Clinical efficacy and safety of compound Congrong Yizhi Capsules on Alzheimer's disease in mainland China: A systematic review with trial sequential analysis and GRADE assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a degenerative disease of the central nervous system (CNS) with insidious onset. AD is also the most common cause of dementia. Compound Congrong Yizhi Capsules (CCYC), a traditional Chinese medicine compound developed by the team of Beijing University of Chinese Medicine, has been widely used to treat AD. AIM OF THIS STUDY: To systematically evaluate the clinical efficacy and safety of CCYC for AD by meta-analysis, Trial Sequential Analysis (TSA) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. METHODS: This study was registered at PROSPERO (CRD42022295496). Randomized controlled trials (RCTs) of CCYC as the treatment for AD published before December 1, 2021 were retrieved from 4 Chinses databases, 4 English databases and 2 clinical trials registration systems. RevMan 5.4 and STATA 17.0 was used to conduct the meta-analysis of the included studies, the quality of outcomes was rated by the GRADE system, the TSA was conducted by TSA 0.9.5.10 software. RESULTS: Seven studies were included, and the total sample size was 746. Meta-analysis showed that 6 months of treatment with CCYC plus conventional western medicine treatments (CTs) improved MMSE scores compared with CTs alone (WMD: 4.32, 95% CI: 3.23, 5.42), and TSA confirmed that more trials in the future will not reverse the result. Among which, CCYC combined with donepezil can significantly improve MMSE scores (WMD: 3.54, 95% CI: 2.86, 4.22). CCYC combined with olanzapine also showed good effect on both MMSE (WMD: 6.49, 95% CI: 5.54, 7.44) and ADL scores (WMD: 5.23, 95% CI: 4.63, 5.83). No serious adverse events were reported. The strengths of the evidences above are MODERATE. CONCLUSION: CCYC combined with cognition-modifying western medicine can improve cognitive function, mental behavioural symptoms, and activities of daily living in AD patients with good safety.

An overview of the evidence to guide decision-making in acupuncture therapies for early recovery after acute ischemic stroke.

Background: Acupuncture is a proven technique of traditional Chinese medicine (TCM) for ischemic stroke. The purpose of this overview was to summarize and evaluate the evidence from current systematic reviews (SRs) of acupuncture for early recovery after acute ischemic stroke (AIS). Methods: We performed a comprehensive search for SRs of acupuncture for AIS in seven electronic databases up to May 23, 2022. Two reviewers independently selected SRs, extracted data, evaluated the methodological quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and rated evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results: Seven SRs were included. The overall methodological quality of SRs was critically low. As for GRADE, 3 outcomes had moderate-quality evidence, 14 had low-quality evidence, and 12 had very low-quality evidence. Moderate-quality evidence demonstrated that initiating acupuncture therapies within 30 days of AIS onset significantly improves neurological function and the total effective rate of patients. Low-quality evidence showed that for patients within 2 weeks of AIS onset Xingnao Kaiqiao acupuncture (XNKQ Ac) could reduce disability rate and might reduce mortality. Regarding the safety of acupuncture therapies, low-quality evidence showed that there was no difference in the incidence of adverse reactions between the 2 groups, and very-low quality evidence showed that acupuncture did not promote hemorrhagic conversion. Conclusions: In the acute and early recovery phases after AIS onset, acupuncture is a promising therapeutic strategy to improve the curative effect of current treatments, especially in the recovery of neurological function. Patients in the acute phase might receive XNKQ Ac, and patients in the early recovery phase might receive EA1, CA, or SA. However, considering the current certainty of evidence, a solid recommendation warrants further exploration.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022335426.

An Overview of Systematic Reviews of Chinese Herbal Medicine in the Treatment of Migraines.

