Search

BackgroundStroke is a serious health issue that can result in death or disability, leading to a significant economic strain on society and families. A growing number of studies have shown that the Naoshuantong capsule (NSTC) is beneficial as a treatment for ischemic stroke (IS) in recent years. Our study aims to provide an update on the safety and efficacy of the NSTC in IS patients.MethodsWe thoroughly searched eight databases to identify suitable randomized controlled trials (RCTs) assessing the effectiveness of the NSTC in the treatment of IS. The National Institute of Health Stroke Scale (NIHSS) for an acute period and modified Rankin Scale (mRS) at 3 months for a non-acute period were considered the primary outcome, and secondary outcomes included the NIHSS for a non-acute period, mRS, Barthel Index (BI), modified Barthel Index (MBI), Stroke-specific Quality of life (SS-QOL), and the recurrence rate of cerebrovascular events. Subsequently, its quality was assessed using the Cochrane risk assessment scale. Statistical analysis was conducted using RevMan 5.3 and Stata 14.0.ResultsA total of 27 RCTs were included, which involved 3,139 patients. The results showed that the NSTC improved neurological function not only in the acute period (MD = −2.53; 95% CI: −2.91, −2.15; p < 0.00001) but also in the non-acute period (MD = −3.70; 95% CI: −5.82, −1.58; p = 0.0006) and improved the long-term functional outcomes with lower mRS scores (MD = −0.68; 95% CI: −1.09, −0.26; p = 0.001). At the same time, the NSTC decreased the risk of cerebrovascular disease recurrence (RR = 0.43; 95% CI: 0.27, 0.70; p = 0.0006) and increased the quality of life in the acute period (MD = 23.88; 95% CI: 16.63, 31.13; p < 0.00001). Significant disparities in the incidence of adverse events between the NSTC and control groups were not observed. The certainty of evidence was estimated as moderate to very low.ConclusionThe NSTC emerges as a potentially efficacious and safe treatment option for IS. NSTC could improve neurological function in different period of IS, and it has certain clinical value in secondary prevention. As a result of the poor quality and heterogeneity of the included trials, larger and standardized RCTs are needed to validate NSTC in IS treatment.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=482981, identifier CRD42023482981.

Background Randomized controlled trials have demonstrated that Songling Xuemaikang capsule (SXC) is effective in blood pressure (BP) lowering for essential hypertension. However, the effectiveness of SXC in real-world clinical practice remains unknown. We aimed to investigate whether the BP-lowering effectiveness of SXC in the real-world practice setting is comparable to the efficacy of the intervention in a randomized controlled trial. Methods We included 1325 patients treated with SXC monotherapy from a real-world registry and 300 from the SXC-BP trial. A propensity score matching (PSM) approach was used to select participants from the two cohorts. The primary outcome was a change in the office of BP from baseline to 8 weeks. Results After PSM, there were 552 patients for the comparative analysis. Clinically meaningful BP reductions were observed both in the real world and in the RCT cohorts after 8-week SXC treatment. The 8-week systolic/diastolic BP was 129.50/81.33 mm Hg vs. 134.97/84.14 mm Hg in the real-world population and the RCT population, respectively. The changes in systolic BP (15.82 ± 10.71 vs. 10.48 ± 10.24; P

BackgroundMoyamoya disease (MMD) is a leading cause of stroke in children and young adults, whereas no specific drugs are available. Antiplatelet therapy (APT) has been considered a promising treatment option, but its effectiveness remains controversial. Therefore, we aimed to comprehensively evaluate the benefits and risks of APT for MMD.MethodsWe systematically searched PubMed, Embase, and Cochrane Library electronic databases from their inception to 30 June 2022 and conducted a systematic review. All-cause mortality was taken as the primary outcome.ResultsNine studies that enrolled 16,186 patients with MMD were included. The results from a single study showed that APT was associated with lower mortality [hazard ratio (HR) = 0.60; 95% confidence interval (CI) (0.50–0.71); p < 0.01] and improved bypass patency after surgical revascularization [HR = 1.57; 95% CI (1.106–2.235); p < 0.05]. The results of the meta-analysis showed that APT reduced the risk of hemorrhagic stroke [HR = 0.47; 95% CI (0.24–0.94); p < 0.05] but neither reduced the risk of ischemic stroke [HR = 0.80; 95% CI (0.33–1.94); p = 0.63] nor increased the proportion of independent patients [RR = 1.02; 95% CI (0.97–1.06); p = 0.47].ConclusionCurrent evidence showed that APT was associated with a reduced risk of hemorrhagic stroke in MMD patients but did not reduce the risk of ischemic stroke or increase the proportion of independent patients. There was insufficient evidence about the benefit of APT on survival and postoperative bypass patency after surgical revascularization. However, the results should be interpreted cautiously because of the limited number of studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/.

