Abstract
Background. Evidence regarding the effect of Panax notoginseng saponins (PNS) on treating elderly stroke patients is scare and inconsistent. This study investigated the efficacy and safety of PNS by means of meta-analysis so as to provide an evidence-based reference for the treatment of elderly patients with stroke. Methods. We searched the PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, Wanfang, and China Biomedical Database to identify the eligible randomized controlled trials (RCTs) concerning using PNS to treat elderly people with stroke from their inception to first, May 2022. Meta-analysis was used for pool analysis of the included studies, whose quality was assessed via Cochrane Collaboration’s RCT risk of bias tool. Results. Altogether 206 studies published between 1999 and 2022 with a low risk of bias were included, covering 21,759 participants. The results showed that the improved neurological status shown in the intervention group with PNS alone was statistically significant (SMD = −0.826, 95% CI: −0.946 to −0.707) in contrast to the control group. The total clinical efficacy (Relative risk (RR) = 1.197, 95% Confidence interval (CI): 1.165 to 1.229) and daily living activities (SMD = 1.675, 95% C: 1.218 to 2.133) of elderly stroke patients were significantly improved as well. In addition, the invention group using PNS combined with WM/TAU displayed significant improvement in neurological status (SMD = −1.142, 95% CI: −1.295 to −0.990) and the total clinical efficacy (RR = 1.191, 95% CI: 1.165 to 1.217) compared with the control group. Conclusion. Single PNS intervention or PNS combined with WM/TAU significantly improves the neurological status, the overall clinical efficacy and daily living activities of elderly stroke patients. However, more multicenter RCT research with high quality is required in the future to verify the results in this study. The trial registration number: Inplasy protocol 202330042. doi:10.37766/inplasy2023.3.0042.
1. Introduction
Stroke, a major cause of disability and death, is a common disease among elderly people. As the second cause of death among people aged over 60 around the world, its mortality is on the rise every year. China has the highest incidence of stroke, where 1,763 out of 100,000 people suffer from ischemic stroke per year [1]. Meanwhile, disability rate of stroke is as high as 75% in China [2]. According to a report from Global Burden of Disease, 1.7 million people died from stroke in 2010 [3]. In recent years, stroke has become the first cause of death in China [4]. According to statistics, from 2015 to 2018, around 2% of people over 40 years old had a stroke, up to 50% of whom were no more than 64, which suggest that the average age of stroke onset is going down. With a high rate of prevalence, disability and mortality, stroke has thus become a global public health concern.
Internationally, the main treatment adopted now for stroke is still vascular recanalization (thrombolysis and endovascular interventional therapy), whose effect [5, 6], however, is enjoyed by only a few patients due to factors such as short time window, high cost, and limited medical level. Panax notoginseng saponins (PNS), with the functions of dispersing blood stasis and hemostasis, reducing swelling and relieving pain, is widely used for treating stroke in China. Modern pharmacological studies believe that PNS can reduce the infarct size of ischemic stroke, inhibit edema [7], protect the blood-brain barrier, reduce nerve damage, and inhibit relevant inflammation [8, 9]. Commonly used PNS products mainly include oral-type products, such as Xueshuantong capsule (XC), Xuesaitong soft capsule (XSC), Sanqi Tongshu capsule (STC), and compound Xueshuantong capsule (CXC), and injection type products, such as Xueshuantong capsule, Xuesaitong soft capsule, Sanqi Tongshu capsule, and compound Xueshuantong capsule.
With the increase of age, the elderly are more susceptible to stroke hemiplegia because of gradually declining body function and continually weakening cardiovascular system. For these patients, Western medicine (WM) often adopts recovery treatment that helps improve movement function to a certain extent, but rehabilitation cannot be achieved [10]. Although PNS has been extensively used for treating stroke and many clinical trials have confirmed its clinical efficacy and safety [11, 12], whether it is effective and safe for the elderly population remains to be investigated. However, related evidence-based studies for this age group were rarely reported and the majority of previous studies measured only a single stroke outcome (eg., clinical efficacy). Furthermore, there were many problems with the methodological quality of previous studies. For instance, the studies included had low quality and serious bias, which may adversely affect the credibility of evidence and confuse subsequent clinical practice and health decision-making. As a result, this study, targeting at the elderly population, comprehensively analyzed the efficacy and safety of PNS in multiple outcomes by meta-analysis in order to provide more systematic clinical evidence for clinical medication and health decision-making concerning elderly stroke patients.
2. Methods
This study was reported in strict accordance with the Priority Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) [13]. All the analyses were based on previously published studies, and therefore, no ethical approval and participants’ consent were required.
2.1. Search Strategies and Study Selection
Based on the standard of the Cochrane Collaboration, a comprehensive literature search, without restrictions on publication time, literature type, or region, was conducted to identify randomized controlled trials (RCTs) related to treating elderly stroke patients with PNS from their inception to first, May 2022, in PubMed, Embase, Cochrane library, Web of Science, CNKI, VIP, Wanfang, and China Biomedical Database. References in the included studies, related conference abstracts, published research papers and gray literature in the form of government reports, etc., are all consulted in case of leaving out any potentially useful data. The literature search was performed based on the combination of subject words and free words. The Chinese search terms included stroke, cerebral infarction, cerebral embolism, cerebral apoplexy, ischemic stroke, ischemic stroke, Panax notoginseng saponins, blood embolism Tong, Xueshuantong, Sanqi Tongshu Capsules, and randomized controlled trials. The English search terms were Xueshuantong capsule, Sanqi Tongshu capsule, Xuesaitong soft capsule, brain infarction, compound Xueshuantong, cerebral infarction, stroke, brain embolism, ischemic stroke, cerebrovascular disorders, and RCT. The specific search strategies of each database were attached in Appendix.
After the initial search, the collected studies were screened to remove duplicates. Ineligible articles were filtered out according to their titles and abstracts. For the remaining potentially relevant results, their full texts were reviewed and assessed according to our screening criteria, during which ineligible articles were excluded, numbered, and then registered with the reasons why they were ruled out. For texts with incomplete information or problems, we evaluated their eligibility after contacting the author.
2.2. Inclusion and Exclusion Criteria
In this study, the screening criteria conformed with the PICOS (population, intervention, comparators, outcomes, and study design) principles of the Cochrane Collaboration to assess the quality of studies. Detailed information is listed below.
2.3. Population
The symptoms of the population were in line with the relevant diagnostic criteria for stroke both at home and abroad and were confirmed as ischemic stroke by medical imaging tests such as MRI or CT. International criteria formulated by the World Health Organization, the National Center for Neurological Disorders and Stroke Research, and the Japanese Ministry of Health and Welfare were considered. Domestic criteria include ischemic stroke in arteriosclerosis thrombosis cerebral infarction, cerebral embolism, and lacunar cerebral infarction diagnosis standard set by National Cerebrovascular Disease Conference, Stroke Therapeutic Effect Evaluation Standard of Traditional Chinese Medicine (TCM) Diagnosis set by the Chinese Institute of TCM, Tentative Evaluation Standard for Stroke Diagnosis and Therapeutic Effect set by the State Administration of TCM Encephalopathy Emergency research consortium in 1995, Diagnostic Basis, Syndrome Classification and Therapeutic Effect Evaluation of Stroke in The Traditional Chinese Medicine Industry Standard of People’s Republic of China—Standard of Diagnosis and Curative effect Evaluation of TCM Disease, and the classification standard in Chinese Classification of Cerebrovascular Diseases 2015 [14]. The subject groups were older adults with an average age of over 60, regardless of gender or race [15].
