To analyze the registered clinical trial protocols of traditional Chinese medicine(TCM) for the prevention and treatment of coronavirus disease 2019(COVID-19), in order to provide information for improving the quality of research design. The website of the Chinese Clinical Trial Registry(www.chictr.org.cn) and the American Clinical Trial Registry(clinicaltrials.gov) were searched to collect protocols of TCM for COVID-19. Documents were screened following the inclusion criteria, and data were extracted in regard to registration date, study objective, type of design, sponsor, patient, sample size, intervention, and evaluation index. Descriptive analysis was conducted. A total of 49 clinical trial protocols of TCM for COVID-19 were included. Primary sponsors were mainly hospitals or universities in places like Hubei, Beijing, Zhejiang and other regions. The implementation units are mainly in Hubei, Guangdong, Zhejiang, Henan and other regional hospitals. The types of study design were mainly experimental studies(40), including 30 randomized parallel controlled trials, 7 non-randomized controlled trials, 2 single arm trials and 1 consecutively recruited trial; besides, there were also 6 observational studies, 2 health service studies and 1 preventive study. The sample size reached a total of 30 562 cases, with a maximum of 20 000 for a single study and a minimum of 30. The 49 trials subjects included healthy people(3), isolation and observation cases(1), suspected cases(10),confirmed COVID-19 patients(31) and COVID-19 recovery patients(4). Of the 31 trials planned to include confirmed COVID-19 patients, 16 protocols no definite disease classification, 3 with a clear exclusion of severe subjects, 4 with common subjects, 2 with light, common or severe subjects, 1 with light and common subjects, 1 with common or severe subjects, 3 with severe subjects, and 1 with severe or critical subjects. The experimental interventions included Chinese patent medicine(Lianhua Qingwen Capsules/Granules, Huoxiang Zhengqi Dropping Pills/Oral Liquid, Babao Dan, Gubiao Jiedu Ling, Jinhao Jiere Granules, Compound Yu-xingcao Mixture, Jinye Baidu Granules, Shufeng Jiedu Capsuless, Shuanghuanglian Oral Liquid, Tanreqing Injection, Xuebijing Injection, Reduning Injection, Xiyanping Injection), Chinese medicinal decoction and taichi. The primary evaluation outcomes mainly included antipyretic time, clinical symptom relief, novel coronavirus nucleic acid turning to negative, conversion rate of severe cases and chest CT. There was a quick response of clinical research on the prevention and treatment of COVID-19 with TCM, with the current registered protocols covers the whole process of disease prevention, treatment and rehabilitation. However, issues need to be concerned, including unclear definition of patient's condition, unclear research objectives, unclear intervention process and inappropriate outcomes, etc. In addition, researchers should consider the actual difficulties and workload of doctors in epidemic response environment, and make effort to optimize the process and improve the operability of research protocols under the principle of medical ethics.
Betacoronavirus ; COVID-19 ; China ; Clinical Trial Protocols as Topic ; Coronavirus Infections/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral/drug therapy* ; Randomized Controlled Trials as Topic ; Research Design ; SARS-CoV-2 ; COVID-19 Drug Treatment

