Chinese Herbal Medicine Xingnaojing Injection for Acute Ischemic Stroke: An Overview of Systematic Reviews and Meta-Analyses.

Background: Xingnaojing injection (XNJ) is the only Chinese herbal injection approved for both intracerebral hemorrhage and ischemic stroke (IS) first-aid on ambulances in China; many systematic reviews (SRs) and meta-analyses (MAs) of XNJ on stroke have been published. The purpose of this research was to evaluate and summarize the current evidence on XNJ for IS. Methods: A comprehensive search was conducted for SRs and MAs of XNJ on IS in seven databases up to January 1, 2021. Two authors independently identified SRs and MAs, extracted data, assessed the quality of the included SRs and MAs using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and assessed quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results: A total of 10 SRs met the inclusion criteria. The quality of included SRs using AMSTAR 2 was critically low as the critical items were poorly reported. Only 10% of SRs reported 50% of the 16 items, while the remaining 90% SRs reported just less than half of the items on AMSTAR 2. For GRADE, 7 (35%) of outcomes had low-quality evidence, 10 (50%) with very low, and 3 (15%) with moderate quality evidence. Very low to low quality of evidence indicated XNJ plus conventional therapy (CT) alleviated the neurological deficits of acute IS. Moderate-quality evidence showed XNJ plus CT reduced mortality when compared to Danshen injection plus CT, and very low-quality evidence showed XNJ plus CT could not improve the degree of coma, while low-quality evidence indicated the opposite. Mild adverse events in the CT group were less than those in the XNJ plus CT group, and there were no serious adverse events, but there was no statistical difference between the two groups. The included 10 SRs indicated that XNJ was used for acute IS, but only four SRs (40%) reported the course of disease. Conclusion: XNJ appears to be effective and safe for acute IS in improving the neurological deficits, but the evidence is not robust enough. However, whether administering XNJ immediately after or within 24 h of IS is best remains unknown due to the lack of data. Well-designed large-scale randomized controlled trials with measurable outcomes are required in future studies.

Radix Sophorae flavescentis versus no intervention or placebo for chronic hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) infection, a liver disease caused by hepatitis B virus, may lead to serious complications such as cirrhosis and hepatocellular carcinoma. People with HBV infection may have co-infections including HIV and other hepatitis viruses (hepatitis C or D), and co-infection may increase the risk of all-cause mortality. Chronic HBV infection increases morbidity and psychological stress and is an economic burden on people with chronic hepatitis B and their families. Radix Sophorae flavescentis, an herbal medicine, is administered most often in combination with other drugs or herbs. It is believed that it decreases discomfort and prevents replication of the virus in people with chronic hepatitis B. However, the benefits and harms of Radix Sophorae flavescentis for patient-centred outcomes are not known, and its wide usage has never been established with rigorous review methodology. OBJECTIVES: To assess the benefits and harms of Radix Sophorae flavescentis versus placebo or no intervention in people with chronic hepatitis B. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and SinoMed. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry for ongoing or unpublished trials. We conducted the last search in December 2018. SELECTION CRITERIA: We included randomised clinical trials, irrespective of publication status, language, or blinding, comparing Radix Sophorae flavescentis versus no intervention or placebo in people with chronic hepatitis B. We excluded polyherbal blends containing Radix Sophorae flavescentis. We allowed co-interventions when the co-interventions were administered equally to all intervention groups. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. Review authors in pairs retrieved data from individual published reports and after correspondence with investigators. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered 'not to be serious'. We presented meta-analysed results as risk ratios (RRs) with 95% confidence intervals (CIs). We assessed risk of bias using domains with pre-defined definitions. We conducted Trial Sequential Analyses to control the risk of random errors. We used GRADE methodology to evaluate our certainty in the evidence (i.e. "the extent of our confidence that the estimates of the effect are correct or are adequate to support a particular decision or recommendation"). MAIN RESULTS: We included 35 randomised clinical trials with 3556 participants. One trial compared Radix Sophorae flavescentis with placebo; the remaining 34 trials compared effects of Radix Sophorae flavescentis in addition to a co-intervention versus the same co-intervention. The included trials assessed heterogenous forms and ways of administering Radix Sophorae flavescentis (e.g. oral capsules, oral tablets, intravenous infusion, intramuscular injection, acupoint (a specifically chosen site of acupuncture) injection) with treatment duration of 1 to 24 months. Two of the trials included children up to 14 years old. Participants in two trials had cirrhosis in addition to chronic hepatitis B. All trials were assessed at high risk of bias, and certainty of the evidence for all outcomes was very low.Only one of the 35 trials assessed mortality; no deaths occurred. Ten trials assessed serious adverse events; no serious adverse events occurred. None of the trials reported health-related quality of life, hepatitis B-related mortality, or morbidity. Adverse events considered 'not to be serious' was an outcome in 19 trials; nine of these trials had zero events in both groups. Radix Sophorae flavescentis versus placebo or no intervention showed no difference in effects on adverse events considered 'not to be serious' (RR 1.10, 95% CI 0.76 to 1.59; I² = 49%; 10 trials, 1050 participants). Radix Sophorae flavescentis showed a reduction in the proportion of participants with detectable HBV-DNA (RR 0.61, 95% CI 0.55 to 0.68; I² = 56%; 29 trials, 2914 participants) and in the proportion of participants with detectable HBeAg (hepatitis B e-antigen) (RR 0.71, 95% CI 0.66 to 0.76; I² = 19%; 20 trials, 2129 participants).Seven of the 35 randomised clinical trials received academic funding from government or hospital. Four trials received no funding. The remaining 24 trials provided no information on funding.Additionally, 432 trials lacked the methodological information needed to ensure inclusion of these trials in our review. AUTHORS' CONCLUSIONS: The included trials lacked data on health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. The effects of Radix Sophorae flavescentis on all-cause mortality and on the proportion of participants with serious adverse events and adverse events considered 'not to be serious' remain unclear. We advise caution in interpreting results showing that Radix Sophorae flavescentis reduced the proportion of people with detectable HBV-DNA and detectable HBeAg because the trials reporting on these outcomes are at high risk of bias and both outcomes are non-validated surrogate outcomes. We were unable to obtain information on the design and conduct of a large number of trials; therefore, we were deterred from including them in our review. Undisclosed funding may influence trial results and may lead to poor trial design. Given the wide usage of Radix Sophorae flavescentis, we need large, unbiased, high-quality placebo-controlled randomised trials in which patient-centred outcomes are assessed.