2.4. Intervention
Intervention involves single use of PNS such as Xuesaitong injection, Xueshuantong injection, Lulutong injection, Sanqitongshu capsule, Xuesaitong soft capsule, Xuesaitong Tablets, Xueshuantong Capsules, and Xuesaitong Dropping Pills, combined use of PNS and WM or PNS and treatment as usual (TAU).
2.5. Comparator
All the patients in the controlled group underwent conventional routine treatment to improve their cerebral blood supply and drug treatment, such as taking medication to nourish their brain tissues. Conventional therapy in WM, which followed Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2015 [5], includes intravenous thrombolysis, endovascular therapy, antiplatelet, anticoagulation, decrease of fibrinogen, increase of blood volume, improvement of cerebral circulation, nutrition of nerves, lipid regulation, blood pressure reduction, hypoglycemia, and rehabilitation. The regular treatments for the controlled groups and the treated groups must be the same, and the course of treatment is not limited.
2.6. Outcomes
Measurement for the outcomes should be clearly defined and includes at least one of the following items: neurological deficit score, the clinical response rate, and assessment of activities of daily living (ADLs).
2.7. Study Design
All the included studies were RCTs or clinical controlled trials. The study design adopted RCT. In other words, “random grouping” should be mentioned in the article or its grouping method was “tossing a coin,” “drawing lots,” “rolling dice,” “random number table,” “computer coding,” “block randomization,” or “stratified randomization.”
2.8. Exclusion Criteria
Exclusion criteria were as follows: (1) research with duplicate publications or duplicate data; (2) research with incomplete data or serious errors; (3) research without the full text; (4) research involving unconventional treatments in Western medicine such as Chinese herbs or acupuncture; (5) observational research, fundamental research based on cell or animal specimens, experience summaries, review papers, and case study reports.
2.9. Outcome Measures and Data Extraction
The primary outcome measure was the post-treatment neurological deficit score graded by the National Institutes of Health Stroke Scale (NIHSS). Secondary outcome measures included (1) overall clinical response rate [16] and (2) posttreatment ADL score.
The included studies were numbered for the convenience of reviewing. Basic information and data in these studies consisted of title, authors, publication year, specific treatments, number of cases, sample ages, male to female ratio, experimental design methodologies (including randomized method, blind method and the like), key factors for evaluating risk of bias, the outcome measures and the results, the course of treatment, etc.
2.10. Quality Assessment of the Included Studies
The risk of bias in the included studies was assessed via the Cochrane Collaboration’s RCT risk of bias tool [17]. There were 7 assessed items random sequence generation, allocation concealment, blinding of participants and intervention providers, blinding of outcome assessors, outcome completeness, selective reporting of outcomes, and other sources of bias, which were rated as low, and unclear or high bias level. The assessment of included RCTs was separately conducted by two researchers, who then exchanged the results and checked. Disagreement would first be discussed by the two researchers, who would refer to the supervision researcher if they could not reach a consensus. Finally, the risk of bias map was drawn with RevManand Office software.
2.11. Statistical Analyses
Categorical data (such as the overall clinical response rate) were to be combined and measured by relative risk (RR) and numerical data (such as neurological deficit score, and the activity of daily living score) by standard mean difference (SMD), whose 95% of confidence interval (CI) was calculated. The heterogeneity of the included studies was measured by the chi-square test (with a significant level of 0.1) and judged by the value of I2 at the same time. During the meta-analysis, when statistically significant heterogeneity (P < 0.10 or I2 > 50%) was shown, the random effect model would be chosen; otherwise, (P ≥ 0.10 or I2 ≤ 50%) the fixed effect model would be applied [18]. For significant heterogeneity, subgroup, or sensitivity analysis or only descriptive analysis was conducted to deal with the data. If more than ten studies were concerned with one certain variable, the publication bias would be assessed by a funnel plot and Egger’s test [19]. The above data analyses were done with the help of Software STATA (Version 14.0, Stata, Corp, College Station, TX).
3. Results
3.1. Literature Screening
The initial database search yielded 5,542 articles and 5,351 remained after removing duplicates by Endnote. Then, 545 articles were removed by checking titles and abstracts, and 120 articles were excluded from the rest after the full text review. Finally, 206 eligible papers were included for quantitative analysis. The detailed information on literature screening is presented in Figure 1 [13, 20].
3.2. Characteristics of the Included Studies
This study collected 206 RCTs for analysis, with 21,759 participants involved, among whom 11,118 were randomly distributed in the intervention group and 10,641 in the controlled group. All included articles were published between 1999 and 2022, 204 of which are Chinese. The average age of participants was 63.20 years old with 12,502 male participants, accounting for 57.46%. The course of treatment varied from 3 days to 6 months. 108 studies reported acute stroke period, 4 studies reported the recovery period, and 94 did not report the information of stroke periods. See Table 1 for all basic information on the included studies.
3.3. Quality Assessment
All of the 206 articles were RCTs, which were considered low risk of bias in the generation of random sequences. Without clarifying allocation concealment, 143 articles were rated unclear risk of bias. 15 articles reported blinding of participants and 41 used blinding for assessors. All included studies were at low risk of bias in terms of outcome completeness. 7 articles were rated as low risk for selective reporting bias. For other bias, 38 and 168 studies were at unclear and low risk of bias, separately. Detailed information on the quality assessment of the included studies were introduced in Table 2 and Figure 2. Moreover, certainty assessment of the included studies was shown in Table 3.
3.4. Primary Outcome: Neurological Deficit Score
Centered on applying single PNS to treatment, 59 articles involving 6,045 participants reported information on neurological deficit. The intervention group significantly improved the neurological conditions of elderly stroke patients (SMD = −0.826, 95% CI:−0.946 to −0.707; I2 = 78.9%, Pheterogeneity < 0.001) (Table 4 and Figure 3) [16]. The funnel plot and Egger’s test results indicated no publication bias (P = 0.066) (Figure 4).
By contrast, 100 articles involving 10,347 participants reported information on neurological deficit after the treatment of combining PNS with WM/TAU. Similarly, the intervention group showed a significant improvement in the neurological conditions (SMD = −1.142, 95% CI:−1.295 to −0.990; I2 = 92.1%, Pheterogeneity < 0.001) (Table 4 and Figure 5) of elderly stroke patients. There was no hint of publication bias in the funnel plot and Egger’s test results (P < 0.001) (Figure 6).
