Traditional Chinese medicine(TCM) formula granules are highly praised for the advanced, convenient, and modern use of Chinese medicinal materials. The safety of TCM formula granules has long been a concern of regulatory authorities and the medical industry. A multi-center, prospective, open, non-interventional, and centralized monitoring was carried out for the patients treated with TCM formula granules in 252 medical institutions from February 5, 2020 to April 19, 2022. All the case data and the incidence of adverse drug reactions/events were recorded. This study evaluated the safety of TCM formula granules, aiming to provide a reference for the clinically use. A total of 20 547 patients were included in this study. Four adverse events were recorded, including 3 adverse drug reactions with an adverse drug reaction rate of 0.015%, all of which occurred in the digestive system. There was no serious adverse event, and no factors related to adverse drug reactions/events were identified. The incidence of adverse drug reactions/events associated with China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. TCM formula granules was rare, which proved their safety in clinical use. A comprehensive data mining and objective analysis was carried out for the medicines with high frequency in TCM formula granules, the commonly used medicine pairs and combinations, and departmental medication. The drug use characteristics, prescription rules, and departmental use of TCM formula granules were summarized, which can shed light on the prescription compatibility and clinical application.
Humans ; Medicine, Chinese Traditional/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Prospective Studies ; Drug-Related Side Effects and Adverse Reactions/epidemiology* ; China

Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.
Humans ; Medicine, Chinese Traditional ; Oxaliplatin/adverse effects* ; Artificial Intelligence ; Quality of Life ; Drugs, Chinese Herbal/therapeutic use* ; Antineoplastic Agents/adverse effects* ; Cognition

Meta-analysis and integrative bioinformatics were employed to comprehensively study the efficacy, safety, and mechanism of Huangkui Capsules in treating chronic kidney disease(CKD). CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, and Web of Science were searched for randomized controlled trial(RCT) of Huangkui Capsules for CKD from inception to January 3, 2023. The outcome indicators included urine protein, serum creatinine(Scr), and blood urea nitrogen(BUN) levels, and Cochrane Handbook 5.1 and RevMan 5.3 were employed to perform the Meta-analysis of the included RCT. The active ingredients of Huangkui Capsules were retrieved from CNKI, and the targets of CKD from GeneCards, OMIM, and TTD. Cytoscape 3.8.0 was used to build a "component-disease" network and a protein-protein interaction(PPI) network for the screening of core components and targets. Next, a differential analysis of the core targets of Huangkui Capsules for treating CKD was conducted with the clinical samples from GEO to identify the differentially expressed core targets, and correlation analysis and immune cell infiltration analysis were then performed for these targets. A total of 13 RCTs were included for the Meta-analysis, involving 2 372 patients(1 185 in the observation group and 1 187 in the control group). Meta-analysis showed that the Huangkui Capsules group and the losartan potassium group had no significant differences in reducing the urinary protein levels after 12(MD=19.60, 95%CI[-58.66, 97.86], P=0.62) and 24 weeks(MD=-66.00, 95%CI[-264.10, 132.11], P=0.51) of treatment. Huangkui Capsules in combination with conventional treatment was superior to conventional treatment alone(MD=-0.55, 95%CI[-0.86,-0.23], P=0.000 6). Huangkui Capsules combined with conventional treatment was superior to conventional treatment alone in recovering Scr(MD=-9.21, 95%CI[-15.85,-2.58], P=0.006) and BUN(MD=-1.02, 95%CI[-1.83,-0.21], P=0.01). Five patients showed clear adverse reactions, with abdominal or gastrointestinal discomfort. Huangkui Capsules had 43 active ingredients and 393 targets, and the core ingredients were myricetin, quercetin, gossypin, elaidic acid, dihydromyricetin, isochlorogenic acid B, and caffeic acid. CKD and Huangkui Capsules shared 247 common targets, including 25 core targets. The GEO differential analysis predicted 18 differentially expressed core targets, which were mainly positively correlated with immune cell expression and involved in immune inflammation, oxidative stress, pyroptosis, lipid metabolism, sex hormone metabolism, and cell repair. Conclusively, Huangkui Capsules combined with conventional treatment significantly reduced urine protein, Scr, and BUN. Huangkui Capsules alone and losartan potassium had no significant difference in reducing urine protein. This efficacy of Huangkui Capsules may be associated with the multi-component, multi-target, and multi-pathway responses to immune inflammation and oxidative stress. The included RCT had small sample sizes and general quality. More clinical trial protocols with large sample sizes and rigorous design and in line with international norms are needed to improve the evidence quality, and the results of bioinformatics analysis remain to be confirmed by further studies.
Humans ; Losartan ; Renal Insufficiency, Chronic/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Capsules ; Inflammation/drug therapy*

