Effectiveness of Zhenqi Buxue Oral Liquid Combined with Progesterone for Treatment of Oligomenorrhea and Hypomenorrhea with Qi-Blood and Kidney (Shen) Essence Deficiency: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency.@*METHODS@#This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded.@*RESULTS@#TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment.@*CONCLUSIONS@#The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.

Network Meta-analysis of Chinese patent medicines in treatment of idiopathic membranous nephropathy / 中国中药杂志

This study aimed to systematically evaluate the efficacy and safety of different Chinese patent medicines in the treatment of idiopathic membranous nephropathy. The relevant randomized controlled trial(RCT) was retrieved from PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP with the time interval from database inception to December 2022. The Cochrane risk of bias assessment tool was employed to evaluate the quality of the included RCT, and Stata 15.0 and GEMTC to perform the Bayesian network Meta-analysis. Finally, 51 RCTs were included, involving 9 Chinese patent medicines and 3 591 patients. The results of network Meta-analysis showed that in terms of the total effective rate and the increase in plasma albumin, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Bailing Capsules + conventional western medicine, and Tripterygium Glycosides Tablets + conventional western medicine. In terms of reducing 24-hour urine total protein, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Shenfukang Capsules +conventional western medicine, and Huangkui Capsules + conventional western medicine. In terms of reducing serum creatinine, the top three interventions were Shenfukang Capsules + conventional western medicine, Bailing Capsules + conventional western medicine, and Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine. In terms of safety, Chinese patent medicines combined with conventional western medicine had fewer adverse reactions than the control group. The results suggest that Chinese patent medicines combined with conventional western medicine can improve the therapeutic effect on idiopathic membranous nephropathy, and differentiated medications can be adopted according to the specific symptoms of patients in clinical treatment. Further validation needs to be carried out in the future with multi-center, large-sample, and high-quality RCT.

Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis / 中国中药杂志

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.

New outlook on safety of traditional Chinese medicine: concept and practice / 中国中药杂志

Profound changes have taken place in human disease spectrum, constitution spectrum, and drug use behavior, and the safety of traditional Chinese medicine(TCM) faces new trends and problems. In particular, serious adverse reactions/events such as liver injury and kidney injury caused by non-toxic TCM have been frequently reported, overturning people's understanding of TCM safety, and even shaking the public's confidence in the development of TCM. In the new era of globalization, correctly understanding the situation and problems of TCM safety and addressing the dilemmas in safety evaluation and risk prevention of TCM are the key missions to be undertaken by TCM practitioners. This paper suggests that the situation and problems of TCM safety should be viewed objectively and dialectically, and the use standard of TCM should be advanced with the times. Furthermore, this paper puts forward the new conception and methodology of TCM safety(including one innovative understanding, two types of evaluation modes, tri-elements injury hypothesis; four-quadrant risk decision processes, and five-grade safety evidence body) for the first time, hoping to provide new theories, new strategies, new methods and successful examples for solving the safety problems of TCM.

Expert consensus for Jingtong Granules in treatment of cervical radiculopathy in clinical application / 中国中药杂志

With the effects of activating blood and resolving stasis, and moving Qi to relieve pain, Jingtong Granules is widely used in the treatment of cervical radiculopathy in China. Long-term clinical application and related evidence have shown that the prescription has ideal effect in alleviating the pain in neck, shoulder, and upper limbs, stiffness or scurrying numbness, and scurrying pain caused by this disease. However, there is a lack of consensus on the clinical application of Jingtong Granules. Therefore, clinical first-line experts and methodology experts from all over the country were invited to compile this expert consensus. This expert consensus is expected to guide clinicians to use Jingtong Granules in a standardized and reasonable way, improve clinical efficacy, reduce medication risks, and benefit patients. First, according to the clinical experience of experts and the standard development procedures, the indications, syndrome characteristics, clinical advantages, and possible adverse reactions of Jingtong Granules were summarized. Then, through face-to-face interview of clinical doctors in traditional Chinese medicine and western medicine and survey of the clinical application, the clinical problems were summed up, and the consensus was reached with the nominal group method to form the final clinical problems. Third, evidence retrieval was carried out for the clinical problems, and relevant evidence was evaluated. The GRADE system was employed to rate the quality of evidence. Fourth, 5 recommendation items and 3 consensuses items were summarized with the nominal group method. Opinions and peer reviews on the consensus content were solicited through expert meetings and letter reviews. The final consensus includes the summary of evidence on the clinical indications, effectiveness, and safety of Jingtong Granules, which can serve as a reference for clinicians in hospitals and primary health institutions.