Background: In the past, systematic reviews (SRs) and meta-analyses (MAs) have been used to assess the efficacy of Chinese herbal medicine (CHM) in the treatment of migraines. However, robust conclusions have not yet been determined because of variations in the methodological and evidence quality of these SRs/MAs. Objectives: We aimed to assess the methodological and reporting quality of SRs/MAs and evaluate the available evidence of the efficacy of CHM treatment of migraines. Methods: We searched eight electronic databases from inception until 10 January 2022, without language restrictions. Two researchers were independently responsible for study screening and data extraction. The methodological and reporting quality of SRs/MAs were assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2 and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The evidence quality of included SRs/MAs was evaluated by Grading of Recommendations Assessment, Development and Evaluation (GRADE). In addition, a descriptive analysis of the included SRs/MAs was included. Results: Sixteen SRs/MAs, including 69 outcomes, were finally included in this overview. Data synthesis of the included SRs/MAs outcomes showed that CHM plus Western medicine (WM) was beneficial in the improvement of migraines. In comparison, there was conflicting evidence for the effectiveness of CHM used alone. CHM was better than WM in improving responder rate and acute medication usage and was superior to placebo in improving migraine days, responder rate, and migraine duration. However, there was insufficient evidence to verify the effectiveness of CHM for migraine treatment regarding pain severity and migraine frequency. All the included SRs/MAs showed extremely low methodological and reporting quality. The results of the GRADE system indicated that the quality of most of the pooled evidence was very low. Conclusions: CHM may be beneficial in improving migraines and can be used as a complementary therapy. However, we should treat the conclusions of the evaluated SRs/MAs cautiously because of the low quality of evidence. Future SRs/MAs should focus on improving methodological and reporting quality. High-quality randomized controlled trials (RCTs) are needed to provide strong evidence for the efficacy of CHM treatment of migraines.

Rehmannioside A improves cognitive impairment and alleviates ferroptosis via activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway after ischemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmannioside A is derived from Rehmannia glutinosa Libosch, which is widely used as an important ingredient in diverse traditional Chinese medicines to treat diseases caused by "kidney deficiency" such as cerebral arteriosclerosis, aging-related stroke and dementia in China. Recent studies have proved that Rehmannia glutinosa Libosch and Rehmannioside A can improve memory capability and recover nerve damage. AIM OF THE STUDY: To investigate the effect of Rehmannioside A on cognitive impairment after ischemia in rats and SH-SY5Y cells, and further evaluate the anti-oxidative and anti-ferroptosis mechanisms. MATERIALS AND METHODS: Differentially expressed proteins (DEPs) in patients after cerebral ischemic stroke were revealed by a RayBio protein array. Cognitive impairment model was established by middle cerebral artery occlusion and reperfusion (MCAO) 14 days in rats. Rehmannioside A was administered intraperitoneally injection at dose of 80 mg/kg. The SH-SY5Y cells were exposed to H2O2 for 24 h and treated with Rehmannioside A (80 µM) for 24 h. The neuroprotecion of Rehmannioside A were evaluated by infarct volume (TTC), neurological defects (Garcia score) and learning memory (Morris water maze test) in vivo, and cell viability (CCK-8 or LDH) in vitro. Superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO) activity of rats, glutathione (GSH), oxidized glutathione (GSSG) and nicotinamide adenine dinucleotide phosphate (NADPH) of cells were detected by biochemical assay. Intracellular reactive oxygen species (ROS) were measured by DCFH-DA assay. Myeloperoxidase (MPO), PI3 kinase (PI3K), p-PI3K, Akt, p-Akt, heme oxygenase-1 (HO-1), nuclear factor-E2-related factor 2 (Nrf2), SLC7A11, glutathione peroxidase 4 (GPX4) of the cerebral cortex in rats or SH-SY5Y cells were examined by western blotting. RESULTS: Compared with model group, the cognitive impairment and neurological deficits of Rehmannioside A group were significantly improved, and the cerebral infarction was reduced in MCAO rats. Moreover, the cell viability obviously increased and the H2O2-induced toxicity was reduced in Rehmannioside A group. Further research indicated that the expression of p-PI3K, p-Akt, nuclear Nrf2, HO-1 and SLC7A11 in Rehmannioside A group was significantly higher than model group. CONCLUSION: Rehmannioside A has neuroprotection effect and improves cognitive impairment after cerebral ischemia by inhibiting ferroptosis and activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway. These findings provide valuable insight into the pathogenesis and therapeutic target of ischemic stroke.

[Evidence of clinical randomized controlled trial study in treatment of acute cerebral infarction with traditional Chinese medicine in recent five years].