Background: Deciphering the biological basis of traditional Chinese medicine (TCM) syndromes in complex diseases is challenging. Rapid advances in multi-omics approaches provide new opportunities to unveil the biological basis of TCM syndromes. We intend to summarize the latest significant progress and highlight the crucial value of applying multi-omics approaches to reveal TCM syndromes of stroke in a new horizon.Methods: We systematically searched PubMed, EMBASE, Web of Science Core Collection (WOSCC), Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang database and China Biology Medicine Database (SinoMed) for relevant studies from their inception to 31 March 2022, and conducted a comprehensive systematic review (PROSPERO registration number: CRD42021285922).Results: A total of 43 relevant studies were included in the final systematic review, genomics, transcriptomics, proteomics, and metabolomics were all involved. Some gene polymorphisms, differential lncRNAs, mRNAs, miRNAs, proteins, and metabolites may be associated with TCM syndromes of stroke. In addition, some studies conducted a preliminary exploration on the different diseases with the same TCM syndrome. The results showed that thioredoxin-dependent peroxidase reductase may be the specific marker protein of Liver-yang transforming into wind syndrome, and the network formed by mir-146b-5p, -199a-5p, and 23 targeted mRNAs may be the biomarker of Blood-stasis syndrome.Conclusion: Multi-omics technologies have served as powerful tools to investigate the complexity of TCM syndromes and may hold the promise of promoting the modernization of TCM as well as personalized medicine of TCM in stroke.

Background: Due to limited time windows and technical requirements, only a small percentage of patients can receive reperfusion therapy for acute ischemic stroke (AIS). Previous studies have shown that LongShengZhi (LSZ) capsule can improve neurological outcomes in patients after AIS, yet those results have not been finally verified through rigorous randomized controlled trials. Thus, this trial was designed to further clarify the efficacy and safety of LSZ capsule for patients with AIS.Methods: LSZ capsule on Functional Recovery after Acute Ischemic Stroke (LONGAN) trial is a prospective, multicenter, randomized, placebo-controlled, double-blind, parallel-group, superiority trial that enrolls patients from stroke and rehabilitation units in China. We will enroll 1,376 patients aged 18 years or older with AIS within 7 days of symptom onset and a National Institute of Health Stroke Scale (NIHSS) score of 4–15. Eligible patients will be randomized to receive either 2 g LSZ capsules three times a day or placebo LSZ capsules for 90 days. The primary outcome is the proportion of patients with favorable outcomes, as measured by the modified Rankin Scale (mRS) 90 days after randomization. The main safety outcome is the proportion of severe adverse events.Conclusion: This study will be the first randomized, double-blind trial to evaluate the efficacy and safety of LSZ capsule in patients with AIS. In order to improve the transparency and reproducibility of the trial, the data will be analyzed in accordance with this pre-specified plan for statistical analysis to reduce bias due to selective analysis and reporting. This trial aims to provide high-quality evidence for the efficacy and safety of LSZ capsule for AIS.

Background: Edaravone alleviates neurological deficits among patients with intracerebral hemorrhage; however, its effects on mortality and long-term functional outcomes remain unknown.Objective: To assess clinical outcomes associated with edaravone initiated within 7 days of symptoms onset in intracerebral hemorrhage.Methods: We systematically searched PubMed, Embase, Cochrane Library, CiNii, China National Knowledge Infrastructure, Chinese VIP information, Wanfang Data, and SinoMed for relevant randomized controlled trials from their inception to 1 May 2021 and conducted a comprehensive systematic review and meta-analysis (PROSPERO registration number: CRD42019147801). All-cause mortality and long-term functional outcomes were taken as the primary outcomes.Results: A total of 38 randomized controlled trials including 3,454 participants with acute intracerebral hemorrhage were included. The selected articles were of poor quality. Meta-analysis revealed that edaravone could not reduce all-cause mortality [relative risk (RR) = 0.51; 95% confidence interval (CI) (0.11–2.32); p = 0.38]. No studies reported on long-term functional outcomes in those trials. In addition, edaravone alleviated neurological deficits [mean difference (MD) = −5.44; 95% CI (−6.44 to −4.44); p