Systematic review and Meta-analysis of efficacy and safety of Shufeng Jiedu Capsules in treatment of influenza / 中国中药杂志

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.

Clinical comprehensive evaluation of Ruyi Zhenbao Pills in treatment of osteoarthritis / 中国中药杂志

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.

Network Meta-analysis of efficacy and safety of different traditional Chinese medicine injections in treating post-acute myocardial infarction heart failure / 中国中药杂志

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.

hiPSCs and organoids: prediction of arrhythmogenic risks for optimized traditional Chinese medicine / 中国中药杂志

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.

Outcomes and measurements of randomized controlled trial for traditional Chinese medicine in treatment of endometriosis / 中国中药杂志

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.

Outcome indicators in clinical trials on traditional Chinese medicine treatment of microvascular angina / 中国中药杂志

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.

Efficacy, safety, and mechanism of Huangkui Capsules in treating chronic kidney disease: Meta-analysis and integrative bioinformatics / 中国中药杂志

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.

Clinical centralized safety monitoring and evaluation of traditional Chinese medicine formula granules / 中国中药杂志

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.

Meta-analysis and GRADE evaluation of Guanxinning Tablets in treatment of angina pectoris of coronary heart disease / 中国中药杂志

This study aims to evaluate the efficacy and safety of Guanxinning Tablets+conventional western medicine in the treatment of angina pectoris of coronary heart disease, and provide evidence-based references for clinical medication. Retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, randomized controlled trial(RCT) about Guanxinning Tablets for the treatment of angina pectoris of coronary heart disease from the inception to April 2022 were collected. After literature screening and data extraction, the bias risk assessment tool recommended by the Cochrane evaluation manual handbook 5.1.0 was used to evaluate the quality of the included literature, and RevMan 5.3 and Stata 14.0 were used for Meta-analysis. Eighteen RCTs were finally included, involving 2 281 patients. Meta-analysis showed that, compared with conventional western medicine treatment alone, Guanxinning Tablets+conventional western medicine significantly improved angina pectoris efficacy(RR=1.33, 95%CI[1.13, 1.57], P=0.000 8), electrocardiogram efficacy(RR=1.32, 95%CI[1.02, 1.71], P=0.03), and exercise duration(MD=59.53, 95%CI[39.16, 79.90], P<0.000 01) and reduced the incidence of cardiovascular events(MACE)(RR=0.43, 95%CI[0.30, 0.61], P<0.000 01), high sensitivity C-reactive protein(hs-CRP)(MD=-2.75, 95%CI[-3.71,-1.79], P<0.000 01), and endothelin-1(ET-1) levels(MD=-9.34, 95%CI[-11.36,-7.32], P<0.000 01). There was no statistically significant difference in the incidence of adverse reactions between two groups(RR=0.91, 95%CI[0.68, 1.22], P=0.52). Subgroup analysis showed that Guanxinning Tablets may have better short-term efficacy(less than 6 months) in the treatment of heart-blood stasis syndrome. GRADE grading showed that angina pectoris efficacy, electrocardiogram efficacy, MACE, and ET-1 were in the medium grade, hs-CRP and adverse reactions were in the low grade, and exercise duration was in the extremely low grade. In conclusion, the efficacy of Guanxinning Tablets+conventional western medicine is better than conventional western medicine treatment alone, with good safety. Therefore, it is recommended for the short-term treatment of patients with heart-blood stasis syndrome. However, the evidence quality of some results is low, and more rigo-rous RCT is still needed to enhance the reliability of evidence.

Efficacy and Safety of Lianhua Qingwen for Patients with COVID-19: A Systematic Review and Meta-Analysis / 中国结合医学杂志

BACKGROUND@#Corona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19.@*OBJECTIVE@#To evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis.@*METHODS@#A comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group.@*RESULTS@#Nine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05).@*CONCLUSIONS@#LHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).

Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis / 中国结合医学杂志

OBJECTIVE@#To screen the active components from Fuzheng Huayu Recipe (FZHY) and redesign a new recipe composed of the active components, and validate the effect of active components formulation from FZHY against liver fibrosis.@*METHODS@#Thirty-two components from FZHY were evaluated for their activities against liver fibrosis respectively, with 6 kinds of cell models in vitro, including oxidative stressed hepatocyte in L-02, hypoxia injured/proliferative hepatic sinusoidal endothelial cells in SK-HEP-1 and human hepatic sinusoidal endothelial cells (HHSEC), and activated hepatic stellate cell in LX-2. The comprehensive activity of each component against liver fibrosis was scored according to the role of original herbs in FZHY and cell functions in fibrogenesis. Totally 7 active components were selected and combined with equal proportion to form a novel active components formulation (ACF). The efficacy of ACF on liver fibrosis were evaluated on activation of LX-2 and proliferation of HHSEC in vitro and in liver fibrosis model mice induced by dimethylnitrosamine (DMN). Totally 72 mice were divided into 6 groups using a random number table, including normal, high-dose ACF control (20 µ mol/L × 7 components/kg body weight), model, low-, medium-, high-dose ACF groups (5, 10, 20 µ mol/L × 7 components/kg body weight, respectively). Hematoxylin eosin and Sirius red stainings were used to observe inflammation and fibrosis change of liver tissue; scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to observe the effect of ACF on ultrastructure of hepatic sinusoids.@*RESULTS@#Fifteen components from FZHY showed higher scores for their activity on against liver fibrosis. Among them, 7 components including tanshinone II A, salvianolic acid B, cordycepin, amygdalin, quercetin, protopanaxatriol, and schizandrin B were recombined with equal proportions to form ACF. ACF at 1,2, 4 µ mol/L showed strong inhibitory effects on activation of LX-2 and proliferation of HHSEC in vitro (all P<0.01). Compared with the model group, ACF attenuated liver collagen deposition, improved sinusoidal capillarization in a dose-dependent manner (all P<0.05).@*CONCLUSION@#ACF exerts a satisfactory effect against experimental liver fibrosis and attenuates sinusoidal capillarization, which warrant a further research and development for herbal components formulation on liver fibrosis.

Network Meta-analysis of efficacy and safety of oral Chinese patent medicines combined with conventional western medicine in treatment of hypertension / 中国中药杂志

This study aims to systematically evaluate the effect of oral Chinese patent medicines on hypertension with network Meta-analysis. Randomized controlled trials on the treatment of hypertension with oral Chinese patent medicine combined with conventional western medicine were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library(from establishment of the database to August 2021). Two researchers independently screened the articles, extracted the data, and evaluated article quality. Then R 4.1.0 was employed for data analysis. Finally, 195 eligible articles were screened out, involving 22 546 patients and 18 oral Chinese patent medicines. The results of the network Meta-analysis are as follows. In terms of reducing systolic blood pressure(SBP) and diastolic blood pressure(DBP), Xuesaitong, Qiangli Dingxuan Tablets, Songling Xuemaikang Capsules combined with conventional western medicine are superior. In improving blood lipids, the overall effects of Xinmaitong Capsules, Compound Xueshuantong Capsules, Ginkgo Folium preparations, Yindan Xinnaotong Soft Capsules, and Naoxintong Capsules combined with conventional western medicine are outstanding. In terms of regulating endothelial function, Yindan Xinnaotong Soft Capsules, Xinmaitong Capsules, Zhenju Jiangya Tablets, Compound Danshen Dripping Pills, Xuesaitong with conventional western medicine have certain advantages. As for the safety, the incidence of adverse reactions of conventional western medicine combined with oral Chinese patent medicines is lower than that of conventional western medicine alone. In summary, compared with conventional western medicine alone, the 18 oral Chinese patent medicines combined with conventional western medicine in the treatment of hypertension show advantages in improving blood pressure, blood lipids, and endothelial function. Among them, Xuesaitong, Qiangli Dingxuan Tablets, and Songling Xuemaikang Capsules may be the best oral Chinese patent medicines for lowering blood pressure. The conclusion needs to be further verified by more high-quality studies.

