Fine-tuning pH sensor H98 by remote essential residues in the hydrogen-bond network of mTASK-3.

TASK-3 generates a background K+ conductance which when inhibited by acidification depolarizes membrane potential and increases cell excitability. These channels sense pH by protonation of histidine residue H98, but recent evidence revealed that several other amino acid residues also contribute to TASK-3 pH sensitivity, suggesting that the pH sensitivity is determined by an intermolecular network. Here we use electrophysiology and molecular modeling to characterize the nature and requisite role(s) of multiple amino acids in pH sensing by TASK-3. Our results suggest that the pH sensor H98 and consequently pH sensitivity is influenced by remote amino acids that function as a hydrogen-bonding network to modulate ionic conductivity. Among the residues in the network, E30 and K79 are the most important for passing external signals near residue S31 to H98. The hydrogen-bond network plays a key role in selectivity or pH sensing in mTASK-3, and E30 and S31 in the network can modulate the conductive properties (E30) or reverse the pH sensitivity and selectivity of the channel (S31). Molecular dynamics simulations and pK1/2 calculation revealed that double mutants involving H98 + S31 primarily regulate the structure stability of the pore selectivity filter and pore loop regions, further strengthen the stability of the cradle suspension system, and alter the ionization state of E30 and K79, thereby preventing pore conformational change that normally occurs in response to varying extracellular pH. These results demonstrate that crucial residues in the hydrogen-bond network can remotely tune the pH sensing of mTASK-3 and may be a potential allosteric regulatory site for therapeutic molecule development.

Efficacy and safety of the Chaixiong Qiwei granule for tension-type headache: study protocol for a randomised controlled trial.

INTRODUCTION: Tension-type headache (TTH) is the most prevalent headache disorder worldwide. Although current treatments for TTH are beneficial, they are not without adverse effects. Chaixiong Qiwei granule (CXQW) is an experienced prescription medicine for TTH management. This study will evaluate the efficacy and safety of CXQW for the treatment of TTH. METHODS AND ANALYSIS: This study will be a multicentre, randomised, double-blind, placebo-controlled trial. A total of 148 eligible participants will be divided into the intervention (CXQW treatment) and control (placebo treatment) groups. The primary outcome will be the reduction in the number of headache days (headache-days reduction) within 9-12 weeks after randomisation, while secondary outcomes will include the number of headache days, headache intensity, responder rate, drug consumption for acute treatment, quality of life and symptoms related to traditional Chinese medicine use based on a symptom-observation table. This protocol describes the design of the randomised controlled trial. ETHICS AND DISSEMINATION: The study design was approved by the Institutional Review Board of Human Research at Xiyuan Hospital, China Academy of Chinese Medical Sciences (No. 2020XLA030-2). TRIAL REGISTRATION NUMBER: ChiCTR2100042514.

Research trends and hotspots of post-stroke cognitive impairment: a bibliometric analysis.

Background: Post-stroke cognitive impairment (PSCI) is a major complication of stroke that affects more than one-third of stroke survivors, threatening their quality of life and increasing the risk of disability and death. Although various studies have described the etiology, epidemiology, and risk factors of PSCI, there are a limited number of comprehensive and accurate reports on research trends and hotspots in this field. Therefore, this review aimed to evaluate research trends, hotspots, and frontiers in PSCI using bibliometric analysis. Methods: We screened the literature spanning 20 years in the Web of Science Core Collection: Science Citation Index Expanded (SCI-Expanded) database from 1 January 2003 to 31 December 2022. We included all eligible literature reports based on our comprehensive search strategy, inclusion criteria, and exclusion criteria. The analysis of annual publications, countries/regions, institutions, journals, co-cited references, and keywords was conducted using CiteSpace and VOSviewer, and the hotspots and major findings of PSCI were summarized. Results: A total of 1,024 publications were included in this review. We found that the number of publications on PSCI increased annually. These publications were published in 75 countries or regions by over 400 institutions. Although Chinese institutions had the highest number of publications, their international influence was limited. The United States showed a strong influence in the field. The journal "Stroke" published the most publications (57) with a high impact factor and was considered the most co-cited journal. The most frequently cited references focused on the prevalence, incidence, neuropsychological assessment scales, criteria, and guidelines of PSCI. The strongest citation burst keywords for PSCI were "neurotrophic factor" and "synaptic plasticity", which were regarded as research focuses and research hotspots, respectively. Conclusion: This review provided a comprehensive summary of the literature of PSCI, identified the authoritative and frequently cited literature and journals, clarified the trends in PSCI research, and highlighted the hotspots in this field. Currently, studies on the mechanisms and treatment of PSCI are limited, and we hope that this review has effectively highlighted the research trajectory of PSCI and will lay the foundation for more innovative research in the future.