Background: Acute ischemic stroke (AIS) is a common cause of death and long-term disability worldwide. Recent trials of platelet-activating factor receptor antagonists (PAFRA) appeared to indicate that they could play a neuroprotective role in the treatment of AIS; therefore, we conducted a systematic literature review to evaluate the clinical efficacy and safety of PAFRA in patients with AIS.Methods: A systematic literature search was performed in seven electronic databases from inception to 11 March 2022. All randomized controlled trials (RCTs) in which patients were treated with PAFRA strategies within 7 days of stroke onset were included. Modified Rankin Scale (mRS) was selected as the primary outcome of this systematic review. The methodological quality of included studies was assessed based on the Cochrane Collaborations tool. The review protocol was previously registered (PROSPERO CRD42020182075).Results: Fifteen RCTs comprising a total of 3,907 participants were included in this study. The PAFRA-related compounds included natural preparations of terpenoids, flavonoids, and saponins, namely, ginkgo endoterpene diester meglumine (GEDM, seven RCTs), ginkgo biloba dropping pill (GBDP, one RCT), ginkgolide injection (GDI, four RCTs), hesperidin (HES, one RCT), ginsenoside Rd injection (GSRI, one RCT), and hydroxysafflor yellow A (HSYA, one RCT). All studies were conducted in China between 2017 and 2021, employing a two-arm parallel design with sample sizes ranging from 40 to 1,113. Eight studies (53.3%) provided no information on their method of randomization, and only two studies (13.3%) utilized the double-blind design. Treatment was associated with improved clinical outcomes for (1) GEDM, GDI, and GBDP in patients treated with conventional treatment (CM) [GEDM + CM for AIS on mRS: MDmRS = −0.42, 95% CI (−0.47, −0.37), five trials, p < 0.00001; GEDM + CM for AIS on NIHSS: MDNIHSS = −1.02, 95% CI (−1.51, −0.52), four trials, p < 0.0001]; (2) GEDM and GDI in patients treated with neuroprotective agent (NPA) [GEDM + NPA + CM for AIS on mRS: MDmRS = −0.40, 95% CI (−0.54, −0.26), p < 0.00001; GEDM + NPA + CM for AIS on NIHSS: MDNIHSS = −3.93, 95%CI (−7.72, −0.14), p = 0.04]; (3) GBDP in patients treated with CM; (4) GDI and GSRI in patients treated with IV rt-PA therapy (IVT); and (5) HSYA in patients compared with Dengzhan Xixin injection (DZXXI). No access to improved clinical outcome was associated with HES in patients treated with IVT. Seven RCTs reported adverse events (AEs) but found that taking PAFRA-related preparations was not associated with an increased incidence of AEs.Conclusions: This systematic review not only makes an important contribution to the existing body of current evidence but also lays a well-conducted basis for providing opinions and recommendation on the evaluation of PAFRA-based medicine, which could also highlight the need for well-designed clinical trials of PAFRA for AIS to increase the quality of available evidence. Further research is required, using standardized functional outcome measures for AIS, adequate blinding and suitable comparator groups reflecting current best practice.