Error Matrix Tool to Overview the Validity of Evidence on Radix Sophorae flavescentis for Chronic Hepatitis B.

Objectives: To introduce a conceptualized visual error matrix tool to overview the validity of evidence by taking Radix Sophorae flavescentis for chronic hepatitis B as an example and to propose recommendations for improving clinical trial design and evidence quality. Methods: The randomized clinical trials and reviews were collected during the conduct of a Cochrane systematic review. The authors used a visual error matrix tool to overview the evidence validity by looking at systematic, random, and design error risks. Systematic errors were measured by the type of evidence. Random errors were expressed by the standard error (SE). Design errors were assessed on the priority of outcome measures and the adequacy of nine design components. Three-dimensional error matrix on benefits and harms were then constructed. Results: The authors included 6 meta-analyses and 28 randomized clinical trials. In terms of systematic errors, all reviews were at critically low quality, and all included randomized trials were assessed at high risk of bias. On this systematic error level, they found that there was substantial risk of random errors regarding all-cause mortality (SE 0.36), moderate risk regarding serious adverse events (SE 0.22), substantial risk regarding nonserious adverse events (SE 0.35), and small to moderate risk regarding surrogate outcomes such as detectable hepatitis B e-antigen (HBeAg) and detectable hepatitis B virus (HBV)-DNA (SE 0.16 and 0.21). No study reported results on quality of life, hepatitis B-related mortality, and morbidity. The design error risks were mainly misuse of outcomes (14/34), inadequate selection of participants (5/34), inadequate description of intervention (11/34) and control (9/34), single-center setting (33/34), and unclear study objective regarding superiority, equivalence, or noninferiority. Conclusion: The current evidence on Radix S. flavescentis for chronic hepatitis B showed high risks of systematic errors, moderate or high risks of random errors, and high risks of design errors. These findings suggest that more randomized trials at minimum risks of all three errors are needed to assess the benefits and harms of Radix S. flavescentis for chronic hepatitis B. The visual error matrix tool provides an overview of the reliability of evidence and may assist in design and conduct of future randomized trials.

Therapy of Dredging the Bowels Enhanced the Neuroprotective Effect of Nourishing Kidney Herbs on Hippocampal Cholinergic System in Alzheimer's Disease Model Rat Induced by Aß 1-42.

BACKGROUND: Therapy of nourishing kidney has been used for treating memory deficits of Alzheimer's disease (AD) for thousands of years based on traditional Chinese medicine. However, we found the therapy of dredging the bowels could alleviate both memory deficits and mental symptoms of AD in clinic. OBJECTIVE: To determine whether the therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs for treating AD rats, and to explore the underlying mechanism of the combination of nourishing kidney and dredging the bowels (NKDB) herbs. METHODS: 60 rats were randomly divided into sham-operated group (SOG), model group (MG), nourishing kidney group (NKG), dredging the bowels group (DBG), nourishing kidney and dredging the bowels group (NKDBG), and donepezil hydrochloride group (DHG). The model establishment was performed by injecting Aß 1-42 into the hippocampal CA1 region. Animals received aqueous solution of Chinese herbal medicine or western medicine while SOG received only distilled water. Ability of learning and memory were assessed by Morris water maze. Acetylcholinesterase(AChE) and choline acetyltransferase (ChAT) activity and positive cells in the hippocampus were detected by the biochemical and immunofluorescent assay. RESULTS: All rats were in the same baseline. While after model establishment, ability of learning and memory of MG, NKG, DBG, NKDBG, and DHG were significantly impaired compared with SOG. Whereas after treatment, ability of learning and memory of NKG, DBG, NKDBG, and DHG were significantly improved compared with MG. Additionally, AChE activity of NKG, DBG, and NKDBG was significantly decreased, meanwhile ChAT activity showed an increased tendency. The number of AChE-positive cells and ChAT-positive cells of both NKDBG and DHG were significantly decreased and increased respectively, superior to those when compared with NKG and DBG. What's more, there was no significant difference between NKDBG and DHG. CONCLUSION: Therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs by reversing morphological damage of hippocampal cholinergic system. Furthermore, treatment with NKDB herbs could be effectively against AD, providing a practical therapeutic strategy in clinic.