This study reviewed the current status of the use of outcome indicators in randomized controlled trial(RCT) on traditional Chinese medicine(TCM) treatment of microvascular angina(MVA) and analyzed the existing problems and possible solutions, aiming to provide a basis for the design of high-quality RCT and the establishment of core outcome sets for MVA. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries were searched for the RCT on TCM treatment of MVA according to pre-defined criteria. The Cochrane's risk of bias assessment tool was used to evaluate the methodological quality of the included RCT and the use of outcome indicators was summarized. A total of 69 RCTs were included, from which 100 outcome indicators were extracted, with the frequency of 430. The extracted outcome indicators belonged to 8 domains: response rate, symptoms and signs, physical and chemical examinations, TCM efficacy, safety, quality of life, economic evaluation, and long-term prognosis. The indicators of physical and chemical examinations were the most(70 indicators with the frequency of 211), followed by those of response rate(7 indicators with the frequency of 73) and symptoms and signs(7 indicators with the frequency of 54). The outcome indicators with higher frequency were adverse reactions, angina attack frequency, clinical efficacy, endothelin-1, total duration of treadmill exercise, and hypersensitive C-reactive protein. The RCT on TCM treatment of MVA had the following problems: irregular reporting of adverse reactions, diverse indicators with low frequency, lack of attention to the application of endpoint indicators, insufficient use of TCM differentiation and efficacy indicators, non-standard evaluation criteria and failure to reflect the basic characteristics of TCM. A unified MVA syndrome differentiation standard should be established, on the basis of which an MVA treatment efficacy evaluation system and core outcome indicator set that highlights the characteristics of TCM with patient-reported outcomes as the starting point should be established to improve the clinical research and research value.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/adverse effects* ; Microvascular Angina/drug therapy* ; Quality of Life ; Phytotherapy ; Treatment Outcome

This study aims to analyze the outcomes and measurements of randomized controlled trial(RCT) for traditional Chinese medicine(TCM) treatment of endometriosis(EM) and provide a basis for the building of the core outcome set(COS) of EM. The RCT for TCM treatment of EM was retrieved from medical literature databases with the time interval from inception to February 3, 2022. The Cochrane risk of bias assessment tool was employed to evaluate the risk of bias of the included RCT, and descriptive analyses of the extracted information were carried out. A total of 519 RCTs were included, with the sample sizes ranging from 28-582 patients and 239 outcome indicators(8 outcome indicators per RCT on average). According to the functional properties, the reported outcome indicators were classified into 7 indicators: clinical efficacy assessment, indicators of clinical symptoms and signs, TCM symptom efficacy indicators, physical and chemical examinations, quality of life, long-term prognosis, and safety events. All the 519 RCTs had problems, such as the lack of differentiation between primary and secondary outcome indicators(1.73% RCTs reported such differen-tiation), poor quality, confused criteria for composite outcome indicators and arbitrary combination of indicators(45 criteria for the single outcome indicator of efficiency), and messy measurements(as many as 18 measurements for TCM symptom score). In addition, as a chronic disease, EM requires long-term management. The outcome indicators vary for the patients in different disease stages, such as EM pain, EM infertility, and post-operative EM, while the specific outcome indicator sets for different EM populations remain to be developed. In addition, the time point of measurement for EM long-term outcomes remains unclear, and the definition of TCM syndromes lacks standards. The RCT for TCM treatment had a variety of problems, such as the lack of differentiation of outcome indicators, confusion in criteria and measurements, lack of specific outcome indicator sets for different EM populations, and unclear time points for long-term outcomes. Therefore, the studies about COS need to be carried out urgently.
Female ; Humans ; Medicine, Chinese Traditional ; Endometriosis/complications* ; Quality of Life ; Syndrome ; Drugs, Chinese Herbal/adverse effects*

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.
Animals ; Humans ; Medicine, Chinese Traditional/adverse effects* ; Cardiotoxicity ; Induced Pluripotent Stem Cells ; Arrhythmias, Cardiac/chemically induced* ; Myocytes, Cardiac ; Organoids ; Drugs, Chinese Herbal/adverse effects*

