The Measures for the Administration of Healthcare Organizations Conducting Investigator-Initiated Trials stipulates that conducting interventional research and observational research that accept additional examinations， tests， diagnostics， and other measures beyond the needs of routine diagnosis and treatment or disease prevention and control， which may pose risks exceeding the minimal risk， must undergo both scientific and ethical reviews. Currently， these two reviews tend to be poorly interfaced and inefficient. This paper analyzed the connections and differences between scientific review and ethical review of investigator-initiated trials （IITs）. It also elaborated the existing issues in the process of interfacing scientific review and ethical review from five aspects， encompassing an immature management system， insufficient awareness of scientific review， failure to understand the different purposes of duplicative review on certain contents， unclear review criteria， and limited professional knowledge and a lack of communication among committee members. Recommendations were proposed from eight dimensions， namely， improving the management system and regulatory measures， coordinating the review time， unifying the document submission checklist， establishing an information system for clinical research management， enhancing training for investigators， providing cross-disciplinary training for committee members， improving the communication mechanisms， and jointly developing the review elements for scientific issues. The aim was to facilitate the efficient interface between scientific review and ethical review for IITs， thereby enhancing the quality and efficiency of IIT management.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use （ICH） issued the ICH E6（R3）： Guideline for Good Clinical Practice on January 14， 2025， which will enhance the speed and quality of global clinical trials， including those in China. As the ethical， scientific and quality standards for global drug clinical trials， the highlights of the revision in the ICH E6 （R3） include encouraging innovation to improve efficiency and quality， motivating research participants to participate in the design and implementation of clinical trials throughout the process， emphasizing quality originating from design and based on the quality management of risks， as well as underlining proportionality and standalone chapter to data governance. ICH E6 （R3） adopts an appendix and appendix structure， enabling future revisions to be more convenient and efficient. ICH E6 （R3） restructures the principles section， adding two new principles and reducing the total from 13 to 11， while incorporating extensive explanatory notes. Major revisions also encompass multiple aspects， including regular review by ethics committees to ensure the safety， rights and interests， and well-being of research participants； diversification of informed consent methods， refinement of its processes， and clarification of detailed rules for minors’ consent； qualifications， authorization， and oversight of investigators and their service providers； risk-proportionate design and implementation by sponsors； joint data governance by investigators and sponsors； and the addition and revision of terms， along with updates to three appendices. The design， implementation， and review of drug clinical trials in China are increasingly aligning with international standards. ICH E6 （R3） will accelerate the revision of China’s Guideline for Good Clinical Practice， promote the speed and quality of drug research and development， and further facilitate the internationalization of China’s new drug research and development.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

The surrogate subjects have been gradually replaced from “legal representatives” to “guardians” in China’s relevant norms regarding the surrogate system of the right to informed consent in clinical research recently. Although this change in the expression of surrogate subjects has not altered its legal essence， it may still lead to ambiguities， confusions and deviations， in the understanding of the surrogate subjects for the right to informed consent. Therefore， this paper summarized its characteristics from three aspects， namely， the changes in relevant norms regarding the surrogate system of the right to informed consent in China’s clinical research， their differences from foreign norms， and their differences from surrogate subjects of the medical right to informed consent. On this basis， the formal identity and substantive emphasis between guardians and legal representatives were compared from a normative perspective. Subsequently， the major reasons for legislators to replace the expression of surrogate subjects were explored from three aspects， including institutional systematization， reinforcement of the best interest principle， and cultural values. Finally， corresponding implementation suggestions were proposed for situations where research participants lack guardians during the exercise of the right to informed consent in clinical research.