To investigate the regularity of prescription and clinical syndromes by analyzing the diagnosis and treatment protocols of traditional Chinese medicine(TCM) for coronavirus disease 2019(COVID-19), so as to provide references for syndrome differentiation and relevant researches. The diagnosis and treatment protocols of COVID-19 published by national and regional health authorities were searched, and information was extracted in regard to disease stages, type of syndromes, and prescriptions, etc. Frequency statistics and relative analysis were used to analyze the rule of syndrome differentiation and prescription with TCM, and further discussion on the pathogenesis and progress of the disease. A total of 26 diagnosis and treatment protocols of TCM for COVID-19 were retrieved after screening(including 1 national scheme and 25 regional ones), among which 16 contained aspects of both prevention and treatment, 7 only involved treatment contents and 3 were prevention schemes. The courses of COVID-19 can be divided into early stage, middle stage, severe stage and recovery stage. The pathogeny of COVID-19 in TCM is damp-toxin, with the core pathogenesis of damp-toxin retention in lung and Qi repression. Its pathological features can be summarized as "damp, toxin, obstruction, deficiency". The location of the disease is lung, always involving spleen and stomach, and may further affect heart and kidney in severe cases. The major treatments for each course are Fanghua Shizuo, Xuanfei Touxie(early stage); Qingre Jiedu, Xuanxie Feire(middle stage); Kaibi Gutuo, Huiyang Jiuni(severe stage); Qingjie Yure, Yiqi Yangyin(recovery stage). There were many diagnosis and treatment protocols for COVID-19 have been published, which generally followed the national edition, through with certain personalities in different regional protocols. There were common features with respect to the disease stage, syndrome differentiation, therapeutic principles and methods, as well as prescriptions; the treatment were generally carried out against the core pathogenesis and progress of the disease. Along with the deepening recognition of COVID-19, the diagnosis and treatment protocols are still need further concretization and standardization. We hope researchers and decision-makers can pay more attention to the treatment of Huayu Tongluo in severe and recovery period.
Betacoronavirus ; COVID-19 ; COVID-19 Testing ; Clinical Laboratory Techniques ; Coronavirus Infections/prevention & control* ; Humans ; Medicine, Chinese Traditional ; Pandemics/prevention & control* ; Pneumonia, Viral/prevention & control* ; SARS-CoV-2 ; COVID-19 Drug Treatment

This study aimed to comprehensively analyze and compare the differences of different clinical study types currently published in the safety evaluation of Xuebijing Injection. Six databases, namely the Cochrane Library, PubMed, EMbase, CNKI, VIP and Wanfang database, were electronically retrieved to collect all types of studies on the safety of Xuebijing Injection, including randomized controlled trials, case-controlled studies, cohort studies, systematic reviews, and centralized monitoring studies of clinical safety(hospital), in order to comprehensively and objectively evaluate the safety of Xuebijing Injection, and analyze the differences of different research results. A total of 211 literatures were included, involving a total of 46 384 patients treated with Xuebijing Injection, and 423 adverse reactions(ADRs) occurred. They included 191 randomized controlled trials, 3 cohort studies, 15 systematic reviews, and 2 centralized monitoring studies of clinical safety(hospital), and the incidence of adverse reactions was 2.54%(common), 2.31%(common), 0.95%(occasionally), and 0.50%(occasionally). More than half of the 423 cases of ADRs occurred in skin and adnexal system(151 cases) and gastrointestinal system(65 cases), including such manifestations as rash, skin itching, nausea and vomiting, diarrhea. The degree of ADRs was mild. Randomized controlled trials showed that the incidence of ADR was the highest when Xuebijing Injection was used for malignant tumor and multiple organ failure. And the systematic evaluation showed that the incidence of ADR was the highest when Xuebijing Injection was used for spontaneous peritonitis of liver cirrhosis. In conclusion, different study types could lead to significant differences in the results of drug safety evaluation. Sample size, study type, and quality control are the main factors for biased results. Due to large sample size and high-quality, centralized monitoring studies become the better clinical safety evaluation model of drugs at present, and full life cycle management could more objectively reflect drug safety and guide clinical rational drug use.
Case-Control Studies ; Drug-Related Side Effects and Adverse Reactions/epidemiology* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Injections