Background: As the only traditional Chinese medicine injection approved by the China Food and Drug Administration for use as stroke first aid in ambulances, Xingnaojing Injection (XNJI) has been widely used in cases of both acute ischemic stroke (IS) and intracerebral hemorrhage (ICH). However, there is no robust clinical evidence regarding the efficacy and safety of the early use of XNJI during stroke first aid. The main purpose of this trial is to observe whether XNJI, intravenously administered within 24 h of onset in the prehospital ambulance setting, protects against early neurological deterioration (END) on the third day of onset in patients with acute stroke.Methods: The Trial of a prehospital intervention with traditional Chinese medicine for acute stroke (TRACE) is a Mixed-Methods research (MMR) study that involves a combination of quantitative and qualitative research. The quantitative research part of this project is a prospective, multicenter, observational, clinical registry study, for which we aimed to recruit 1,000 patients with acute stroke (IS and ICH). Based on our observation of whether XNJI was intravenously administered within 24 h of onset in the prehospital ambulance setting, patients with acute stroke will be divided into two groups: the exposure group comprising patients who were intravenously administered XNJI and the nonexposure group comprising patients who were not. The primary outcome is early neurological deterioration (END) on the third day of onset defined as an increase of 2 or more points in the National Institute of Health Stroke Scale score between baseline and day 3. In addition, based on the aforementioned quantitative research, qualitative research will be conducted by interviewing emergency doctors about their knowledge and attitude regarding XNJI used for stroke first aid.Discussion: The results of the TRACE study will provide preliminary evidence for the relationship between XNJI used within 24 h of onset and the presence of END on the third day after stroke onset; it will aid in improving the current knowledge regarding the early use of XNJI for stroke first aid.Clinical Trial Registration:clinicaltrials.gov, identifier NCT04275349

Cerebral small vessel disease (CSVD) is the most common chronic vascular disease involving the whole brain. Great progress has been made in clinical imaging, pathological mechanism, and treatment of CSVD, but many problems remain. Clarifying the current research dilemmas and future development direction of CSVD can provide new ideas for both basic and clinical research. In this review, the risk factors, biological markers, pathological mechanisms, and the treatment of CSVD will be systematically illustrated to provide the current research status of CSVD. The future development direction of CSVD will be elucidated by summarizing the research difficulties.

Background: Given the complexity of stroke treatment and the current widespread use of traditional Chinese medicine (TCM) in the absence of robust, large, long-term effectiveness and safety studies, and the lack of nationwide epidemiology and clinical characteristics of patients with stroke receiving TCM treatment, the acquisition of data from longitudinal cohorts is essential. We intend to generate the major clinical characteristics of patients with stroke who receive TCM treatment and to investigate the effectiveness and safety of TCM in the Chinese population.Methods: The China Stroke Registry for Patients with Traditional Chinese Medicine (CASES-TCM) study is a prospective, multicenter, observational disease registry aiming to register 20,000 hospitalized patients. Eligible adult patients with clearly diagnosed acute ischemic stroke or intracerebral hemorrhage within 7 days of symptom onset will be consecutively registered from 126 participating sites across China. Baseline data will be recorded, and all patients will be regularly followed up at 3, 6, 12, and 24 months after stroke onset. Collected data will be entered into a web-based system with high-level data security. The primary outcomes include the distribution of scores on the modified Rankin Scale at the 3-months follow-up, and recurrent stroke events within the 12-months follow-up.Conclusion: To our knowledge, the CASES-TCM study is the first and largest nationwide registry to document comprehensive data on TCM treatment in patients with acute stroke. The findings of this study will be valuable to improve our knowledge about TCM treatment for patients with stroke and its subsequent outcomes in the actual clinical setting, consequently facilitating and standardizing the optimization of individualized interventions with TCM for stroke prevention and treatment in China.Study registration: This study was registered with Clinicaltrials.gov (URL: https://clinicaltrials.gov/, Unique identifier: NCT04921397).

Guizhi-Fuling capsule (GZFLC), originated from a classical traditional Chinese herbal formula Guizhi-Fuling Wan, has been clinically used for primary dysmenorrhea in China. Nonetheless, the underlying pharmacological mechanisms of GZFLC remain unclear. The integration of computational and experimental methods of network pharmacology might be a promising way to decipher the mechanisms. In this study, the target profiles of 51 representative compounds of GZFLC were first predicted by a high-accuracy algorithm, drugCIPHER-CS, and the network target of GZFLC was identified. Then, potential functional modules of GZFLC on primary dysmenorrhea were investigated using functional enrichment analysis. Potential bioactive compounds were recognized by hierarchical clustering analysis of GZFLC compounds and first-line anti-dysmenorrhea drugs. Furthermore, the potential anti-dysmenorrhea mechanisms of GZFLC were verified through enzyme activity assays and immunofluorescence tests. Moreover, effects of GZFLC on primary dysmenorrhea were evaluated in oxytocin-induced dysmenorrhea murine model. In the network target analysis, GZFLC may act on five functional modules of pain, inflammation, endocrine, blood circulation and energy metabolism. Integrating computational and experimental approaches, we found that GZFLC significantly inhibited the writhing response and reduced the degree of uterine lesions in oxytocin-induced dysmenorrhea murine model. Furthermore, GZFLC may partially alleviate primary dysmenorrhea by inhibiting cyclooxygenase 2 (COX2) and downregulating MAPK signaling pathway. Consequently, GZFLC presented pain relief and sustained benefits for primary dysmenorrhea. This study could provide a scientific approach for deciphering pharmacological mechanisms of herbal formulae through network pharmacology.