The safeguard system for research participants after clinical trial completion in China remains underdeveloped currently， mainly manifested in the lack of follow-up mechanisms， the absence of ethical review， and insufficient supervision by competent authorities， posing potential risks to the long-term welfare and rights and interests of research participants. To practically address this issue， it is necessary to establish a comprehensive and sustainable safeguard framework. It is recommended to clearly define the various welfare and rights and interests of research participants after trial completion， and to establish a scientific compensation mechanism， thereby laying a solid legal foundation for safeguarding work. A comprehensive follow-up system should be developed to provide long-term health monitoring， professional medical consultation， and necessary public education for research participants， with attention to their long-term health risks. It is also vital to strengthen the supervision role of ethical review throughout the entire process and establish a dynamic tracking mechanism for projects to ensure continuity after trial completion. By improving policies， building systems， strengthening oversight， and other aspects， a scientific， standardized， and humanistic clinical trial environment should be developed， ensuring that the rights and interests of every research participant can be fully respected and protected after trial completion.

Access to the clinical application of medical technology is one of the core institutional contents of medical quality management， involving medical quality assurance， the achievement of patient safety goals， and medical service satisfaction. Medical technology is only permitted for clinical use after its safety and effectiveness have been verified through clinical research， as well as evaluated and reviewed by the medical technology clinical application management committee and ethics committee of this medical and health institution. Based on the relevant laws， regulations， and ethical principles， combined with the experience of ethical review in the clinical application of medical technology from some medical and health institutions， a thematic discussion was held to formulate ethical review guidelines for the clinical application of medical technology for references. These guidelines elaborated on the management system for access to the clinical application of medical technology in medical and health institutions， the system of ethics committees and the requirements of review norms， technical plans and their review points， key points for the implementation of informed consent， technical teams and conditions， and other aspects.

Investigator-initiated clinical trials （IIT） are an important part of scientific and technological activities involving human study participants. Among them， high-quality IIT can be used to support the marketing and registration application of drugs， medical devices， and other products when conditions permit. Currently， there is a huge gap between IIT and industry-initiated clinical trials. The use of unlisted products in IIT has problems， such as lack of regulatory support， insufficient research funding support， the need to improve the ability of clinical research management departments， the weakness of professional clinical research teams， and the difficulty of ethics review to match the demands. The challenges could be addressed by improving regulations and conducting pilot trials on a small scale， guaranteeing adequate research funding， strengthening the construction of clinical research management systems， building professional clinical research teams， ensuring the quality of ethical reviews and strict follow-up reviews， shifting from ethical reviews to a system for protecting research participants， and reinforcing training for researchers. Ethics committees should strictly review key points， such as the risk-benefit ratio， informed consent， research funding， compensation for damages， qualifications and equipment of research team members， and management of conflict of interest.

Radiopharmaceuticals play an important role in the diagnosis and treatment of cardiovascular and cerebrovascular diseases， malignant tumors， central nervous system diseases， and other diseases. Under the urgent need for clinical diagnosis and treatment as well as medical development， the clinical research of radiopharmaceuticals has become a hotspot in international research. By analyzing the current situation of clinical research on radiopharmaceuticals in Europe， America， and China， the ethical issues of clinical research on radiopharmaceuticals were elaborated from four aspects， including lack of relevant laws and regulations， a higher risk of radiopharmaceuticals， dilemmas in ethical review， and insufficient radiation protection. Response principles and measures were proposed from four aspects， including improving regulations and policies， enhancing radiological protection for all parties involved in the research， strengthening ethical review， and reinforcing the training of relevant personnel， to enhance the quality and level of clinical research on radiopharmaceuticals.