3.5. Secondary Outcomes: Total Clinical Efficacy
There were 77 articles reporting the outcomes of overall clinical efficacy for using PNS alone, involving 8,589 participants. Our results indicated that, compared to the controlled group, the overall clinical efficacy of the PNS alone group showed statistically significant difference (RR = 1.191, 95% CI: 1.165 to 1.217; I2 = 52.9%, Pheterogeneity<0.001) (Table 4 and Figure 7). The funnel plot and Egger’s test results revealed hint of publication bias (P < 0.001) (Figure 8).
For the intervention group using PNS combined with WM/TAU, 100 articles reported the outcome of overall clinical efficacy, with 10,249 participants involved. Compared with the controlled group, there was statistical significance in the overall clinical efficacy of PNS combined with WM/TAU in treating elderly stoke (RR = 1.191, 95% CI: 1.165 to 1.217; I2 = 42.8%, Pheterogeneity<0.001), as shown in Table 4 and Figure 9. Hint of publication bias was observed in the funnel plot and Egger’s test results (P < 0.001) (Figure 10).
3.6. Activities of Daily Living Score
There were 11 articles reporting ADLs of 839 elderly stroke patients who were treated with PNS alone. As shown in Table 4, elderly stroke patients in the intervention group who were treated with PNS displayed significant improvement in their ADLs (RR = 1.675, 95% CI: 1.218 to 2.133; I2 = 87.7%, Pheterogeneity<0.001) (Table 4 and Figure 11). The funnel plot and Egger’s test results hinted the existence of publication bias (P = 0.012) (Figure 12).
As for the effect of PNS combined with WM/TAU on ADLs in elderly stroke patients (SMD = 1.034, 95% CI: 0.900 to 1.168; I2 = 77.8%, Pheterogeneity<0.001) (Table 4 and Figure 13), 44 articles with 4,508 participants showed that compared to the controlled group, elderly stroke patients in the intervention group did not improve significantly. The funnel plot and Egger’s test results indicated hint of publication bias (P = 0.003) (Figure 14).
3.7. Subgroup Analysis
Due to the significant heterogeneity of total clinical efficacy, subgroup analysis was conducted based on the following variables: area (developed vs. developing areas), publication year (before vs. and after 2015), sample size (less vs. no less than 100), and male to female ratio (below vs. not below one). The analysis results showed that, for the single PNS intervention, heterogeneity mainly came from articles published before 2015 (Table 4). For the intervention group using PNS combined with WM/TAU, the primary source of heterogeneity was articles with a sample size of less than 100 or with a male to female ratio of less than 1. Results of the analyses revealed that the source of heterogeneity potentially correlated with publication year, treatment duration, and total sample size as well as region development condition. The subgroup analysis results are shown in Table 4.
4. Discussion
In this study, 206 articles involving 21,759 participants were collected for meta-analysis. The results showed that compared with the controlled group, single PNS or PNS combined with WM/TAU significantly improved the neurological status, overall clinical efficacy, and ADLs of elderly stroke patients.
In clinical treatment for ischemic stroke, antiplatelet, statin, and antihypertension were the three “cornerstones” [21]. However, the application of WM hit a bottleneck due to issues such as drug resistance, impairment of liver and kidney function, and interactions caused by the co-use of multiple drugs and the like. On the strength of traditional Chinese medicine theory and experience, Chinese medical workers have achieved favorable results in preventing and treating cerebrovascular diseases with natural medicines. After extensively reviewing and analyzing 206 PNS-related clinical trials, this study confirmed the effectiveness of PNS in the treatment of stroke in the elderly population and provided a theoretical basis for treating them in the field of traditional Chinese medicine.
As a traditional Chinese medicine with a history of over 600 years, PNS has the functions of promoting blood circulation, removing blood stasis, reducing swelling, relieving pain, etc. PNS products, such as Sanqitongshu capsule, are mainly composed of panaxtriol saponins (PTS), a component in Sanqi capable of promoting blood circulation and removing blood stasis [22, 23]. By now, the mechanism of PNS is still unclear. It is likely that PTS reduces endothelin levels in the peripheral blood, increases cerebral blood supply to ischemic areas, regulates blood hypercoagulability, and improves the microcirculation in ischemic brain tissue [24]. The major active component in PTS, Rg1 (accounting for 60%), and R1 and Re (accounting for 20%), can improve cerebral ischemic dysfunction, restore ischemic cerebral metabolic abnormalities, resist platelet aggregation, and reduce blood viscosity in the treatment of cerebral arterial thrombosis. In addition, Rg1 enhances the activity of the fibrinolytic system, promotes the release of nitric oxide from the vascular endothelium, and thus, has an antithrombotic effect [25]. For ischemic reperfusion injury, PNS can reduce calcium overload, cerebral edema, and structural damage and promote nerve repair during reperfusion [26] and help reduce mortality during ischemic-reperfusion. What is more, relevant studies show that PNS enhances the ischemic tolerance of the brain and reduces the recurrence of fatal ischemic brain injury, which is beneficial to the secondary prevention of ischemic stroke [27].
PNS has a wide range of pharmacological effects, including scavenging free radicals and antioxidative stress, inhibiting inflammatory factors, blocking calcium ion channels, improving microcirculation and energy metabolism, etc. These effects account for the favorable results of PNS in the treatment of ischemic cerebrovascular disease. PNS can dilate cerebral blood vessels so that cerebrovascular resistance reduces and cerebral blood flow increases. For animals, experimental results indicated that mean blood pressure (BMP) and cerebrovascular resistance (CVR) of anaesthetized rabbits and rats are reduced after the intervention of PNS, depending on the dosage used, but their cerebral blood flow did not increase [28]. PNS for injection, made of Sanqi, has high bioavailability, rapid action, and definite curative effect, which, however, is likely to cause adverse reactions, because it is complicatedly composed, the content of its active components and impurities is difficult to control, and it acts on multiple aspects of the brain. Therefore, it is essential to specify the ingredients and their doses in the injectable PNS so that the quality of the injection as well as the safety of patients can be ensured [28]. Related preparation research explained that compound Xueshuantong capsules effectively reduce blood viscosity, inhibit platelet activation and aggregation, enhance vasodilation regulation function, and increase fibrinase activity, thereby mitigating the cerebrovascular injury caused by oxidative stress response due to ischemic oxygen feeding. Additionally, compound Xueshuantong capsules reduce blood viscosity, regulate blood lipids, and block calcium ion channels, which is conducive to the recovery of cranial nerve function [29–32]. Oral PNS can be used for treating acute stroke by way of multi-target and multi-path. It can improve cerebral blood supply, repair nerve function, narrow the infarct size, and improve the clinical prognosis displaying the clinical advantages of traditional Chinese medicines.
Subgroup analysis discovered that PNS intervention or PNS combined with WM/TAU improved the overall clinical efficacy, neurological status, and ADLs of elderly stroke patients. Sources of heterogeneity probably came from articles with smaller sample sizes or older publications. Conclusions drawn from these articles were less reliable and the evidence was not fully updated, consequently giving rise to heterogeneity in our meta-analysis results.