A Bibliometric Analysis of Cardioembolic Stroke From 2012 to 2022.

Cardioembolic stroke, a subtype of ischemic stroke with the worst prognosis, is quietly threatening public health. We aimed to visualize the development trend and hotspots of research on cardioembolic stroke. A total of 2886 papers about cardioembolic stroke published from 2012 to 2022 were retrieved in the Web of Science Core Collection (WoSCC) database. Further, we performed a bibliometric analysis of these publications, such as generating cooperation maps, co-citation analysis of journals and references, and cluster analysis of keywords. According to the results, cardioembolic stroke research faces many clinical challenges. We obtained the knowledge maps of countries/institutions, authors, journals with high publications and citations, and representative references in this field. Studies about optimal prevention strategies for cardioembolic stroke, identification of cardioembolism in cryptogenic stroke, and prophylactic anticoagulation for patients with embolic stroke of undetermined source (ESUS) or at high risk of left ventricle (LV) thrombus are in the spotlight.

Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets.

TWIK-related acid-sensitive K+ (TASK) channels, including TASK-1, TASK-3, and TASK-5, are important members of the two-pore domain potassium (K2P) channel family. TASK-5 is not functionally expressed in the recombinant system. TASK channels are very sensitive to changes in extracellular pH and are active during all membrane potential periods. They are similar to other K2P channels in that they can create and use background-leaked potassium currents to stabilize resting membrane conductance and repolarize the action potential of excitable cells. TASK channels are expressed in both the nervous system and peripheral tissues, including excitable and non-excitable cells, and are widely engaged in pathophysiological phenomena, such as respiratory stimulation, pulmonary hypertension, arrhythmia, aldosterone secretion, cancers, anesthesia, neurological disorders, glucose homeostasis, and visual sensitivity. Therefore, they are important targets for innovative drug development. In this review, we emphasized the recent advances in our understanding of the biophysical properties, gating profiles, and biological roles of TASK channels. Given the different localization ranges and biologically relevant functions of TASK-1 and TASK-3 channels, the development of compounds that selectively target TASK-1 and TASK-3 channels is also summarized based on data reported in the literature.

A bibliometric analysis and visualization of tension-type headache.

Background: Tension-type headache (TTH) is the most prevalent headache in the clinical practice, leading to impaired social activities, work-related disability, and heavy financial burdens. Previous studies have described possible inducement, potential pathophysiology, and clinical management of TTH; however, due to the lack of attention, literature involving bibliometric analysis is sporadic. Therefore, this study aimed to explore the current hotspots and future directions of the TTH field by bibliometric analysis. Methods: By using CiteSpace and VOSviewer, literature regarding TTH between 2002 and 2021 from the Web of Science database was summarized and extracted. Annual publication trend, the most productive countries/regions and institutions, distribution of categories, co-citation of journals and references, and co-occurrence of keywords were analyzed. Results: A total of 3,379 publications were included in the final visualization, indicating a stable trend in current research and a lack of breakthroughs over the past decades. These studies were mainly conducted in 120 countries/regions led by the United States and more than 600 institutions. Four eternal core themes were identified in TTH, including neurosciences, nursing, developmental psychology, and general/internal medicine. Cephalalgia ranked first, with the highest number of literature, and is the most influential journal in this area. Keyword analysis demonstrated that the similarities and differences between migraine and TTH, epidemiological studies, clinical double-blind trials, and potential populations have become key issues in the TTH field. Conclusion: TTH has received less attention and breakthroughs in the past 20 years. To promote coordinated development between regions to fight headaches, cooperation and exchanges between countries and institutions are essential in the future. Relevant studies about headaches in children and adolescents, inducing factors such as emotional triggers and sleep disorders, concomitant diseases, possible pathogenesis, and headache treatments, are in the spotlight in recent years. This study offers a powerful roadmap for further research in this field.