Objective:To study the characteristics of metabolites in lower resPiratory tract between coal workers' pneumoconiosis patients and dust exposure patients, and compare the differences of metabolites and their main metabolic pathways.Methods:From December 2020 to February 2021, through a prospective cross-sectional study, a total of 26 patients with coal workers' pneumoconiosis (metabolic group of coal workers' pneumoconiosis) were selected from the bronchoalveolar lavage treatment of coal workers' pneumoconiosis and dust exposure in the Respiratory and Critical Care Medicine Department of the 920th Hospital of the Joint Logistics Support Force during the same period. With 19 cases of dust exposure as the control group (dust exposure metabolic group), samples of alveolar lavage fluid were collected from 2 groups. Metabolites of the two groups were quantitatively analyzed by metabonomics technology, and the characteristics of metabolites and their metabolic pathways were compared. The metabolites with potential predictive value were screened by receiver operating characteristic curve (ROC curve) .Results:Through metabolomic analysis of alveolar lavage fluid in the coal workers' pneumoconiosis group and the dust contact group, a total of 28 different metabolites were screened, including trihydroxybutyric acid, alanine, ethanolamine, L-osan, proline (carboxyl), leucine, 2-hydroxyglutaric acid, proline, lactic acid, serine, valine and threonine in the coal workers' pneumoconiosis group. The levels of differential metabolites such as ornithine, isoleucine, threitol, glucose and lysine were higher ( P<0.05). The levels of different metabolites such as sarcoine, pelanoic acid, palmitic acid, heptadecanoic acid, n-butylamine, tetradecanoic acid, isobutylamine, aminoadipic acid, phosphate, uracil and cytosine were higher in the dust exposure group ( P<0.05). Two major metabolic pathways include glycine, serine and threonine metabolism, arginine and proline metabolism, biotin metabolism, and aminoacyl biosynthesis metabolism. Among the 17 metabolites increased in the coal workers' pneumoconiosis group, the AUC of threitol and lactic acid was greater than 0.8, and the specificity and sensitivity of the working characteristic curves of the two metabolites were 80% and 70%, respectively. Conclusion:There were significant differences in the metabolites of lower respiratory tract between patients with coal workers' pneumoconiosis and those exposed to dust, and the differences were related to multiple metabolic pathways. Threitol and lactic acid may have potential predictive value for pneumoconiosis.

Objective:To analyze the Administrative Measures for Investigator- initiated Clinical Research in Medical and Health Institutions and to provide suggestions for its implementation. Methods:By comparing the 2021 trial version with the official version of the Administrative Measures for Investigator- initiated Clinical Research in Medical and Health Institutions issued by the National Health Commission, the State Administration of Traditional Chinese Medicine and the National Administration for Disease Control and Prevention on October 18, 2024, the new, modified and deleted contents of the Administrative Measures for Investigator-initiated Clinical Research in Medical and Health Institutions were sorted out, summarized and interpreted. Measures for the Administration of Investigator- initiated Clinical Research by Medical and Health Institutions. Results:The Administrative Measures for Investigator-initiated Trial in Medical and Health Institutions remains unchanged from its trial version in terms of structure, with 7 chapters and 49 articles, and from 6, 346 words to 6, 520 words. In order to better regulate the rapidly developing investigator-initiated trial in China, and taking into account the current situation of investigator-initiated trial in China, the results of the pilot programme over 3 years and the feedback from the study, the content of the Administrative Measures for Investigator-initiated Trial in Medical and Health Institutions is more in line with the actual situation, and a lot of new details and specific requirements have been added. The main revisions include the joint issue of 3 administrators, which governs medical and health institutions in all aspects; updating the terms and contents with the latest regulations about ethics review; adjusting the scope of scientific review, which is only required for interventional studies; strictly managing observational studies beyond the minimum risk; cancelling the qualifications of medical and health institutions that as sub-centres in multicentre of superscope investigator-initiated trial; emphasizing that medical and health institutions should give the necessary support of manpower and financial resources, encourages the implementation of full life-cycle management of source data in conjunction with actual practice, specifies the adoption of a unified system number to manage matters after the completion of the trail, and emphasizes the declaration of conflict of interest when releasing trail results.Conclusions:In order to effectively implement the Administrative Measures for Investigator-initiated Clinical Research in Medical and Health Institutions shall accelerate the establishment of a clinical research management system, ensure sufficient manpower and financial resources to support clinical research, strengthen the training of Investigator-Initiated Trial management, research, scientific review, ethical review and other personnel, and provide investigators with scientific research outpatient services, implement scientific review based on risk levels, and make it clear that unmarketed products cannot be used in investigator-initiated trials. Refine the qualifications of medical and health institutions participating in off-label investigator-initiated trial.