This study aims to systematically review the efficacy and safety of different traditional Chinese medicine injections combined with conventional treatment for patients with post-acute myocardial infarction heart failure. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library with the time interval from inception to May 13, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Network Meta-analysis was then performed in RevMan 5.3 and Stata 15.1. A total of 68 RCTs involving 11 traditional Chinese medicine injections and 5 995 patients were included. The results were explained based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of reducing major adverse cardiovascular event(MACE), the therapies followed the trend of Xinmailong Injection+conventional treatment(83.8%) > Yiqi Fumai Injection+conventional treatment(57.1%) > Xuebijing Injection+conventional treatment(56.6%) > Shenmai Injection+conventional treatment(53.1%) > Shenfu Injection+conventional treatment(45.3%) > conventional treatment(4.0%).(2) In terms of increasing left ventricular ejection fraction(LVEF), the therapies followed the trend of Yiqi Fumai Injection+conventional treatment(84.0%) > Shenmai Injection+conventional treatment(69.6%) > Shenfu Injection+conventional treatment(62.7%) > Xinmailong Injection+conventional treatment(61.6%) > Shuxuening Injection+conventional treatment(54.8%) > Shenqi Fuzheng Injection+conventional treatment(46.7%) > Shengmai Injection+conventional treatment(45.9%) > Breviscapine Injection+conventional treatment(39.9%) > Danhong Injection+conventional treatment(38.8%) > Huangqi Injection+conventional treatment(38.7%) > conventional treatment(7.3%).(3) In terms of reducing B-type natriuretic peptide(BNP), the therapies followed the trend of Xinmailong Injection+conventional treatment(98.6%) > Shenmai Injection+conventional treatment(57.7%) > Shenfu Injection+conventional treatment(52.5%) > Shengmai Injection+conventional treatment(30.1%) > conventional treatment(11.0%).(4) In terms of reducing cardiac troponin Ⅰ(cTnⅠ), the therapies followed the trend of Shenmai Injection+conventional treatment(92.3%) > Yiqi Fumai Injection+conventional treatment(61.5%) > Shenfu Injection+conventional treatment(51.2%) > Shengmai Injection+conventional treatment(48.1%) > Xinmailong Injection+conventional treatment(26.6%) > conventional treatment(20.3%).(5) In terms of reducing high-sensitivity C-reactive protein(hs-CRP), the therapies followed the trend of Shenmai Injection+conventional treatment(79.9%) > Xinmailong Injection+conventional treatment(68.1%) > Shenfu Injection+conventional treatment(63.1%) > Xuebijing Injection+conventional treatment(56.7%) > Shengmai Injection+conventional treatment(51.1%) > Shenqi Fuzheng Injection+conventional treatment(42.8%) > Huangqi Injection+conventional treatment(34.7%) > conventional treatment(3.5%).(6) A total of 22 RCTs reported the occurrence of adverse reactions, mainly involving the damage of the circulatory system, digestive system, and coagulation function. The current evidence suggested that Xinmailong Injection+conventional treatment may have the best therapeutic effect in reducing MACE and BNP; Yiqi Fumai Injection+conventional treatment may be the best in increasing LVEF; Shenmai Injection+conventional treatment may be the best in reducing cTnI and hs-CRP. The safety needs further quantitative research and analysis. However, more high-quality RCT is required to validate the above conclusions due to limitations in the quality and quantity of the included studies.
Humans ; Medicine, Chinese Traditional ; Stroke Volume ; Network Meta-Analysis ; C-Reactive Protein ; Ventricular Function, Left ; Drugs, Chinese Herbal/adverse effects* ; Myocardial Infarction/drug therapy* ; Heart Failure/drug therapy*