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.

A systematic review and meta-analysis for the primary prevention of high risk of stroke by Nao-an capsules.

BACKGROUND: To date, Nao-an capsules are the only Chinese patent medicine primarily prescribed for the primary prevention of stroke. PURPOSE: To evaluate the efficacy and safety of Nao-an capsules in the primary prevention of stroke in high-risk patients. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials. METHODS: We searched 7 electronic databases and 2 registries from inception to January 13, 2022 for relevant randomized controlled trials. Two independent investigators selected trials, collected data, and judged the risk of bias. We performed a meta-analysis using the Review Manager software. RESULTS: Nine randomized controlled trials involving 14 744 patients at high risk of stroke were included. Nao-an capsules reduced the risk of first stroke compared with no intervention (risk ratio [RR] = 0.49, 95 % confidence interval [CI] 0.29 to 0.82, p = 0.006) or aspirin (RR50 mg qd = 0.47, 95 % CI 0.25 to 0.91, p = 0.03; RR100 mg qd = 0.46, 95 % CI 0.22 to 0.99, p = 0.05), without increased bleeding risks. The certainty of evidence was evaluated as moderate to very low. CONCLUSION: In addition to controlling specific risk factors, Nao-an capsules might provide additional preventive effects on first stroke with an acceptable safety profile for populations at high risk of stroke. However, as current evidence is too weak, a firm recommendation depends on further confirmation from more studies with more rigorous methodology.

Efficacy and Safety of Xingnaojing Injection for Emergency Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background: Xingnaojing injection (XNJ) is derived from a traditional Chinese prescription named Angong Niuhuang pill. As an adjuvant treatment widely used in acute ischemic stroke (AIS), XNJ has proven to be effective with certain clinical evidence. The aim of this study is to collect the latest evidence and evaluate efficacy and safety of XNJ for emergency treatment of AIS. Methods: We searched seven literature databases and two clinical trial registries from their inception to November 14, 2021 for randomized controlled trials (RCTs) examining the efficacy of XNJ for AIS. Two reviewers independently selected relevant trials, extracted data, and assessed the risk of bias. We pooled data into a meta-analysis using RevMan 5.4 software. Results: Thirty-eight RCTs were included in this review, with a total of 3,677 participants. XNJ plus conventional treatments (CTs) showed a significant advantage, compared with CTs alone, in improving functional independence at 14 days (RR = 1.70, 95% CI = 1.03 to 2.81, p = 0.04), neurological function (MD NIHSS < 6h = -3.81, 95% CI = -5.25 to -2.38, p < 0.00001; MD NIHSS < 24h = -3.75, 95% CI = -4.92 to -2.59, p < 0.00001; MD NIHSS < 72h = -3.74, 95% CI = -5.48 to -2.00, p < 0.0001; MD NIHSS < 14d = -1.97, 95% CI = -3.25 to -0.69, p = 0.003), and activities of daily living on the Barthel index (MD BI-14day = 9.97, 95% CI = 9.29 to 10.65, p < 0.00001; MD BI-30day = 10.04, 95% CI = 5.82, to 14.26, p < 0.00001). In addition, the results showed that XNJ plus CTs was superior to CTs alone in reducing IL-6, TNF-α, hs-CRP, and MMP-9. Regarding safety of XNJ, the incidence of adverse reactions in the XNJ group was lower than that in the control group (RR = 0.57, 95% CI = 0.38 to 0.87, p = 0.009). The certainty of evidence was evaluated as low or very low for all. Conclusion: XNJ appears to be effective and safe for emergency treatment of AIS. The first 72 h after the onset of stroke, in particular the first 6 hours, may be the optimum initiation time. However, further high-quality RCTs are warranted to determine an appropriate initiation time. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=233211], identifier [CRD42021233211].