Introduction With the threat of a worldwide pandemic of COVID-19, it is important to identify the prognostic factors for critical conditions among patients with non-critical COVID-19. Prognostic factors and models may assist front-line clinicians in rapid identification of high-risk patients, early management of modifiable factors, appropriate triaging and optimising the use of limited healthcare resources. We aim to systematically assess the clinical, laboratory and imaging predictors as well as prediction models for severe or critical illness and mortality in patients with COVID-19.Methods and analysis All peer-reviewed and preprint primary articles with a longitudinal design that focused on prognostic factors or models for critical illness and mortality related to COVID-19 will be eligible for inclusion. A systematic search of 11 databases including PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, VIP, Wanfang Data, SinoMed, bioRxiv, Arxiv and MedRxiv will be conducted. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction will be performed using the modified version of the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist and quality will be evaluated using the Newcastle-Ottawa Scale and the Quality In Prognosis Studies tool. The association between prognostic factors and outcomes of interest will be synthesised and a meta-analysis will be conducted with three or more studies reporting a particular factor in a consistent manner.Ethics and dissemination Ethical approval was not required for this systematic review. We will disseminate our findings through publication in a peer-reviewed journal.PROSPERO registration number CRD 42020178798.

Abstract Background Xingnaojing injection (XNJ) is widely used for the treatment of stroke in China. However, there is currently a lack of high-quality evidence of its efficacy for acute ischemic stroke. The main objective of this study is to determine whether the addition of XNJ to standard care improves the 3-month functional outcome in patients with acute ischemic stroke (AIS). Methods/design The XMAS study is a multicenter, prospective, randomized controlled, open-label trial with a blinded endpoints design. A total of 720 patients will be randomly allocated to either the intervention or the control group in a 1:1 ratio. The intervention group receives XNJ combined with standard care, and the control group receives standard care alone. XNJ will be administered intravenously every 12 h for 10 days. The primary outcome is the proportion of patients who are independent at 3 months after stroke onset defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes include early neurological deterioration at 48 h, the change in National Institutes of Health Stroke Scale score, patient-reported outcome, symptomatic intracranial hemorrhage at 10 days, the Barthel Index score, deaths from any cause and cardiovascular events at 3 months. Discussion The results of this trial will provide critical evidence for XNJ in the treatment of AIS as a complementary approach that can be initiated after reperfusion therapy or when the AIS is not eligible for thrombolytic treatment. Trial registration Clinical Trials.gov, ID: NCT02728180 . Registered on 28 March 2016.

Summary: Intestinal-type gastric cancer is preceded by premalignant lesions, including chronic atrophic gastritis and intestinal metaplasia. In this study, we constructed a single-cell atlas for 32,332 high-quality cells from gastric antral mucosa biopsies of patients spanning a cascade of gastric premalignant lesions and early gastric cancer (EGC) using single-cell RNA sequencing. We then constructed a single-cell network underlying cellular and molecular characteristics of gastric epithelial cells across different lesions. We found that gland mucous cells tended to acquire an intestinal-like stem cell phenotype during metaplasia, and we identified OR51E1 as a marker for unique endocrine cells in the early-malignant lesion. We also found that HES6 might mark the pre-goblet cell cluster, potentially aiding identification of metaplasia at the early stage. Finally, we identified a panel of EGC-specific signatures, with clinical implications for the precise diagnosis of EGC. Our study offers unparalleled insights into the human gastric cellulome in premalignant and early-malignant lesions. : Zhang et al. conduct a single-cell transcriptomic study on gastric antral biopsies from patients across premalignant lesions and early gastric cancer. They construct the single-cell network for epithelial cells across lesions and dissect the molecular characteristics for representative cell types in each lesion. Keywords: single-cell, stomach, premalignant lesions, early gastric cancer, network