Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.
Humans ; Medicine, Chinese Traditional ; China ; Reference Standards ; Technology ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM. METHODS: Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM. RESULTS: The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75-0.91) in the training set and 0.79 (0.65-0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74-0.93) and 0.82 (0.66-0.98), respectively. CONCLUSIONS The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
Humans ; Amino Acids ; Cysteine ; Cardiomyopathy, Hypertrophic/diagnosis* ; Biomarkers ; Proline ; Arginine ; Ornithine ; Glycine ; Choline

Human use experience(HUE) is important for the research and development of Chinese medicine. For the sake of more reliable data, the Professional Committee for Clinical Evaluation of Chinese Medicine of Chinese Pharmaceutical Association drafted the Expert Consensus on Human Use Experience Research of Traditional Chinese Medicine. It highlights that the research on HUE should have clear purposes, describe the theoretical basis of traditional Chinese medicine(TCM) for the clinical indications and prescriptions and the clinical value of prescriptions, especially the advantages or characteristics in clinical orientation and target population, evaluate the dosages and number of medicinals of prescriptions, verify the accordance with the preparation process of new Chinese medicine, analyze feasibility of the process for large-scale production and the rationality of the dosage form, and assess the medicinal material resources. Moreover, such research should have reasonable protocol and the collection of clinical data on HUE must comply with medical ethics and avoid conflicts of interest. The collection method should be selected depending on the characteristics of clinical data. Quality control measures should be formulated to ensure the authenticity, accuracy, completeness, reliability, and traceability of clinical data. The definitions on the clinical data should be uniform and clear, and methods should be adopted to avoid bias. The data can be statistically analyzed after the processing. Through the study of HUE, the clinical orientation, target population, commonly used dosage, course of treatment, preliminary efficacy and safety of Chinese medicine prescriptions will be clarified. On this basis, the data on the HUE should be discussed and conclusions will be drawn. Finally, a standardized report will be formed.
Consensus ; Drug Prescriptions ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Reproducibility of Results

This article proposes that the research and development of new Chinese medicines should be based on the clinical values of traditional Chinese medicine(TCM), and expounds the multiple clinical values of new Chinese medicines such as therapeutic effects, adjuvant treatment effects, improvement of disease symptoms, improvement of quality of life, prevention of diseases, etc., so as to broaden the clinical indications of new Chinese medicines. It is pointed out that the clinical value of TCM determines the clinical efficacy evaluation method of new Chinese medicines, so as to construct a clinical evaluation system of new Chinese medicines with the characteristics of TCM. It is proposed that the clinical value of new Chinese medicines should be found under the guidance of TCM theo-ry and clinical practice, and the theoretical innovation of TCM should be emphasized. There is no difference in the clinical value of drugs, and the key is to meet the clinical needs of patients. The research and development of new Chinese medicines ignores the theoretical guidance of Chinese medicine, and relying solely on animal experiment data may lead to failure of clinical trials. Different from the individualized treatment of TCM clinical syndrome differentiation, summarizing the core pathogenesis of TCM is the basis for the development of new Chinese medicines. It is necessary to summarize the pathogenesis of the disease under the guidance of TCM theory and encourage the application of modern medical methods to clarify the diagnosis of the disease. In view of the characteristics of new Chinese medicine research and development, it is proposed that the supporting role of human experience should be emphasized, and the technical points of clinical trials of new syndrome-type Chinese medicines should be explained.The use of objective indicators for syndrome evaluation, the selection of appropriate scales, and the formulation of reasonable treatment courses are advocated. During the research and development of new Chinese medicines, it is not only necessary to pay attention to modern medical safety indicators, but also to observe the evolution of TCM syndromes and specific TCM symptoms.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Quality of Life ; Research ; Syndrome

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.
Biomedical Research ; Clinical Trials as Topic ; Consensus ; Drugs, Chinese Herbal ; Ethical Review ; Humans ; Medicine, Chinese Traditional ; Multicenter Studies as Topic ; Pharmaceutical Preparations