Traditional Chinese Medicine for Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

Background: Post-stroke cognitive impairment (PSCI) affects more than one-third of stroke patients, and causes much greater harm to long-term function than the initial brain damage. No conventional Western medications have shown convincing clinical effectiveness for treating PSCI. Research shows that Traditional Chinese medicine (TCM) can improve cognitive function in patients. However, the clinical efficacy and safety remain controversial. The aim of this study was to examine the effectiveness and harmful effects of TCMs in the treatment of PSCI. Method: We searched seven databases and two clinical registration websites for randomized controlled trials (RCTs). The revised Cochrane risk of bias tool (RoB 2.0) was used to evaluate the methodological quality and RevMan 5.4 was used for data analysis. This study has been submitted to PROSPERO with registration number is CRD42020149299. Results: We included 34 studies in this review. The results of this study showed that TCM adjuvant therapy improved scores on the MoCA [MD = 2.55, 95% CI (1.56, 3.53), p < 0.00001; MD = 3.07, 95% CI (1.98, 4.17), p < 0.00001 at treatment duration of <3 and 3 months, respectively], MMSE [MD = 2.55, 95% CI (1.99, 3.10), p < 0.00001; MD = 2.53, 95% CI (1.59, 3.47), p < 0.00001; MD = 2.91, 95% CI (1.26, 4.56), p = 0.0006; MD = 3.11, 95% CI (-0.04, 6.27), p = 0.05 at treatment duration of <3, 3, 4, and 6 months, respectively], and BI [MD = 7.34, 95% CI (3.83, 10.85), p < 0.0001; MD = 8.98, 95% CI (4.76, 13.21), p < 0.0001 at treatment duration of <3 and 3 months, respectively] and reduced scores on the ADL (MD = -8.64, 95% CI (-9.83, -7.45), p < 0.00001; MD = -2.00, 95% CI (-2.94, -1.06), p < 0.0001 at treatment duration of 3 and 4 months, respectively], NIHSS [MD = -2.48, 95% CI (-4.97, 0.00), p = 0.05; MD = -3.81, 95% CI (-6.21, -1.40), p = 0.002 at treatment duration of <3 and 3 months, respectively], and CSS [MD = -2.47, 95% CI (-3.49, -1.45), p < 0.00001 at a treatment duration of 3 months]. No serious adverse reactions were observed. Conclusion: Despite the significant positive results, the present evidence supports, to a limited extent because of the methodological flaws and herbal heterogeneity, that TCM adjuvant therapy can be used for patients with PSCI. While, further rigorous RCTs are warranted to confirm the efficacy and safety of TCM. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42020149299.

[Outcome indicators in randomized controlled trials on traditional Chinese medicine intervention for tension-type headache in recent five years].

To evaluate the application of outcome indicators in randomized controlled trials(RCTs) concerning the treatment of tension-type headache(TTH) with traditional Chinese medicine(TCM) in recent five years, so as to provide a basis for the study of core outcome set(COS) for TCM intervention in TTH. The RCTs on TCM treatment of TTH in recent five years were systematically retrieved from CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov and China Clinical Trial Registry. After literature screening, data extraction and evaluation of the risk of bias, the outcome indicators in the included RCTs were subjected to qualitative analysis. The preliminary search yielded 19 042 articles, and 10 983 were left after the elimination of duplication. Finally, 52 RCTs(48 in Chinese and 4 in English) were included for qualitative analysis. The outcome indicators of RCTs included in this study were classified into seven domains: TCM syndrome, symptom and sign, physical and chemical detection, quality of life, long-term prognosis, economic evaluation, and safety event. The findings demonstrated that headache characteristic index in the symptom and sign domain was the index with the highest reporting frequency and reporting rate. Seventeen RCTs used TCM syndrome score as the outcome indicator. Further analysis revealed that there existed such problems in research design as non-distinction between primary and secondary outcome indicators, great difference in the adopted measurement tools for outcome indicators, and the neglect of measurement time of outcome indicators. Moreover, the syndrome indicators reflecting TCM advantages, objective evaluation indicators, safety and health-economic indicators were lacking. These limitations have affected the quality and reliability of RCTs on TTH treatment with TCM. It is suggested that the efficacy and characteristics of TCM should be combined into current clinical research, and the COS in RCTs regarding TCM treatment of TTH should be established according to internationally recognized standard procedures.