Network Meta-analysis of efficacy and safety of Chinese patent medicines in treatment of ankylosing spondylitis / 中国中药杂志

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of ankylosing spondylitis(AS) by frequency network Meta-analysis. Randomized controlled trials(RCTs)of Chinese patent medicines for AS were retrieved from CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library databases from the time of database establishment to January 2021. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 12 kinds of Chinese patent medicines in 55 RCTs were included. According to Meta-analysis, in term of the effectiveness, the top three optimal medication regimens were Biqi Capsules, Yishen Juanbi Pills and Yaobitong Capsules combined with western medicine. The top three interventions to reduce the erythrocyte sedimentation rate(ESR)were Yishen Juanbi Pills, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. The top three interventions to reduce the C-reactive protein(CRP)were Biqi Capsules, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. In terms of the safety, top three optimal medication regimens were Total Glucosides of Paeony Capsules, Yishen Juanbi Pills, and Wangbi Tablets combined with western medicine. This network Meta-analysis suggests that Chinese patent medicines combined with conventional western medicine can effectively improve the joint pain symptoms of AS patients and reduce the acute inflammatory indicators, with high safety. However, the literature included in this study is generally of low methodological quality, and the conclusion needs to be verified by high-quality research.

Clinical comprehensive evaluation of Guanxin Shutong Capsules in treatment of coronary heart disease angina pectoris with heart blood stasis syndrome / 中国中药杂志

This study aims to comprehensively summarize articles on the treatment of coronary heart disease angina pectoris with heart blood stasis syndrome(CHD-AP-HBSS) by Guanxin Shutong Capsules(GSC), and comprehensively evaluate the evidence and value of the formula in "6+1" dimensions based on multi-criteria decision analysis(MCDA) model and Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021) with quantitative and qualitative methods, which is expected to highlight the clinical characteristics and advantages of the prescription and serve as a reference for medical and health departments. The dimensions are grade A, B, C, or D. In terms of safety, according to the reports from the spontaneous reporting system of National Center for ADR Monitoring, and literature analysis, GSC mainly results in the adverse reactions of mild or moderate nausea, diarrhea, rash, palpitation, and headache, with favorable prognosis in patients. Nevertheless, severe adverse reactions have been reported after marketing. Thus, additional evidence for its safety should be accumulated, and the current safety is grade B. Meta-analysis proves that GSC in combination with conventional treatment is superior to conventional treatment alone in alleviating AP and symptoms indicated by electrocardiogram(ECG). Therefore, the effectiveness of the medicine is grade A. As for the pharmacoeconomic value, based on the assumption that the per capita disposable income in 2020 is the willingness-to-pay threshold, it is more economical for CHD-AP patients to use GSC combined with conventional treatment than conventional treatment alone. However, as the currently available clinical parameters fail to support the difference in indirect cost between the two groups, the accuracy in the cost of intervention plan needs to be further improved. Therefore, the economy of the prescription is grade B. GSC has been awarded 13 national invention patents and 1 utility model patent, and won a lot of national and provincial patent awards, marking the enterprise service awareness and innovativeness. As a result, it is grade A in aspect of innovation. A questionnaire on the suitability of GSC suggests that publicity and promotion influence patients' choice and thus additional efforts should be made in this aspect. The suitability of this formula is grade B. Both rural and urban residents can afford the medicine for the whole course and the price is close to that of similar Chinese patent medicines. In addition, it is accessible regardless of season and place, so accessibility is grade A. As a Mongolian empirical formula destined to treat heart stabbing pain, it has the effects of activating blood and resolving stasis, dredging channels and activating collaterals, and moving Qi to relieve pain, and boasts the empirical evidence of more than 2 000 human cases. With prominent characteristics of traditional Chinese medicine, it is grade B. Based on the MCDA model and CSC v2.0, GSC is comprehensively class A in the treatment of CHD-AP-HBSS. The result can serve as a reference for basic clinical medication management.

Interpretation of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions / 中国中药杂志

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.