To systematically search and sort out the clinical randomized controlled trial(RCT) on the prevention and treatment of acute cerebral infarction with traditional Chinese medicine(TCM) by using the method of evidence map, and to understand the evidence distribution of related studies. CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Cochrane Library and Web of Science were retrieved from January 2016 to September 2020, and literatures related to the prevention and treatment of acute cerebral infarction with traditional Chinese medicine were included. Text description combined with table and bubble chart were used to analyze the distribution characteristics of evidence. A total of 1 102 clinical articles in recent five years were retrieved. The annual trend of clinical study publication, study size, TCM therapy category and main scheme, and study literature quality were analyzed. We find that TCM treatment of acute cerebral infarction has become a hot topic of clinical research, the number of literature showed a trend of increased year by year, various means of intervention of TCM in the treatment of the advantages of increasingly highlight. Follow-up clinical research should highlight the characteristics of TCM: in the analysis of outcome indicators; increase the neuropsychological patients after stroke and cognitive ability, and the theory of combined treatment of TCM disease when thoughts; At the same time, the quality of clinical research needs to be improved. At present, there is still a lack of unified standards for the production of evidence map. This study is the first to explore the application of evidence map to summarize and display the clinical research status of TCM treatment of acute cerebral infarction, and combine it with the setting of priority areas of TCM clinical research, so as to provide a reference basis for determining the priority topic selection of TCM treatment optimization research.

[Analysis of status quo of outcome indicators of randomized controlled trials in treatment of acute ischemic stroke with acupuncture in recent three years].

To analyze the use of outcome indicators of randomized controlled trial(RCT) of acupuncture in the treatment of acute ischemic stroke in recent three years, so as to provide a basis for building a study on the core outcome indicators for the treatment of acute ischemic stroke with acupuncture. The RCTs of acupuncture treatment for acute ischemic stroke in recent three years were collec-ted through computer retrieval of eight Chinese and English databases and two clinical trial registries at home and abroad. Literature was screened out, and data was extracted. Risk of assessment bias tool Cochrane 6.1 was used for bias risk assessment, outcome indicators were summarized and analyzed. A total of 47 RCTs were included, and 3 studies were trials registration scheme. Outcome indicators were divided into 6 categories according to functional attributes, namely physical symptoms/signs, physical and chemical examination, quality of life, traditional Chinese medicine symptoms/syndromes, safety events and long-term prognosis. The study found that in addition to the common problems in previous studies covered by the status quo of outcome indicators selection of RCT of acupuncture in the treatment of acute ischemic stroke, there were also the other problems as follows: emphasis on macroscopic efficacy indicators but neglect of acupuncture specific indicators, lack of characteristic indicators and economic indicators of traditional Chinese medicine therapy, and unification of indicators measurement tool and measurement time point. In the future, the outcome indicators set for the treatment of acute ischemic stroke with acupuncture shall be established, and the core outcome indicators set shall be in line with the characteristics of traditional Chinese medicine treatment.

[Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of cerebral ischaemic stroke].

There have been many clinical trials, systematic reviews/Meta-analysis proving that Xingnaojing Injection has a good clinical efficacy in treatment of cerebral ischaemic stroke, but with fewer comprehensive descriptions. In this study, an overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treating cerebral ischaemic stroke was performed to provide current situation of evidences and basis for clinical practice. CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science were retrieved through computers. A total of 6 literatures were included in this study. By AMSTAR-2 checklist and GRADE, the quality of included systematic reviews and the efficacy of Xingnaojing Injection were evaluated. The results of AMSTAR-2 checklist showed an extremely low quality for all of the 6 systematic reviews. According to the results of GRADE evaluation, among 55 outcomes, there were 2 outcomes with a medium quality, 4 outcomes with a low quality and 49 outcomes with an extremely low quality. The 6 systematic reviews reached a consistent conclusion that Xingnaojing Injection was effective in the treatment of cerebral ischaemic stroke. This therapy could improve the total efficacy, neurological deficit scores, hemodynamic and hemodynamic parameters. However, the methodolo-gical quality of all literatures was extremely low. The evidence levels of outcomes were between extremely low to medium. The effectiveness of Xingnaojing Injection in the treatment of cerebral ischaemic stroke still needs to be further verified by more high-quality studies. In the future, relevant clinical studies and systematic reviews/Meta-analysis shall be carried out in a strict accordance with relevant regulations.