Since "the implementation of good clinical practice"(GCP), especially after 2015, the overall quality of new drug cli-nical trials in China has made significant progress, but compared with developed countries, there are still some obvious quality problems in clinical trials in China. Clinical trials of new drugs of traditional Chinese medicine are an important part of clinical trials of new drugs in China. In addition to some common problems in all clinical trials, there are also some special quality problems. In terms of security data, such as the collection of human safety data is not standardized, the management and judgment of unexpected serious adverse reactions(SUSAR) were not professional and timely, the relationship between adverse events and trial drug was not fully judged by investigator, In terms of effective data, such as primary efficacy outcome of the scale cannot be traced, TCM syndrome data cannot meet the requirements of "source data" in the revised GCP and the quality of traditional Chinese medicine placebo is not high, in terms of overall quality system construction, the sponsors and research institutions have not established a quality assurance system that conforms to the characteristics of new drug research of traditional Chinese medicine, etc. The quality of clinical trials of new drugs of traditional Chinese medicine is based on the current GCP and ICH-GCP in China, we should also consider the characteristics of clinical trials of new traditional Chinese medicine drugs, and formulate targeted quality control measures according to the characteristics of these new drugs of traditional Chinese medicine, to improve the overall quality of clinical trials of new drugs of traditional Chinese medicine in China, which has important strategic significance for promoting the research and development of new drugs of traditional Chinese medicine in China.
China ; Clinical Trials as Topic ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Quality Control

Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Prescriptions ; Reproducibility of Results ; Research

Objective To investigate the effect of microRNA (miR) - 140-3p targeting cell division cycle associated 8(CDCA8) on invasion and metastasis of lung adenocarcinoma cells. Methods The differentially expressed miRNAs were analyzed by GE02R in GEO database. The target genes of miR-140-3p were searched by TargetScan human7. 2 and miRWalk databases. The hub gene was screened by Cytoscape 3. 7. 2 software. GEPIA database was used to query the expression levels of target gene in lung adenocarcinoma tissues and normal lung tissues, the expression levels in different stages of lung adenocarcinoma, and the relationship between the expression levels of target gene and the overall survival rate of lung adenocarcinoma patients. The survival analysis of miR-140-3p in lung adenocarcinoma and the correlation between miR-140-3p and CDCA8 expression levels were searched in starBase database. Real-time PCR was used to detect the expression levels of miR-140-3p in normal lung epithelial cells BEAS-2B and lung adenocarcinoma cells A549, as well as the efficiency of infection. Expression levels of CDCA8 mRNA and protein were detected by Real-time PCR and Western blotting experiments after overexpression of miR-140-3p. Dual-luciferase reporter assay verified whether miR-140- 3p directly binds to CDCA8. Transwell invasion assay detected the effect of overexpression of miR-140-3p and CDCA8 on the invasiveness of lung adenocarcinoma cells. Results Analysis result from GEO and other databases showed that the expression level of miR-140-3p in normal lung tissues was significantly higher than that in lung adenocarcinoma, and its predicted target gene CDCA8 expression level in lung adenocarcinoma was significantly higher than that in normal lung tissues, and CDCA8 was negatively correlated with the expression level of miR-140-3p in lung adenocarcinoma. The experimental result showed that the expression of miR-140-3p in A549 cells was significantly lower than that in BEAS-2B cells (P<0.05). The expression level of miR-140-3p increased significantly after lentiviral infection (P<0.05). CDCA8 mRNA and protein expression levels were significantly down-regulated after overexpression of miR-140-3p (P<0.05). Dual-luciferase reporter assay result showed that miR-140-3p could directly bind to CDCA8 (P<0.05). Compared with the control group, overexpression of miR- 140-3p inhibited the invasion and metastasis of lung adenocarcinoma A549, while CDCA8 reversed the inhibition of miR-140-3p on the invasion and metastasis of lung adenocarcinoma A549 (P<0.05). Conclusion MiR-140-3p targeting CDCA8 inhibits the invasion and metastasis of lung adenocarcinoma cells.