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.

By reviewing relevant literature and policies on ethical review of clinical application of medical technologies,this study summarizes the necessity,difficulties,and countermeasures for ethical follow-up review,aiming to provide references for its implementation.The challenges in ethical follow-up review include:lack of top-level design at the national level;absence of standardized responsibility entities,requirements,and criteria for follow-up review;overemphasis on interim inspections while neglecting follow-up review,leading to incomplete ethical oversight;insufficient communication and coordination between relevant administrative departments and ethics committees;and weak awareness,low prioritization,and poor compliance among technology leaders regarding follow-up review.Due to the current fragility of ethical follow-up review in clinical application of medical tech-nologies,ethics committees fail to fully fulfill their patient protection responsibilities.To strengthen follow-up review,the follow-ing strategies are proposed:national-level improvement of regulatory frameworks;enhanced interdepartmental coordination within healthcare institutions to establish collaborative supervision mechanisms;intensified training for ethics committee members to im-prove review capabilities;and proactive transformation of ethics committees from passive to active follow-up review.

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 implement the new requirements of the scientific review of investigator-initiated trail in Admin-istrative Measures for Investigator-initiated Trial in Medical and Health Institutions,and to consider its implementation measures.Methods This paper summarized the current status of scientific review of investigator-initiated trial in China,analyzed the new requirements of scientific review in Administrative Measures for Investigator-initiated Trial in Medical and Health Institutions,and put forward suggestions for standardizing and efficiently implementing scientific review.Results The analysis found that the sci-entific review of investigator-initiated trial in China has the following status:most provinces and cities are still in the stage of ex-ploring and implementing scientific review,there is no scientific review system,rules and procedures at the national level,the scientific review system,rules and procedures of the provinces and cities that have been tried out still need to be improved,most medical and health institutions and their superior regulatory agencies are still in the initial stage of review and supervision,and the scientific review awareness of investigators and their corresponding education and training are lacking.Administrative Meas-ures for Investigator-initiated Trial in Medical and Health Institutions put forward new requirements for scientific review,including medical and health institutions should formulate scientific review systems,rules and procedures to implement scientific review,and only need to carry out scientific review for observational research and interventional research that exceed the minimum risk,and need to strengthen the follow-up management of scientific review.Conclusion In order to standardize and efficiently imple-ment scientific review,the recommended measures include designation of the organization and the management department respon-sible for scientific review by medical and health institutions,the provision of human,financial and material support by medical and health institutions,the formulation of scientific review work systems and standard operating procedures that comply with laws and regulations and can be effectively operated,the implementation of scientific review according to the risk level,the close link-age of scientific review with project application and ethics review to reduce the burden on investigators,and the procedures and research methodology of scientific review for medical and health institutions to be trained in a dragnet manner,counseling services are provided to investigators when necessary.

Decentralized clinical trials(DCT)must adhere to the core concept of"patient-centered".DCT has many advantages,such as faster recruitment of diverse study participants,lower participation costs,increased compliance,friendliness to study participants,electronic informed consent,expedited investigational medical product delivery,and convenient data collec-tion.DCT in China faces new requirements for both clinical trial institutions and medical services,inadequate support for infor-mation systems,compliance with electronic informed consent,higher requirements for data security and personal information pro-tection,and the need for multiple training,and other challenges.To accelerate the implementation of DCT in China,the author believes that the following measures can be taken,such as strengthening the construction of information infrastructure to facilitate the participation of grassroots medical institutions and data collection of study participants;establishing communication channels and strengthening training;carefully designing the protocol,establishing standard operating procedures for clinical trials,and strengthening ethical review;conducting remote safety monitoring and reporting safety information;clarifying the data reporting procedure and obtaining high-quality trial data through data collection and management.

By reviewing relevant literature and policies on ethical review of clinical application of medical technologies,this study summarizes the necessity,difficulties,and countermeasures for ethical follow-up review,aiming to provide references for its implementation.The challenges in ethical follow-up review include:lack of top-level design at the national level;absence of standardized responsibility entities,requirements,and criteria for follow-up review;overemphasis on interim inspections while neglecting follow-up review,leading to incomplete ethical oversight;insufficient communication and coordination between relevant administrative departments and ethics committees;and weak awareness,low prioritization,and poor compliance among technology leaders regarding follow-up review.Due to the current fragility of ethical follow-up review in clinical application of medical tech-nologies,ethics committees fail to fully fulfill their patient protection responsibilities.To strengthen follow-up review,the follow-ing strategies are proposed:national-level improvement of regulatory frameworks;enhanced interdepartmental coordination within healthcare institutions to establish collaborative supervision mechanisms;intensified training for ethics committee members to im-prove review capabilities;and proactive transformation of ethics committees from passive to active follow-up review.

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.