[Overview of systematic reviews of Panax notoginseng saponins in treatment of acute cerebral infarction].

To overview the systematic reviews of Panax notoginseng saponins in the treatment of acute cerebral infarction. CNKI, CBM, Wanfang, VIP, PubMed, Cochrane Library and EMbase databases were retrieved to collect the systematic reviews of the efficacy of P. notoginseng saponins in the treatment of acute cerebral infarction. The retrieval time was from the time of database establishment to January 2021. After two researchers independently screened out the literature and extracted the data, AMSTAR-2 scale was used to evaluate the methodological quality of the included systematic reviews, GRADE system was used to grade the quality of evidences of the outcome indicators, and the efficacy evaluation was summarized. A total of 5 systematic reviews were included. AMSTAR-2 evaluation results showed that 3 items were relatively complete, while 4 items had a poor overall quality. P. notoginseng saponins combined with conventional Western medicine therapy was superior to single conventional therapy in the recovery of neurological function, enhancement of the total effective rate in clinic, and improvement of activities of daily living. GRADE evaluation results showed that the quality of evidence was from low quality to very low quality. In conclusion, in the treatment of acute cerebral infarction, P. notoginseng saponins can improve the clinical efficacy, with a good safety but a not high methodological quality and a low evidence quality. It is suggested that high-quality clinical studies shall be further carried out to provide evidence-based basis for the application of P. notoginseng saponins in the treatment of acute cerebral infarction.

Systematic Review and Meta-Analysis on Randomized Controlled Trials on Efficacy and Safety of Panax Notoginseng Saponins in Treatment of Acute Ischemic Stroke.

OBJECTIVE: To assess the efficacy and safety of PNS on antiplatelet therapy in the treatment of AIS. METHODS: We searched 7 literature databases and 2 clinical studies databases for randomized controlled studies (RCTs) evaluating PNS as an adjuvant therapy for AIS. Relevant studies were retrieved and screened, and data were extracted independently by two reviewers. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool. Meta-analysis was carried out with the Rev Man 5.4 software. RESULTS: Of 8267 records identified, 43 RCTs met our inclusion criteria (n = 4170 patients). Patients assigned to PNS with conventional treatments (CTs) had improved functional independence at 90 days compared with those assigned to CTs alone (RR = 1.87, 95% CI = 1.37, to 2.55, P < 0.0001). Patients who received PNS combined with CTs showed significantly high improvements in neurological function among individuals with AIS on the neurologic deficit score (NDS) (MD CSS = -5.71, 95% CI = -9.55 to -1.87, P=0.004; MD NIHSS = -3.94, 95% CI = -5.65 to -2.23, P < 0.00001). The results also showed PNS contributed to a betterment in activities of daily living (ADL) on the Barthel index (MD day 10 BI = 4.86, 95% CI = 2.18, to 7.54, P < 0.00001; MD day 14 BI = 13.92, 95% CI = 11.46 to 16.38, P < 0.00001; MD day 28 BI = 7.16, 95% CI = 0.60, to 13.72, P < 0.00001). In addition, PNS, compared with CTs alone, could significantly improve overall response rate (ORR) (RR NIHSS = 1.20, 95% CI = 1.16, to 1.24, P < 0.00001; RR CSS = 1.15, 95% CI = 1.08, to 1.24, P < 0.0001), hemorheological parameters, maximum platelet aggregation rate (MPAR) (MD = -6.82, 95% CI = -9.62 to -4.02, P < 0.00001), platelet parameters (MD PLT = 4.85, 95% CI = 1.82 to 7.84, P=0.002; MD MPV = -0.79, 95% CI = -1.09 to -0.48, P < 0.00001), and serum CD62P (MD = -0.21, 95% CI = -0.29 to -0.13, P < 0.00001). The incidence of adverse reactions in PNS was lower than that in the control group (RR = 0.62, 95% CI = 0.39 to 0.97, P=0.04). Adverse reactions in the PNS were mild adverse reactions. CONCLUSION: PNS may be effective and safe in treating AIS on ameliorating neurological deficit, improving activities of daily living function, and enhancing antiplatelet effects. However, more high-quality evidence is needed before it can be recommended for routine antiplatelet therapy in patients with AIS.