Application of real world study and human use experience in research and development of new traditional Chinese medicine drugs / 中国中药杂志

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.

Application of add-on-design in post-marketing evaluation of traditional Chinese medicine / 中国中药杂志

Post-marketing evaluation of traditional Chinese medicine(TCM) is an important research stage in the life cycle of a drug, and the add-on-design is a common method for its post-marketing evaluation. This article introduces the basic concept of add-on-design, and points out that it is suitable for use based on the principles of medical ethics when the standard treatment should not be interrupted. The post-marketing evaluation of TCM should be carried out based on human experience and in compliance with regulations and ethics. The clinical values of TCM, such as the therapeutic effect for disease, improvement of disease symptoms, improvement in quality of life, as well as the synergism and toxicity attenuation of combined use of TCM and chemical drugs, should be fully reflected through the clinical trials designed with add-on-design. The key points of add-on-design are accurate clinical positioning, scientific estimation of sample size, and rigorous standard treatment. Standard treatment should be a recognized one, consistent and stable; appropriate and recognized efficacy indicators and targeted safety indicators should be selected; the design and operation of clinical research scheme should meet the requirements of randomization and blind method, with special emphasis on the production of qualified placebo. The add-on-design has the advantages that the rights and interests of the subjects are adequately protected. Besides, the research conclusions are easily put into clinical application. But there are also many difficulties, such as the influence of confounding bias, the "ceiling" effect of clinical efficacy, and the difficulty of interpretation of adverse events. Therefore, a rigorous research quality assu-rance system should be established, and the quality control of evaluation consistency of researchers should be emphasized to ensure strict quality control in the research process.

Development of clinical trial of new drugs of traditional Chinese medicines / 中国中药杂志

The relevant laws and regulations of drug clinical trials were introduced in this paper. It is pointed out that with drug re-gulatory laws and technological advances, clinical trials have become an important link in the development of new drugs of traditional Chinese medicines(TCM). Clinical trials of new drugs of TCM must comply with the requirement of "Good Clinical Practice for Trial on Medicinal Products". In view of the particularities of clinical trials of new drugs of TCM, China has established an ethical review system for clinical research in TCM and carried out ethical review and certification of TCM research. In order to guide the development of clinical trials of new drugs of TCM, relevant departments have promulgated a series of guidelines for clinical trials of it, and established a new review system and technical requirements for clinical trials. Since 1983, the "national clinical pharmacology base" has been established. At present, there are 96 drug clinical trial institutions and 32 phase I clinical research wards in TCM hospitals, which can meet the development of clinical trials of new drugs of TCM. In the long-term practice, the technical team has continued to grow and develop, the research experience and technical strength have been significantly improved, and a large number of experts have become the backbone of clinical research in Chinese medicine. It is pointed out that we should attach importance to risk and benefit assessment, human experience, select scientific, objective and appropriate effectiveness indexes, evaluate the efficacy of TCM syndromes, and encourage the use of electronic methods in clinical research of new drugs of TCM. Based on the analysis of clinical trials of TCM in recent five years, it is pointed out that the active degree of clinical trials of new drugs of TCM is not high, the innovation ability of it is insufficient and the ability and enthusiasm of all aspects need to be improved. It is of great significance to carry out clinical trials of new traditional Chinese medicines to upgrade the TCM industry and produce high-level evidence-based medicine evidences. The high quality development of TCM can be promoted by strengthening clinical trials of new drugs of TCM.

Theoretical thinking on guiding research and development of new drugs of traditional Chinese medicine / 中国中药杂志

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.

Data collection, quality and evidence formation for human use experience of traditional Chinese medicine / 中国中药杂志

Collecting and summarizing human use experience(HUE) data, forming high-quality data and evidences that can be used for evaluation are the key links of HUE research on traditional Chinese medicine(TCM). The collection, collation and summary of human experience data were discussed in this paper. It is pointed out that the collection of HUE should be focus on the source of prescription of new traditional Chinese medicines, and be summarized based on dialectical thinking, experience in medication, characte-ristics of prescription and clinical application. The collected contents include prescription, process, clinical location and applicable population, efficacy data and safety data, etc. The methods include interview, clinical data summary and data mining. When the data formed based on HUE information is used as drug registration information, it is necessary to ensure that the data source is legal and compliant, and the ownership of intellectual property is clear.Data sources should meet the requirements of medical ethics. To avoid conflict of interest, data analysis should be conducted by an independent third party. It is necessary to develop the quality control measures of HUE data to ensure the data traceability, integrity, consistency and accuracy, and avoid data bias.The data of HUE should include the key data such as accurate clinical location and applicable population, recognized clinical efficacy and safety.After the formation of HUE, the statistical analysis plan of empirical data of human use should be formulated. Through strict data processing, statistical analysis and clinical interpretation, HUE can be produced for evaluation.

Research Progress of C-Myc in Chronic Myelogenous Leukemia --Review / 中国实验血液学杂志

As a potential target for cancer treatment, the C-Myc high expresses abnormally in a variety of solid tumors and hematological malignancies in humans. In hematologic malignancies, the increasing expression of C-Myc is associated with poor prognosis of patients diffuse large B-cell lymphoma. However, some studies have shown that high expression of C-Myc might be one of the mechanisms of disease progression and abrupt change, therefore, it can promote the transformation of chronic myeloid leukemia. Besides, the high expression of C-Myc may lead to the decrease of the sensitivity of chronic myelogenous leukemia cells to imatinib. Therefore, C-Myc has been concerned in the study of imatinib drug resistance. This review will focuses on the latest research progress on the mechanism of C-Myc in chronic myeloid leukemia in recent years.

Effects of Ubiquitination on the Expression of BCL6 Protein，Cell Proliferation and Apoptosis in K562/G01 Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the the effects of ubiquitin-proteasome system (UPS) on BCL6 protein level，proliferation and apoptosis of cell imatinib（IM）-resistant K562/G01 cells.@*METHODS@#Western blot was used to detect the expression of BCL6 in K562/G01 cells before and after treatment with protease inhibitor MG-132.The RT-PCR and Western blot respectively were used to detect the mRNA and protein expression levels of BCL6 and USP2 in K562/G01 cells treated with or without ML364 (a ubiquitin-specific protease USP2 inhibitor). The effects of IM alone or in combination with ML364 on proliferation and apoptosis of K562/G01 were analysed by CCK-8 method and flow cytometry.@*RESULTS@#After treatment with protease inhibitor MG132, the BCL6 protein level of K562/G01 significantly increased (P<0.05). The mRNA and protein expression level of ubiquitin-specific protease USP2 in K562/G01 cell line was higher than that in K562 cell line (P<0.05). After treatment of K562/G01 with USP2 protease inhibitor ML364, the expression levels of USP2 and BCL6 proteins were down-regulated simultaneously (P<0.05) . After combination of ML364 and IM, both the proliferation inhibitory rate and the apoptosis rate of K562/G01 cells significantly increased(P<0.05).@*CONCLUSION@#ML364 decreases the BCL6 protein stability in K562/G01 by inhibiting the USP2-mediated deubiquitination, and down-regulate the BCL6 protein experssion, thereby increases the sensitivity of drug-resistant cells to IM.