To our knowledge, this is the first meta-analysis of the clinical efficacy and safety of PNS in the treatment of elderly stroke patients. Based on extensive experimental data, this study made a scientific and objective evaluation of the efficacy and safety of PNS in the treatment of acute elderly stroke. Additionally, clinical application of the study provided an objective and reliable evidence-based reference for the follow-up research, nursing staff, clinical workers, and health policy decision makers. However, there were some limitations. For one thing, some of the articles involved were of relatively low quality, with unclear randomization methods, allocation concealment, and uncalculated sample size, which affected the reliability of the conclusion in this study. For another, the fact that all the included studies are Chinese led to linguistic bias in the results. Therefore, follow-up studies should carefully be designed, implemented, and reported following the standard of RCTs [33]. Moreover, we found a moderate to high heterogeneity across our study, which might directly affect the reliability of our evidence. Although by implementing subgroup analyses based on the primary results, we identified the sources of heterogeneity caused by different treatment duration and regional development condition in different literature, there were still other hidden elements affecting the measured effect of PNS in this study. Consequently, it is crucial to carry out multi-center and larger-sample RCTs on treating elderly stroke patients with PNS so as to provide guidance for clinical treatment and follow-up research.
5. Conclusion
Our study found that PNS intervention or PNS combined with WM/TAU significantly improved the neurological function, DLAs, and the overall clinical efficacy in elderly stroke patients. Considering the quality of the included studies, the results of this study should be interpreted with caution. And it is necessary to conduct more multi-center RCTs with high quality to explore the efficacy and safety of PNS for elderly stroke patients in the future, thus contributing more reliable primary data to evidence-based decision-making.
Appendix
A. PubMed
#1 “Stroke” [Mesh] #2 (((((((((((((((((((((((((((Strokes[Title/Abstract]) OR (Cerebrovascular Accident[Title/Abstract])) OR (Cerebrovascular Accidents[Title/Abstract])) OR (CVA (Cerebrovascular Accident[Title/Abstract]))) OR (CVAs (Cerebrovascular Accident[Title/Abstract]))) OR (Cerebrovascular Apoplexy[Title/Abstract])) OR (Apoplexy, Cerebrovascular[Title/Abstract])) OR (Vascular Accident, Brain[Title/Abstract])) OR (Brain Vascular Accident[Title/Abstract])) OR (Brain Vascular Accidents[Title/Abstract])) OR (Vascular Accidents, Brain[Title/Abstract])) OR (Cerebrovascular Stroke[Title/Abstract])) OR (Cerebrovascular Strokes[Title/Abstract])) OR (Stroke, Cerebrovascular[Title/Abstract])) OR (Strokes, Cerebrovascular[Title/Abstract])) OR (Apoplexy[Title/Abstract])) OR (Cerebral Stroke[Title/Abstract])) OR (Cerebral Strokes[Title/Abstract])) OR (Stroke, Cerebral[Title/Abstract])) OR (Strokes, Cerebral[Title/Abstract])) OR (Stroke, Acute[Title/Abstract])) OR (Acute Stroke[Title/Abstract])) OR (Acute Strokes[Title/Abstract])) OR (Strokes, Acute[Title/Abstract])) OR (Cerebrovascular Accident, Acute[Title/Abstract])) OR (Acute Cerebrovascular Accident[Title/Abstract])) OR (Acute Cerebrovascular Accidents[Title/Abstract])) OR (Cerebrovascular Accidents, Acute[Title/Abstract]) #3 (“Stroke” [Mesh]) OR ((((((((((((((((((((((((((((Strokes[Title/Abstract]) OR (Cerebrovascular Accident[Title/Abstract])) OR (Cerebrovascular Accidents[Title/Abstract])) OR (CVA (Cerebrovascular Accident[Title/Abstract]))) OR (CVAs (Cerebrovascular Accident[Title/Abstract]))) OR (Cerebrovascular Apoplexy[Title/Abstract])) OR (Apoplexy, Cerebrovascular[Title/Abstract])) OR (Vascular Accident, Brain[Title/Abstract])) OR (Brain Vascular Accident[Title/Abstract])) OR (Brain Vascular Accidents[Title/Abstract])) OR (Vascular Accidents, Brain[Title/Abstract])) OR (Cerebrovascular Stroke[Title/Abstract])) OR (Cerebrovascular Strokes[Title/Abstract])) OR (Stroke, Cerebrovascular[Title/Abstract])) OR (Strokes, Cerebrovascular[Title/Abstract])) OR (Apoplexy[Title/Abstract])) OR (Cerebral Stroke[Title/Abstract])) OR (Cerebral Strokes[Title/Abstract])) OR (Stroke, Cerebral[Title/Abstract])) OR (Strokes, Cerebral[Title/Abstract])) OR (Stroke, Acute[Title/Abstract])) OR (Acute Stroke[Title/Abstract])) OR (Acute Strokes[Title/Abstract])) OR (Strokes, Acute[Title/Abstract])) OR (Cerebrovascular Accident, Acute[Title/Abstract])) OR (Acute Cerebrovascular Accident[Title/Abstract])) OR (Acute Cerebrovascular Accidents[Title/Abstract])) OR (Cerebrovascular Accidents, Acute[Title/Abstract])) #4 “Ischemic Stroke” [Mesh] #5 (((((((((((((((((((((((Ischemic Strokes[Title/Abstract]) OR (Stroke, Ischemic[Title/Abstract])) OR (Ischemic Stroke[Title/Abstract])) OR (Ischemic Strokes[Title/Abstract])) OR (Stroke, Ischemic[Title/Abstract])) OR (Cryptogenic Ischemic Stroke[Title/Abstract])) OR (Cryptogenic Ischemic Strokes[Title/Abstract])) OR (Ischemic Stroke, Cryptogenic[Title/Abstract])) OR (Stroke, Cryptogenic Ischemic[Title/Abstract])) OR (Cryptogenic Stroke[Title/Abstract])) OR (Cryptogenic Strokes[Title/Abstract])) OR (Stroke, Cryptogenic[Title/Abstract])) OR (Cryptogenic Embolism Stroke[Title/Abstract])) OR (Cryptogenic Embolism Strokes[Title/Abstract])) OR (Embolism Stroke, Cryptogenic[Title/Abstract])) OR (Stroke, Cryptogenic Embolism[Title/Abstract])) OR (Wake-up Stroke[Title/Abstract])) OR (Stroke, Wake-up[Title/Abstract])) OR (Wake up Stroke[Title/Abstract])) OR (Wake-up Strokes[Title/Abstract])) OR (Acute Ischemic Stroke[Title/Abstract])) OR (Acute Ischemic Strokes[Title/Abstract])) OR (Ischemic Stroke, Acute[Title/Abstract])) OR (Stroke, Acute Ischemic[Title/Abstract]) #6 (“Ischemic Stroke”[Mesh]) OR ((((((((((((((((((((((((Ischemic Strokes[Title/Abstract]) OR (Stroke, Ischemic[Title/Abstract])) OR (Ischemic Stroke[Title/Abstract])) OR (Ischemic Strokes[Title/Abstract])) OR (Stroke, Ischemic[Title/Abstract])) OR (Cryptogenic Ischemic Stroke[Title/Abstract])) OR (Cryptogenic Ischemic Strokes[Title/Abstract])) OR (Ischemic Stroke, Cryptogenic[Title/Abstract])) OR (Stroke, Cryptogenic Ischemic[Title/Abstract])) OR (Cryptogenic Stroke[Title/Abstract])) OR (Cryptogenic Strokes[Title/Abstract])) OR (Stroke, Cryptogenic[Title/Abstract])) OR (Cryptogenic Embolism Stroke[Title/Abstract])) OR (Cryptogenic Embolism Strokes[Title/Abstract])) OR (Embolism Stroke, Cryptogenic[Title/Abstract])) OR (Stroke, Cryptogenic Embolism[Title/Abstract])) OR (Wake-up Stroke[Title/Abstract])) OR (Stroke, Wake-up[Title/Abstract])) OR (Wake up Stroke[Title/Abstract])) OR (Wake-up Strokes[Title/Abstract])) OR (Acute Ischemic Stroke[Title/Abstract])) OR (Acute Ischemic Strokes[Title/Abstract])) OR (Ischemic Stroke, Acute[Title/Abstract])) OR (Stroke, Acute Ischemic[Title/Abstract])) #7 ((“Stroke”[Mesh]) OR ((((((((((((((((((((((((((((Strokes[Title/Abstract]) OR (Cerebrovascular Accident[Title/Abstract])) OR (Cerebrovascular Accidents[Title/Abstract])) OR (CVA (Cerebrovascular Accident[Title/Abstract]))) OR (CVAs (Cerebrovascular Accident[Title/Abstract]))) OR (Cerebrovascular Apoplexy[Title/Abstract])) OR (Apoplexy, Cerebrovascular[Title/Abstract])) OR (Vascular Accident, Brain[Title/Abstract])) OR (Brain Vascular Accident[Title/Abstract])) OR (Brain Vascular Accidents[Title/Abstract])) OR (Vascular Accidents, Brain[Title/Abstract])) OR (Cerebrovascular Stroke[Title/Abstract])) OR (Cerebrovascular Strokes[Title/Abstract])) OR (Stroke, Cerebrovascular[Title/Abstract])) OR (Strokes, Cerebrovascular[Title/Abstract])) OR (Apoplexy[Title/Abstract])) OR (Cerebral Stroke[Title/Abstract])) OR (Cerebral Strokes[Title/Abstract])) OR (Stroke, Cerebral[Title/Abstract])) OR (Strokes, Cerebral[Title/Abstract])) OR (Stroke, Acute[Title/Abstract])) OR (Acute Stroke[Title/Abstract])) OR (Acute Strokes[Title/Abstract])) OR (Strokes, Acute[Title/Abstract])) OR (Cerebrovascular Accident, Acute[Title/Abstract])) OR (Acute Cerebrovascular Accident[Title/Abstract])) OR (Acute Cerebrovascular Accidents[Title/Abstract])) OR (Cerebrovascular Accidents, Acute[Title/Abstract]))) OR ((“Ischemic Stroke”[Mesh]) OR ((((((((((((((((((((((((Ischemic Strokes[Title/Abstract]) OR (Stroke, Ischemic[Title/Abstract])) OR (Ischemic Stroke[Title/Abstract])) OR (Ischemic Strokes[Title/Abstract])) OR (Stroke, Ischemic[Title/Abstract])) OR (Cryptogenic Ischemic Stroke[Title/Abstract])) OR (Cryptogenic Ischemic Strokes[Title/Abstract])) OR (Ischemic Stroke, Cryptogenic[Title/Abstract])) OR (Stroke, Cryptogenic Ischemic[Title/Abstract])) OR (Cryptogenic Stroke[Title/Abstract])) OR (Cryptogenic Strokes[Title/Abstract])) OR (Stroke, Cryptogenic[Title/Abstract])) OR (Cryptogenic Embolism Stroke[Title/Abstract])) OR (Cryptogenic Embolism Strokes[Title/Abstract])) OR (Embolism Stroke, Cryptogenic[Title/Abstract])) OR (Stroke, Cryptogenic Embolism[Title/Abstract])) OR (Wake-up Stroke[Title/Abstract])) OR (Stroke, Wake-up[Title/Abstract])) OR (Wake up Stroke[Title/Abstract])) OR (Wake-up Strokes[Title/Abstract])) OR (Acute Ischemic Stroke[Title/Abstract])) OR (Acute Ischemic Strokes[Title/Abstract])) OR (Ischemic Stroke, Acute[Title/Abstract])) OR (Stroke, Acute Ischemic[Title/Abstract]))) #8 “Panax notoginseng”[Mesh] #9 ((((((((((((((((((((((((((((((((((((Panax notoginsengs[Title/Abstract]) OR (notoginsengs, Panax[Title/Abstract])) OR (fufang xueshuantong[Title/Abstract])) OR (Xueshuantong[Title/Abstract])) OR (Xue shuan tong[Title/Abstract])) OR (xueshuangtong capsule[Title/Abstract])) OR (compound xueshuantong capsule[Title/Abstract])) OR (xuesaitong soft capsule[Title/Abstract])) OR (sanqi tongshu capsule[Title/Abstract])) OR (xueshuantong injection[Title/Abstract])) OR (notoginseng saponin[Title/Abstract])) OR (total notoginsenoside[Title/Abstract])) OR (panax notoginseng saponins[Title/Abstract])) OR (radix notoginseng[Title/Abstract])) OR (radix panax notoginseng[Title/Abstract])) OR (sanqi[Title/Abstract])) OR (san qi[Title/Abstract])) OR (san-qi[Title/Abstract])) OR (panax pseudoginseng[Title/Abstract])) OR (pseudoginseng[Title/Abstract])) OR (notoginseng[Title/Abstract])) OR (pseudo ginseng[Title/Abstract])) OR (pseudo-ginseng[Title/Abstract])) OR (tianqi[Title/Abstract])) OR (tian qi[Title/Abstract])) OR (xuesetong[Title/Abstract])) OR (xue se tong[Title/Abstract])) OR (xuesaitong[Title/Abstract])) OR (xue sai tong[Title/Abstract])) OR (lulutong[Title/Abstract])) OR (lu lu tong[Title/Abstract])) OR (zheng kang nao ming[Title/Abstract])) OR (nao ming[Title/Abstract])) OR (luo tai[Title/Abstract])) OR (xin nao tai[Title/Abstract])) OR (san qi tong shu[Title/Abstract])) #10 (“Panax notoginseng”[Mesh]) OR (((((((((((((((((((((((((((((((((((((Panax notoginsengs[Title/Abstract]) OR (notoginsengs, Panax[Title/Abstract])) OR (fufang xueshuantong[Title/Abstract])) OR (Xueshuantong[Title/Abstract])) OR (Xue shuan tong[Title/Abstract])) OR (xueshuangtong