[Systematic review and Meta-analysis of efficacy and safety of gastrodin in treatment of tension-type headache].

The efficacy of gastrodin as a Chinese herbal medicine extract in the treatment of tension-type headache has been confirmed. This paper systematically reviewed the efficacy and safety of gastrodin in the treatment of tension-type headache, aiming to provide a new choice for the treatment of this disease. In this study, four Chinese databases, four English databases and two trial registries were searched from the date of establishment to September 2020. The related randomized controlled trials(RCTs) were screened out according to the predetermined criteria. The bias risk assessment tool developed by Cochrane collaboration was used to evaluate the quality of the reports. RevMan 5.4.1 was used for Meta-analysis, and GRADE system for the evidence-based evaluation on the quality of outcome indicators. A total of 177 articles were retrieved and 8 articles were finally included for analysis, with a total sample size of 1 091 cases, which included 565 cases in the treatment group and 526 cases in the control group. The overall quality of included stu-dies was not high. The results of Meta-analysis are as follows:(1)In terms of headache frequency, gastrodin group was better than wes-tern medicine group(MD=-2.90, 95%CI[-3.76,-2.03], P<0.000 01).(2)In terms of number of abnormal blood vessels in TCD, gastrodin group was better than western medicine group(MD=-88.96, 95%CI[-102.36,-75.55], P<0.000 01).(3)In terms of effective rate, gastrodin group was better than western medicine group(RR=1.47, 95%CI[1.29, 1.68], P<0.000 01). The results of subgroup analysis are as follows:(1)Effective rate based on age, for the patients upper age limit 40-46 years old, gastro-din group was better than western medicine group(RR=1.69, 95%CI[1.50, 1.90], P<0.000 01); for the patients upper age limit 55-60 years old, gastrodin group was better than western medicine group(RR=1.27, 95%CI[1.16, 1.38], P<0.000 01).(2)Effective rate based on dosage form, both the gastrodin capsules and injection groups were better than western medicine group(RR_(capsules)=1.42, 95%CI[1.08, 1.88], P=0.01; RR_(injection)=1.50, 95%CI[1.26, 1.77], P<0.000 01). GRADE evaluation showed that the above outcomes had low quality of evidence. Only one article detailed the occurrence of adverse reactions and thus the present study cannot make a positive conclusion on the safety of gastrodin in the treatment of tension-type headache. The small number and low quality of the included reports affected the reliability of the results. In the future, more high-quality randomized controlled trails are needed to improve the evaluation on the efficacy and safety of gastrodin in the treatment of tension-type headache.

[Systematic review and Meta-analysis of efficacy and safety of Toutongning Capsules in treatment of tension-type headache].