To systemically evaluate the efficacy and safety of Maxing Shigan Decoction in the treatment of community acquired pneumonia(CAP) and provide a reference for the treatment of CAP. Databases of CNKI, Wanfang, VIP, SinoMed, EMbase, Cochrane Library, Web of Science and PubMed were searched(from inception to May 30, 2020) to screen the randomized controlled trials(RCTs) of Maxing Shigan Decoction in treating CAP. Two authors independently screened and selected relevant literature and extracted data based on the inclusion and exclusion criteria. Any disagreement or differences was resolved through discussion. The bias risk assessment tool recommended by Cochrane handbook was used to evaluate the quality of the included studies, and RevMan 5.3 software was used for data analysis. Seventeen RCTs were finally included, involving 1 309 patients. Meta-analysis showed that Maxing Shigan Decoction combined with conventional Western medicine treatment could improve clinical efficacy in patients with CAP more effectively as compared with conventional Western medicine treatment alone, mainly in terms of anti-inflammatory effects, a decrease in C-reactive protein(CRP) content(MD=-6.01, 95%CI[-10.95,-1.06], P=0.02)and white blood cell(WBC) count, a decrease in procalcitonin(PCT) level(MD=-0.74, 95%CI[-0.77,-0.71], P<0.000 1), and shortened recovery time of cough and fever. Maxing Shigan Decoction has certain curative effect on CAP, but there are problems in the methodology of included studies. High-quality stu-dies are still needed for further verification.
Community-Acquired Infections/drug therapy* ; Cough ; Drugs, Chinese Herbal ; Humans ; Pneumonia/drug therapy* ; Randomized Controlled Trials as Topic ; Treatment Outcome

To assess the clinical efficacy of Yiqi Huoxue Chinese patent medicine for coronary heart disease with angina pectoris by using network Meta-analysis method. The relative randomized controlled trials( RCTs) of Yiqi Huoxue Chinese patent medicine for coronary heart disease with angina pectoris were retrieved from China National Knowledge Infrastructure( CNKI),Wan Fang,VIP and Chinese Biomedical Literature Database( CBM) in July 2018. Two researchers independently completed the literature screening,data extraction and quality evaluation according to the pre-determined inclusion and exclusion criteria,and the results were cross-checked.The data were analyzed by Win Bugs,and STATA software was used for plotting. Finally,114 RCTs were included,involving 7 Yiqi Huoxue Chinese patent medicines and 11 775 patients. Network Meta-analysis showed that the total effective rate for improvement in AP symptoms had 7 direct comparisons and 21 indirect comparisons,8 of which were statistically significant. The ECG improvement had 7 direct comparisons and 21 indirect comparisons,7 of which were statistically significant. In terms of the total effective rate of improvement in AP symptoms,the order of efficacy was as follows: Shensong Yangxin Capsules > Shexiang Baoxin Pills > Qishen Yiqi Dropping Pills > Tongxinluo Capsules > Wenxin Granules > Qishen Capsules > Naoxintong Capsules. In terms of ECG improvement,the order of efficacy was as follows: Shexiang Baoxin Pills > Tongxinluo Capsules > Naoxintong Capsules > Qishen Yiqi Dropping Pills> Wenxin Granules > Shensong Yangxin Capsules > Qishen Capsules. The results showed that Shensong Yangxin Capsules and Shexiang Baoxin Pills had certain advantages in the treatment of coronary heart disease with angina pectoris. Due to the small sample size,more studies were required to further verify the evidences.
Angina Pectoris ; drug therapy ; China ; Coronary Disease ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Network Meta-Analysis ; Nonprescription Drugs ; Randomized Controlled Trials as Topic

To systematically review the efficacy and safety of Tongmai Yangxin Pills in treatment for angina pectoris of coronary heart disease. CNKI, WanFang, VIP, SinoMed, PubMed, EMbase and the Cochrane Library databases were retrieved online to collect randomized controlled trials(RCTs) of Tongmai Yangxin Pills for angina pectoris of coronary heart disease since the establishment to November 2018. Two investigators screened out literatures independently, extracted data and assessed the risk of bias of included studies. The risk assessment of included references was made according to criteria recommended by Cochrane Handbook 5.3. Meta-analysis was then performed by RevMan 5.3 software. A total of 9 RCTs were included. The results of Meta-analysis showed that compared with the single application of chemotherapy, the combined administration with Tongmai Yangxin Pills and Western medicine could significantly improve the clinical efficacy of angina(RR=1.22, 95%CI[1.13, 1.31]), the improvement rate of electrocardiogram(RR=1.31, 95%CI[1.21, 1.42]), and the clinical efficacy of traditional Chinese medicine(TCM) syndrome(RR=1.17, 95%CI[1.02, 1.35]). Only one study reported adverse events, while 5 studies reported no adverse event. According to current evidences, in the treatment of angina pectoris of coronary heart disease, Tongmai Yangxin Pills has a better clinical efficacy in the treatment of angina pectoris of coronary heart disease in terms of the improvement rate of electrocardiogram and the clinical efficacy of TCM syndrome. Due to the limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions.
Angina Pectoris ; drug therapy ; Coronary Disease ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Electrocardiography ; Humans ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic

To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.
Dementia, Vascular/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Injections ; Medicine ; Salvia miltiorrhiza

To systemically evaluate the efficacy and safety of Gingko Ketone Ester Dropping Pills in treating angina pectoris and co-ronary heart disease. CNKI, Wanfang, SinoMed, PubMed, Cochrane Library and EMbase databases were retrieved on computer, and the randomized clinical trial(RCT) on Gingko Ketone Ester Dropping Pills in treating angina pectoris and coronary heart disease, which were published from the database establishment to December 31, 2019, were comprehensively collected. Literature screening, data extraction and quality evaluation were conducted independently by two researchers according to inclusion and exclusion criteria. Literature methodology quality evaluation was conducted with use of the Cochrane Handbook 5.3.0(bias risk assessment tool). Meta-analysis was performed with RevMan 5.3.0 software. A total of 10 RCTs were included. The results of the Meta-analysis showed that as compared with conventional Western medicine alone, the application of Gingko Ketone Ester Dropping Pills combined with conventional Western medicine treatment further improved the total effective rate and electrocardiogram effect(RR=1.43,95%CI[1.20,1.71],P<0.000 1). There were statistically significant differences in the number of angina attacks, the duration of angina and the amount of nitroglycerin used. In terms of safety indicators, four studies reported adverse reactions in the experimental group, including facial flu-shing, tachycardia, dizziness, dyspnea, nausea and other symptoms. Based on the existing findings, in the treatment of angina pectoris and coronary heart disease, Gingko Ketone Ester Dropping Pills combined with conventional Western medicine can improve the clinical total effective rate, electrocardiogram effect, number of angina attacks, duration of angina and the amount of nitroglycerin used. However, in the included studies, due to some methodological quality problems which would impact the reliability of literature results more high-quality randomized controlled trials are still needed for further verification.
Angina Pectoris/drug therapy* ; Coronary Disease/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Esters ; Ginkgo biloba ; Humans ; Ketones/adverse effects* ; Randomized Controlled Trials as Topic ; Reproducibility of Results

The purpose of this study was to determine the diagnostic accuracy of serum inhibin B (INHB) as a predictor of the retrieval outcome of testicular haploid gametes (spermatids and testicular spermatozoa) in nonobstructive azoospermic men. Serum hormone levels, testicular volume, and histological evaluation were performed in 403 Chinese nonobstructive azoospermic men. Testicular haploid gamete was successfully retrieved in 213 of 403 patients (52.85%). The haploid gamete group always had higher INHB levels than the non-haploid gamete group. According to the receiver operating characteristic (ROC) curve analysis, INHB was a good predictor of testicular haploid gamete retrieval outcome in all patients (sensitivity: 77.93% and specificity: 91.58%) and patients with normal follicle-stimulating hormone (FSH; sensitivity: 88.52% and specificity: 70.83%). The area under the ROC curve (AUC) of INHB was similar to that of FSH in all patients or patients with normal FSH. In patients with elevated FSH, INHB was superior to FSH in predicting the presence of haploid gamete (AUC: 0.73 vs 0.55, P < 0.05), with a sensitivity of 60.00% and a specificity of 80.28%. It concluded that serum INHB as an effective marker for spermatogenesis was a significant predictor of testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men. Especially, INHB is superior to FSH in predicting the presence of haploid gamete in the patients with elevated FSH.
Adult ; Azoospermia/blood* ; Follicle Stimulating Hormone/blood* ; Haploidy ; Humans ; Inhibins/blood* ; Male ; Sensitivity and Specificity ; Sperm Retrieval ; Spermatogenesis/physiology*