capsule[Title/Abstract])) OR (compound xueshuantong capsule[Title/Abstract])) OR (xuesaitong soft capsule[Title/Abstract])) OR (sanqi tongshu capsule[Title/Abstract])) OR (xueshuantong injection[Title/Abstract])) OR (notoginseng saponin[Title/Abstract])) OR (total notoginsenoside[Title/Abstract])) OR (panax notoginseng saponins[Title/Abstract])) OR (radix notoginseng[Title/Abstract])) OR (radix panax notoginseng[Title/Abstract])) OR (sanqi[Title/Abstract])) OR (san qi[Title/Abstract])) OR (san-qi[Title/Abstract])) OR (panax pseudoginseng[Title/Abstract])) OR (pseudoginseng[Title/Abstract])) OR (notoginseng[Title/Abstract])) OR (pseudo ginseng[Title/Abstract])) OR ( pseudo-ginseng[Title/Abstract])) OR (tianqi[Title/Abstract])) OR (tian qi[Title/Abstract])) OR (xuesetong[Title/Abstract])) OR (xue se tong[Title/Abstract])) OR (xuesaitong[Title/Abstract])) OR (xue sai tong[Title/Abstract])) OR (lulutong[Title/Abstract])) OR (lu lu tong[Title/Abstract])) OR (zheng kang nao ming[Title/Abstract])) OR (nao ming[Title/Abstract])) OR (luo tai[Title/Abstract])) OR (xin nao tai[Title/Abstract])) OR (san qi tong shu[Title/Abstract]))) #11 (randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized [tiab] OR placebo [tiab] OR drug therapy [sh] OR randomly [tiab] OR trial [tiab] OR groups [tiab]) NOT (animals [mh] NOT humans [mh]) #12 (((“Stroke”[Mesh]) OR ((((((((((((((((((((((((((((Strokes[Title/Abstract]) OR (Cerebrovascular Accident[Title/Abstract])) OR (Cerebrovascular Accidents[Title/Abstract])) OR (CVA (Cerebrovascular Accident[Title/Abstract]))) OR (CVAs (Cerebrovascular Accident[Title/Abstract]))) OR (Cerebrovascular Apoplexy[Title/Abstract])) OR (Apoplexy, Cerebrovascular[Title/Abstract])) OR (Vascular Accident, Brain[Title/Abstract])) OR (Brain Vascular Accident[Title/Abstract])) OR (Brain Vascular Accidents[Title/Abstract])) OR (Vascular Accidents, Brain[Title/Abstract])) OR (Cerebrovascular Stroke[Title/Abstract])) OR (Cerebrovascular Strokes[Title/Abstract])) OR (Stroke, Cerebrovascular[Title/Abstract])) OR (Strokes, Cerebrovascular[Title/Abstract])) OR (Apoplexy[Title/Abstract])) OR (Cerebral Stroke[Title/Abstract])) OR (Cerebral Strokes[Title/Abstract])) OR (Stroke, Cerebral[Title/Abstract])) OR (Strokes, Cerebral[Title/Abstract])) OR (Stroke, Acute[Title/Abstract])) OR (Acute Stroke[Title/Abstract])) OR (Acute Strokes[Title/Abstract])) OR (Strokes, Acute[Title/Abstract])) OR (Cerebrovascular Accident, Acute[Title/Abstract])) OR (Acute Cerebrovascular Accident[Title/Abstract])) OR (Acute Cerebrovascular Accidents[Title/Abstract])) OR (Cerebrovascular Accidents, Acute[Title/Abstract]))) OR ((“Ischemic Stroke”[Mesh]) OR ((((((((((((((((((((((((Ischemic Strokes[Title/Abstract]) OR (Stroke, Ischemic[Title/Abstract])) OR (Ischemic Stroke[Title/Abstract])) OR (Ischemic Strokes[Title/Abstract])) OR (Stroke, Ischemic[Title/Abstract])) OR (Cryptogenic Ischemic Stroke[Title/Abstract])) OR (Cryptogenic Ischemic Strokes[Title/Abstract])) OR (Ischemic Stroke, Cryptogenic[Title/Abstract])) OR (Stroke, Cryptogenic Ischemic[Title/Abstract])) OR (Cryptogenic Stroke[Title/Abstract])) OR (Cryptogenic Strokes[Title/Abstract])) OR (Stroke, Cryptogenic[Title/Abstract])) OR (Cryptogenic Embolism Stroke[Title/Abstract])) OR (Cryptogenic Embolism Strokes[Title/Abstract])) OR (Embolism Stroke, Cryptogenic[Title/Abstract])) OR (Stroke, Cryptogenic Embolism[Title/Abstract])) OR (Wake-up Stroke[Title/Abstract])) OR (Stroke, Wake-up[Title/Abstract])) OR (Wake up Stroke[Title/Abstract])) OR (Wake-up Strokes[Title/Abstract])) OR (Acute Ischemic Stroke[Title/Abstract])) OR (Acute Ischemic Strokes[Title/Abstract])) OR (Ischemic Stroke, Acute[Title/Abstract])) OR (Stroke, Acute Ischemic[Title/Abstract])))) AND ((“Panax notoginseng”[Mesh]) OR (((((((((((((((((((((((((((((((((((((Panax notoginsengs[Title/Abstract]) OR (notoginsengs, Panax[Title/Abstract])) OR (fufang xueshuantong[Title/Abstract])) OR (Xueshuantong[Title/Abstract])) OR (Xue shuan tong[Title/Abstract])) OR (xueshuangtong capsule[Title/Abstract])) OR (compound xueshuantong capsule[Title/Abstract])) OR (xuesaitong soft capsule[Title/Abstract])) OR (sanqi tongshu capsule[Title/Abstract])) OR (xueshuantong injection[Title/Abstract])) OR (notoginseng saponin[Title/Abstract])) OR (total notoginsenoside[Title/Abstract])) OR (panax notoginseng saponins[Title/Abstract])) OR (radix notoginseng[Title/Abstract])) OR (radix panax notoginseng[Title/Abstract])) OR (sanqi[Title/Abstract])) OR (san qi[Title/Abstract])) OR (san-qi[Title/Abstract])) OR (panax pseudoginseng[Title/Abstract])) OR (pseudoginseng[Title/Abstract])) OR (notoginseng[Title/Abstract])) OR (pseudo ginseng[Title/Abstract])) OR ( pseudo-ginseng[Title/Abstract])) OR (tianqi[Title/Abstract])) OR (tian qi[Title/Abstract])) OR (xuesetong[Title/Abstract])) OR (xue se tong[Title/Abstract])) OR (xuesaitong[Title/Abstract])) OR (xue sai tong[Title/Abstract])) OR (lulutong[Title/Abstract])) OR (lu lu tong[Title/Abstract])) OR (zheng kang nao ming[Title/Abstract])) OR (nao ming[Title/Abstract])) OR (luo tai[Title/Abstract])) OR (xin nao tai[Title/Abstract])) OR (san qi tong shu[Title/Abstract]))))B. Embase