This study aims to systematically evaluate the clinical efficacy and safety of Toutongning Capsules in the treatment of tension-type headache(TTH), so as to provide a corresponding basis for clinical treatment. Eight commonly used medical research databases and two clinical trial registration systems were retrieved with the time interval from the establishment of the database or system to November 2020. The randomized controlled trials of Toutongning Capsules in the treatment of TTH were screened out according to the pre-set criteria. The quality of the included papers was evaluated by the bias risk assessment tool in Cochrane Reviewers Handbook 6.1 and the data were statistically analyzed by RevMan v5.4 provided by Cochrane collaboration. A total of 13 studies were included and the quality of methodology was generally low. Meta-analysis showed that Toutongning Capsules assisted with western medicine therapy can effectively reduce the pain intensity(MD_(VAS)=-1.94,95%CI[-2.50,-1.38],P<0.000 01;MD_(NRS)=-0.83,95%CI[-0.86,-0.80],P<0.000 01), headache duration(SMD=-0.98,95%CI[-1.17,-0.79],P<0.000 01), headache frequency(MD=-1.01,95%CI[-1.16,-0.85],P<0.000 01), headache index(MD=-11.13,95%CI[-12.10,-10.16],P<0.000 01), anxiety and depression scale score(MD_(HAMA)=-4.02,95%CI[-6.58,-1.46],P=0.002;MD_(HAMD)=-2.67,95%CI[-4.04,-1.29],P=0.000 1), while Toutongning Capsules as monotherapy only reduced the headache score(MD=-2.24,95%CI[-2.97,-1.51],P<0.000 01). The available clinical studies demonstrate that Toutongning Capsules combined with western medicine in the treatment of TTH can improve the related outcome indicators, but the clinical safety and efficacy of Toutongning Capsules alone remain unclear. Due to the small number and low quality of the included studies, large-sample, multi-center, high-quality and strictly designed randomized controlled trials are still needed to verify the clinical efficacy in the future.

Efficacy and Safety of DL-3-n-Butylphthalide in the Treatment of Poststroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

Background: Poststroke cognitive impairment (PSCI) is a common complication observed after stroke. Current pharmacologic therapies have no definitive evidence for cognitive recovery or disease progression. Recent studies have verified the positive effect of DL-3-n-butylphthalide (NBP). However, the clinical efficacy and safety are still unclear. The aim of this study was to assess the efficacy of NBP and its harmful effect in the treatment of PSCI. Method: Eligible randomized controlled trials (RCTs) were retrieved from inception to June 2021 from seven medical databases and two clinical registries. The revised Cochrane risk of bias tool (RoB 2.0) was used for methodological quality. RevMan v5.4.1 from Cochrane Collaboration was used for statistical analysis, and Hartung-Knapp-Sidik-Jonkman (HKSJ) method was used for post hoc testing depend on the number of studies. This study has been submitted to PROSPERO with registration number is CRD42021274123. Result: We identified 26 studies with a total sample size of 2,571 patients. The results of this study showed that NBP as monotherapy or combination therapy had better performance in increasing the MoCA (monotherapy: SMDN = 1.05, 95% CI [0.69, 1.42], p < 0.00001; SMDP = 1.06, 95% CI [0.59, 1.52], p < 0.00001. combination: SMDO = 0.81, 95% CI [0.62, 1.01], p < 0.00001; SMDN = 0.90, 95% CI [0.46, 1.33], p < 0.0001; SMDD = 1.04, 95% CI [0.71, 1.38], p < 0.00001), MMSE (monotherapy: MDN = 4.89, 95% CI [4.14, 5.63]), p < 0.00001). combination: SMDO = 1.26, 95% CI [0.97, 1.56], p < 0.00001; SMDC = 1.63, 95% CI [1.28, 1.98], p < 0.00001; SMDN = 2.13, 95% CI [1.52, 2.75], p < 0.00001) and BI (monotherapy: MDN = 13.53, HKSJ 95% CI [9.84, 17.22], p = 0.014. combination: SMDO = 2.24, HKSJ 95%CI [0.37, 4.11], p = 0.032; SMDC = 3.36, 95%CI [2.80, 3.93], p < 0.00001; SMDD = 1.48, 95%CI [1.13, 1.83], p < 0.00001); and decreasing the NIHSS (monotherapy: MDN = -3.86, 95% CI [-5.22, -2.50], p < 0.00001. combination: SMDO = -1.15, 95% CI [-1.31, -0.98], p < 0.00001; SMDC = -1.82, 95% CI [-2.25, -1.40], p < 0.00001) and CSS (combination: MDO = -7.11, 95% CI [-8.42, -5.80], p < 0.00001), with no serious adverse reactions observed. The funnel plot verified the possibility of publication bias. Conclusion: NBP maintains a stable pattern in promoting the recovery of cognitive function and abilities of daily living, as well as reducing the symptoms of neurological deficits. However, there is still a need for more high-quality RCTs to verify its efficacy and safety.