistent results have been reported for hyperbaric oxygen therapy (HBO) for acute stroke. We conducted a systematic review and meta-analysis to evaluate the benefit of HBO in animal studies of middle cerebral artery occlusion (MCAO). METHODS: A systematic search of the literature published prior to September 2015 was performed using Embase, Medline (OvidSP), Web of Science and PubMed. Keywords included "hyperoxia" OR "hyperbaric oxygen" OR "HBO" AND "isch(a)emia" OR "focal cerebral ischemia" OR "stroke" OR "infarct" OR "middle cerebral artery occlusion (MCAO)." The primary endpoints were the infarct size and/or neurological outcome score evaluated after HBO treatment in MCAO. Heterogeneity was analyzed using Cochrane Library's RevMan 5.3.5. RESULTS: Fifty-one studies that met the inclusion criteria were identified among the 1198 studies examined. When compared with control group data, HBO therapy resulted in infarct size reduction or improved neurological function (32% decrease in infarct size; 95% confidence interval (CI), range 28%-37%; p < 0.00001). Mortality was 18.4% in the HBO group and 26.7% in the control group (RR 0.72, 95% CI, 0.54-0.98; p = 0.03). Subgroup analysis showed that a maximal neuro-protective effect was reached when HBO was administered immediately after MCAO with an absolute atmospheric pressure (ATA) of 2.0 (50% decrease; 95% CI, 43% -57% decrease; p < 0.0001) and more than 6 hours HBO treatment (53% decrease; 95% CI, 41% -64% decrease; p = 0.0005). CONCLUSIONS: HBO had a neuro-protective effect and improved survival in animal models of MCAO, especially in animals given more than 6 hours of HBO and when given immediately after MCAO with 2.0 ATA.

Ginkgo biloba on focal cerebral ischemia: a systematic review and meta-analysis.

Gingko biloba extract (EGB) has been used in traditional medicines for centuries, and although its application to cerebral ischemia has been of great interest in recent years, high quality evidence-based clinical trials have not been carried out. This systematic review and meta-analysis aimed to examine the neuroprotective effect of EGB on focal cerebral ischemia in animal models. A systematic literature search was performed using five databases spanning January 1980-July 2013. The outcome was assessed using the effect size, which was based on infarct size and/or neurological score. A total of 42 studies with 1,232 experimental animals matched our inclusion criteria. The results revealed that EGB improved the effect size by 34% compared to the control group. The animal species, the method and time to measure outcome, and the route and dosage of EGB administration affected the variability of the effect size. Mechanisms of EGB neuroprotection were reported as anti-apoptotic, anti-oxidative, and anti-inflammatory. In conclusion, EGB exerts a significant protective effect on experimental focal cerebral ischemia. However, possible experimental bias should be taken into account in future clinical studies.

A systematic review and meta-analysis of buyang huanwu decoction in animal model of focal cerebral ischemia.

Buyang Huanwu Decoction (BHD) is a well-known Chinese herbal prescription for ischemic stroke. The objective of this systematic review and meta-analysis is to provide the current evidence for neuroprotective effects of BHD and its possible mechanisms in animal models of focal ischemia. A systematic literature search, through October 2012, was performed using six databases. The outcome measures assessed were infarct size and/or neurological score. Fifty-six studies with 1270 animals that met the inclusion criteria were identified. The median score for methodological quality was 3 with a range of 2 to 6. Compared with vehicle or no treatment controls, BHD gave a 37% improvement in outcome for all doses ranging from 1.0 g/kg to 60 g/kg at each time point that BHD was administered (P < 0.01). Efficacy was higher in mouse models that utilized suture occlusion and temporary ischemia. The neuroprotective effects of BHD are involved in multiple mechanisms and act upon multiple cell types. In conclusion, BHD possesses substantial neuroprotective effects in experimental stroke probably as a result of the multitarget therapy strategy typically utilized in traditional Chinese medicine. Future research should examine the presence of possible experimental bias and an in-depth study of herbal compound preparations.