This study evaluated the clinical effectiveness of Ruyi Zhenbao Pills in the treatment of osteoarthritis, aiming to clarify its clinical advantages and promote rational drug use and related policy transformation. Following the relevant standards in Guidelines for the Comprehensive Evaluation of Drugs in Clinical Practice and Technical Specifications for the Clinical Comprehensive Evaluation of Chinese Patent Medicine, comprehensive research and related data on Ruyi Zhenbao Pills in the treatment of osteoarthritis were collected in the dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and traditional Chinese medicine(TCM) cha-racteristics(referred to as the "6+1" dimensions). Through evidence-based medicine, questionnaire surveys, health technology assessment, pharmacoeconomic evaluation, and other methods, a multi-criteria decision analysis(MCDA) model and CSC v2.0 software were used to comprehensively evaluate the clinical value of Ruyi Zhenbao Pills. Spontaneous reporting system data on adverse reactions and literature data indicate that the adverse reactions of Ruyi Zhenbao Pills are mostly general adverse reactions, with no reports of se-rious adverse reactions. The known risks are small, and its safety is rated as class A. It has been shown to effectively relieve joint pain and restore joint function in the treatment of osteoarthritis. However, more high-quality, large-sample randomized controlled trials are needed to further validate its effectiveness, which is rated as class B. There is evidence supporting its economic viability, and its economic is rated as class B. It demonstrates good clinical innovation, innovative enterprise service system, and industrial innovation, and innovation is rated as class A. Medical professionals and patients have a favorable perception of the suitability of Ruyi Zhenbao Pills, and further improvement can be made in terms of convenience of administration and promotion to facilitate rational drug use by healthcare professionals and patients. Suitability is rated as class B. The drug has a favorable price level, availability, and affordability, and accessibility is rated as class A. Ruyi Zhenbao Pills are a classic Tibetan medicinal prescription with excellent TCM theoretical characteristics. However, further research is needed on its use in human studies. TCM characteristics are rated as class B. Based on the evaluation results of the "6+1" dimensions, the comprehensive clinical evaluation is rated as grade B. Ruyi Zhenbao Pills have good clinical value in the treatment of osteoarthritis, and it is recommended to undergo the necessary procedures for conditional transformation into a policy for the management of essential clinical drugs.
Humans ; Medicine, Chinese Traditional ; Reference Standards ; Nonprescription Drugs ; Drugs, Essential ; Osteoarthritis/drug therapy* ; Drugs, Chinese Herbal/adverse effects*

This study aims to systematically review the efficacy and safety of Shufeng Jiedu Capsules in the treatment of influenza. The randomized controlled trial(RCT) of Shufeng Jiedu Capsules alone or in combination with conventional western medicine for treating influenza were retrieved from PubMed, EMbase, Cochrane Library, Web of Science, SinoMed, CNKI, VIP, Wanfang, and ClinicalTrails.gov. The data analysis was performed in RevMan 5.4.1. The Cochrane risk of bias assessment tool was used to evaluate the quality of the involved RCT, and GRADEpro GDT to assess the quality of the evidence. A total of 11 RCTs involving 1 836 patients were included in this study. Compared with conventional western medicine, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.09, 95%CI[1.03, 1.15], P=0.002), shortened the time to relief of cough, and increased the 3-day sore throat relief rate, whereas there was no significant difference in the time to fever abatement, the time to relief of sore throat, 3-day cough relief rate, or 3-day runny nose relief rate. Subgroup-analysis showed that Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.11, 95%CI[1.08, 1.15], P<0.000 01), shortened the time to relief of cough, and increased the 3-day relief rate of symptoms(cough, sore throat, and runny nose) compared with conventional western medicine alone, while there was no significant difference in the time to fever abatement or the time to relief of sore throat. Shufeng Jiedu Capsules alone could not improve the response rate(RR=0.97, 95%CI[0.93, 1.02], P=0.19). In addition, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine vs conventional western medicine were no significant difference in adverse reactions(RR=0.98, 95%CI[0.57, 1.69], P=0.95). The available evidence suggests that Shufeng Jiedu Capsules is effective and safe in the treatment of influenza, and the combination of Shufeng Jiedu Capsules with conventional western medicine can accelerate the relief of symptoms. However, since the number and quality of the included studies were low, the above findings remained to be further verified by multicenter RCT with large sample sizes.
Humans ; Influenza, Human/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Capsules ; Cough/chemically induced* ; Pharyngitis ; Rhinorrhea ; Multicenter Studies as Topic

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.
Mice ; Animals ; Mice, Obese ; Diet, High-Fat/adverse effects* ; Gastrointestinal Microbiome ; Network Pharmacology ; RNA, Ribosomal, 16S ; Diabetes Mellitus, Type 2/complications* ; Obesity/genetics* ; Body Weight ; Lipids ; Insulin ; Transcription Factors ; Dyslipidemias/genetics* ; Mice, Inbred C57BL ; Drugs, Chinese Herbal