#1 “cerebrovascular accident”/exp #2 “strokes”: ab, ti OR “cerebrovascular accident”: ab, ti OR “cerebrovascular accidents”: ab, ti OR “cva (cerebrovascular accident)”: ab, ti OR “cvas (cerebrovascular accident)”: ab, ti OR “cerebrovascular apoplexy”: ab, ti OR “apoplexy, cerebrovascular”: ab, ti OR “vascular accident, brain”: ab, ti OR “brain vascular accident”: ab, ti OR “brain vascular accidents”: ab, ti OR “vascular accidents, brain”: ab, ti OR “stroke, cerebrovascular”: ab, ti OR “cerebrovascular strokes”: ab, ti OR “apoplexy”: ab, ti OR “strokes, cerebrovascular”: ab, ti OR “cerebral strokes”: ab, ti OR “cerebral stroke”: ab, ti OR “stroke, cerebral”: ab, ti OR “strokes, cerebral”: ab, ti OR “stroke, acute”: ab, ti OR “acute stroke”: ab, ti OR “acute strokes”: ab, ti OR “strokes, acute”: ab, ti OR “cerebrovascular accident, acute”: ab, ti OR “acute cerebrovascular accident”: ab, ti OR “acute cerebrovascular accidents”: ab, ti OR “cerebrovascular accidents, acute”: ab, ti #3 “cerebrovascular accident”/exp #4 “ischemic strokes”: ti, ab OR “stroke, ischemic”: ab, ti OR “ischemic stroke”: ab, ti OR “ischemic strokes”: ab, ti OR “stroke, ischemic”: ab, ti OR “cryptogenic ischemic stroke”: ab, ti OR “cryptogenic ischemic strokes”: ab, ti OR “ischemic stroke, cryptogenic”: ab, ti OR “stroke, cryptogenic ischemic”: ab, ti OR “scryptogenic stroke”: ab, ti OR “cryptogenic strokes”: ab, ti OR “stroke, cryptogenic”: ab, ti OR “cryptogenic embolism stroke”: ab, ti OR “cryptogenic embolism strokes”: ab, ti OR “embolism stroke, cryptogenic”: ab, ti OR “stroke, cryptogenic embolism”: ab, ti OR “wake-up stroke”: ab, ti OR “stroke, wake-up: ab, ti OR “wake up stroke”: ab, ti OR “wake-up strokes”: ab, ti OR “acute ischemic stroke”: ab, ti OR “acute ischemic strokes”: ab, ti OR “ischemic stroke, acute”: ab, ti OR “stroke, acute ischemic”: ab, ti OR #5 “panax notoginseng”/exp OR “panax notoginseng extract”/exp #6 “panax notoginsengs”: ab, ti OR notoginsengs, panax”: ab, ti OR “fufang xueshuantong”: ab, ti OR “xueshuantong”: ab, ti OR “xue shuan tong”: ab, ti OR “xueshuangtong capsule”: ab, ti OR “ompound xueshuantong capsule”: ab, ti OR “xuesaitong soft capsule”: ab, ti OR “tsanqi tongshu capsule”: ab, ti OR “xueshuantong injection”: ab, ti OR “notoginseng saponin”: ab, ti OR “total notoginsenoside”: ab, ti OR “panax notoginseng saponins”: ab, ti OR “radix notoginseng”: ab, ti OR “radix panax notoginseng”: ab, ti OR “sanqi”: ab, ti OR “san qi”: ab, ti OR “san-qi”: ab, ti OR “panax pseudoginseng”: ab, ti OR “pseudoginseng”: ab, ti OR “notoginseng”: ab, ti OR “pseudo ginseng”: ab, ti OR “pseudo-ginseng”: ab, ti OR “tianqi”: ab, ti OR “tian qi”: ab, ti OR “xuesetong”: ab, ti OR “xue se tong”: ab, ti OR “xuesaitong”: ab, ti OR “xue sai tong”: ab, ti OR “lulutong”: ab, ti OR “lu lu tong”: ab, ti OR “zheng kang nao ming”: ab, ti OR “nao ming”: ab, ti OR “luo tai”: ab, ti OR “luotai”: ab, ti OR “xin nao tai”: ab, ti OR “xinnaotai”: ab, ti OR “naoming”: ab, ti OR “san qi tong shu”: ab, ti OR “sanqitongshu”: ab, ti OR #7 “crossover procedure”: de OR “double-blind procedure”: de OR “randomized controlled trial”: de OR “single-blind procedure”: de OR random: de, ab, ti OR factorial: de, ab, ti OR crossover: de, ab, ti OR ((cross NEXT/1over): de, ab, ti) OR placebo: de, ab, ti OR ((doublNEAR/1 blind): de, ab, ti) OR ((singl NEAR/1 blind): de, ab, ti) OR assign: de, ab, ti OR allocat: de, ab, ti OR volunteer: de, ab, ti #8 #1 OR #2 OR #3 OR #4 #9 #5 OR #6 #10 #8 AND #9 AND #10C. Cochrane Library
#1 MeSH descriptor: [Stroke] explode all trees #2 (Strokes): ti, ab, kw OR (Cerebrovascular Accident): ti, ab, kw OR (Cerebrovascular Accidents): ti, ab, kw OR (CVA (cerebrovascular accident)): ti, ab, kw OR (CVAs (cerebrovascular accident)): ti, ab, kw OR (cerebrovascular apoplexy): ti, ab, kw OR (apoplexy, cerebrovascular): ti, ab, kw OR (vascular accident, brain): ti, ab, kw OR (brain vascular accident): ti, ab, kw OR (brain vascular accidents): ti, ab, kw OR (vascular accidents, brain): ti, ab, kw OR (cerebrovascular stroke): ti, ab, kw OR (cerebrovascular strokes): ti, ab, kw OR (stroke, cerebrovascular): ti, ab, kw OR (strokes, cerebrovascular): ti, ab, kw OR (apoplexy): ti, ab, kw OR (cerebral stroke): ti, ab, kw OR (cerebral strokes): ti, ab, kw OR (stroke, cerebral): ti, ab, kw OR (strokes, cerebral): ti, ab, kw OR (stroke, acute): ti, ab, kw OR (acute stroke): ti, ab, kw OR (acute strokes): ti, ab, kw OR (strokes, acute): ti, ab, kw OR (cerebrovascular accident, acute): ti, ab, kw OR (acute cerebrovascular accident): ti, ab, kw OR (acute cerebrovascular accidents): ti, ab, kw OR (cerebrovascular accidents, acute): ti, ab, kw OR (ischemic stroke): ti, ab, kw OR (ischemic strokes): ti, ab, kw OR (stroke, ischemic): ti, ab, kw OR (ischemic stroke): ti, ab, kw OR (ischemic strokes): ti, ab, kw OR (stroke, ischemic): ti, ab, kw OR (cryptogenic ischemic stroke): ti, ab, kw OR (cryptogenic ischemic strokes): ti, ab, kw OR (ischemic stroke, cryptogenic): ti, ab, kw OR (stroke, cryptogenic ischemic): ti, ab, kw OR (cryptogenic stroke): ti, ab, kw OR (cryptogenic strokes): ti, ab, kw OR (stroke, cryptogenic): ti, ab, kw OR (cryptogenic embolism stroke): ti, ab, kw OR (cryptogenic embolism strokes): ti, ab, kw OR (embolism stroke, cryptogenic): ti, ab, kw OR (stroke, cryptogenic embolism): ti, ab, kw OR (wake-up stroke): ti, ab, kw OR (stroke, wake-up): ti, ab, kw OR (wake up stroke): ti, ab, kw OR (wake-up strokes): ti, ab, kw OR (acute ischemic stroke): ti, ab, kw OR (acute ischemic strokes): ti, ab, kw OR (ischemic stroke, acute): ti, ab, kw OR (stroke, acute ischemic): ti, ab, kw #3 MeSH descriptor: [Ischemic Stroke] explode all trees #4 (notoginsengs, panax): ti, ab, kw OR (panax notoginsengs): ti, ab, kw OR (panax notoginseng extract): ti, ab, kw OR (xueshuantong): ti, ab, kw OR (fufang xueshuantong): ti, ab, kw OR (xue shuan tong): ti, ab, kw OR (xueshuangtong capsule): ti, ab, kw OR (compound xueshuantong capsule): ti, ab, kw OR (xuesaitong soft capsule): ti, ab, kw OR (sanqi tongshu capsule): ti, ab, kw OR (xueshuantong injection): ti, ab, kw OR (notoginseng saponin): ti, ab, kw OR (total notoginsenoside): ti, ab, kw OR (panax notoginseng saponins): ti, ab, kw OR (radix notoginseng): ti, ab, kw OR (radix panax notoginseng): ti, ab, kw OR (sanqi): ti, ab, kw OR (san qi): ti, ab, kw OR (san-qi): ti, ab, kw OR (panax pseudoginseng): ti, ab, kw OR (pseudoginseng): ti, ab, kw OR (notoginseng): ti, ab, kw OR (pseudo ginseng): ti, ab, kw OR (pseudo-ginseng): ti, ab, kw OR (tianqi): ti, ab, kw OR (tian qi): ti, ab, kw OR (xuesetong): ti, ab, kw OR (xue se tong): ti, ab, kw OR (xuesaitong): ti, ab, kw OR (xue sai tong): ti, ab, kw OR (lulutong): ti, ab, kw OR (lu lu tong): ti, ab, kw OR (zheng kang nao ming): ti, ab, kw OR (nao ming): ti, ab, kw OR (luo tai): ti, ab, kw OR (xin nao tai): ti, ab, kw OR (san qi tong shu): ti, ab, kw #5 #1 OR #2 OR #3 #6 #4 AND #5D. Web of Science
#1 TS = (stroke OR stroke OR cerebrovascular accident OR cerebrovascular accident OR CVA (cerebrovascular accident) OR CVAs (cerebrovascular accident) OR cerebrovascular apoplexy OR apoplexy, cerebrovascular OR vascular accident, brain OR brain vascular accident OR brain vascular accidents OR vascular accidents, brain OR cerebrovascular stroke OR cerebrovascular strokes OR stroke, cerebrovascular OR strokes, cerebrovascular OR apoplexy OR cerebral stroke OR cerebral strokes OR stroke, cerebral OR strokes, cerebral OR stroke, acute OR acute stroke OR acute strokes OR strokes, acute OR cerebrovascular accident, acute OR acute cerebrovascular accident OR acute cerebrovascular accidents OR cerebrovascular accidents, acute OR ischemic stroke OR ischemic strokes OR stroke, ischemic OR ischemic stroke OR ischemic strokes OR stroke, ischemic OR cryptogenic ischemic stroke OR cryptogenic ischemic strokes OR ischemic stroke, cryptogenic OR stroke, cryptogenic ischemic OR cryptogenic stroke OR cryptogenic strokes OR stroke, cryptogenic OR cryptogenic embolism stroke OR cryptogenic embolism strokes OR embolism stroke, cryptogenic OR stroke, cryptogenic embolism OR wake-up stroke OR stroke, wake-up OR wake up stroke OR wake-up strokes OR acute ischemic stroke OR acute ischemic strokes OR ischemic stroke, acute OR stroke, acute ischemic) #2 TS = (panax notoginseng OR panax notoginsengs OR panax notoginseng extract OR notoginsengs, panax OR fufang xueshuantong OR xueshuantong OR xue shuan tong OR xueshuangtong capsule OR compound xueshuantong capsule OR xuesaitong soft capsule OR sanqi tongshu capsule OR xueshuantong injection OR notoginseng saponin OR total notoginsenoside OR panax notoginseng saponins OR radix notoginseng OR radix panax notoginseng OR sanqi OR san qi OR san-qi OR panax pseudoginseng OR pseudoginseng OR notoginseng OR pseudo ginseng OR pseudo-ginseng OR tianqi OR tian qi OR xuesetong OR xue se tong OR xuesaitong OR xue sai tong OR lulutong OR lu lu tong OR zheng kang nao ming OR nao ming OR luo tai OR xin nao tai OR san qi tong shu) #3 TS = clinical trial OR TS = research design OR TS = comparative stud OR TS = evaluation stud OR TS = controlled trial OR TS = follow-up stud OR TS = prospective stud OR TS = random OR TS = placebo OR TS = (single blind) OR TS = (double blind) #4 #1 AND #2 AND #3Abbreviations
| PNS: | Panax notoginseng saponins |
| RCT: | Randomized controlled trials |
| RR: | Relative risk |
| CI: | Confidence interval |
| SMD: | Standard mean difference |
| WM: | Western medicine |
| TAU: | Treatment as usual |
| XC: | Xueshuantong capsule |
| XSC: | Xuesaitong soft capsule |
| STC: | Sanqi Tongshu capsule |
| CXC: | Compound Xueshuantong capsule |
| TCM: | Traditional Chinese Medicine |
| NIHSS: | National Institutes of Health Stroke Scale |
| PTS: | Panaxtriol saponins |
| BMP: | Mean blood pressure |
| CVR: | Cerebrovascular resistance. |
Data Availability
Some or all data generated or analyzed during this study are included in this published article or in the data repositories listed in references.
Disclosure
The authors affirm that the work submitted for publication is original and has not been published other than as an abstract or preprint in any language or format and has not been submitted elsewhere for print or electronic publication consideration. The authors affirm that each person listed as authors participated in the work in a substantive manner, in accordance with ICMJE authorship guidelines, and is prepared to take public responsibility for it. All authors consent to the investigation of any improprieties that may be alleged regarding the work. Each author further releases and holds harmless the Endocrine Society from any claim or liability that may arise there from.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
Authors’ Contributions
Peiyu Guan, principal author with full access to all the data in the study, takes responsibility for the accuracy of the data analysis, and the integrity of the data. Peiyu Guan, Youhua Xu, and Dingkun Gui contributed to the conception and design. Peiyu Guan contributed to data acquisition and interpretation. Peiyu Guan contributed to draft of the manuscript. Youhua Xu and Dingkun Gui contributed to revision of the article and final approval.
Acknowledgments
The work was supported by the Science and Technology Development Fund of Macao (FDCT: 0055/2019/AMJ).
Supplementary Materials
Supplementary PRISMA-2020 checklist [20]. (Supplementary Materials)