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 World Medical Association approved the latest revision of the Declaration of Helsinki on October 19， 2024， which was revised again after 11 years. As the international ethical principles for medical research involving research participants worldwide， this revision aims to respond to the dynamic and rapidly changing research environment and to ensure its relevance. The main contents of this revision include changing subjects to research participants as partners； adding other researchers as the implementing subjects and requiring individuals， teams， and organizations to comply； adding social value， always for the purpose of improving individual and public health； requiring free and full informed consent and maintaining the autonomy of research participants； advocating fair distribution and encouraging community participation； responsibly integrating vulnerable individuals， groups and communities； supporting the maintenance of independent review and authority， and clarifying the dual ethical review of international collaborative research； strengthening the supervision of biological samples and data to prevent risks； emphasizing that the welfare of research participants should be continuously maintained after the end of the clinical trials； adding environmental sustainability and expanding the scope of attention； requiring scientific integrity and maintaining the research environment； demonstrating the scientific validity of research plans and avoiding research waste； adding ethical principles should be observed during public health emergencies； using placebos cautiously and avoiding abuse； clarifying the conditions for the use of unproven interventions. To implement the revised contents of the Declaration of Helsinki， measures that could be taken include applying to all human-related research to protect research participants； centering on patients to ensure that research meets patients’ needs； implementing responsible inclusion through the collaboration of all parties； strictly supervising biological samples and data to protect privacy and maintain sustainable and healthy development； strengthening the supervision of the use of unproven interventions to safeguard the long-term interests of patients； continuously constructing ethics committees and embracing the support of artificial intelligence； standardizing effective informed consent and implementing the principles of freedom and adequacy. The Declaration of Helsinki， which aims to promote and ensure respect and protection of participants in a rapidly innovating medical research ecosystem， will continue to face revisions brought about by new challenges in the future.

Non-human primates are the closest relatives of human beings and possess similar morphological， anatomical， physiological， and behavioral characteristics， making them indispensable in fields such as neuroscience， reproduction， infectious diseases， and drug research and development. Currently， the restrictions on using non-human primates in experiments are becoming increasingly stringent in Europe and the United States. These experiments have ethical particularities that are different from those involving ordinary animals， and they also pose ethical challenges such as lack of necessity assessment， no unified assessment standards， and ethical dumping hazards. Supervision and ethical review should be strengthened. The key points of their ethical review include the necessity of the experiments， the assessment of the harm-benefit ratio， and the implementation of the “3R” principles.

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 revised content of the 2024 version of the Helsinki Declaration on vulnerability and the responsible inclusion of vulnerable participants, and to provide suggestions for improving regulations and ethics review in China. Methods:We analyzed the requirements of the Declaration of Helsinki and the preconditions for the inclusion of vulnerable groups, sorted out the international ethical principle and the relevant vulnerability provisions of China's laws and regulations, and proposed feasible recommendations for the inclusion and protection of vulnerable participants in China.Results:The Helsinki Declaration had been revised many times to involve the inclusion and protection of vulnerable participants, especially the Helsinki Declaration in 2024 for the first time proposed that vulnerability may originate from fixed or situational and dynamic factors, and vulnerability was no longer applicable to the traditional entire vulnerable group, and stipulated the prerequisites for the inclusion of vulnerable participants, because paying attention to " vulnerable groups" would affect the judgment of individual vulnerability, and should focus on the views and priorities of vulnerable individuals. Investigators and ethics committees should strengthen the identification and protection of vulnerable participants. The international ethical guidelines and China′s regulations had content on vulnerability, but there was a lack of consensus on the inclusion and protection of vulnerable participants. Conclusions:Feasible recommendations for the inclusion and protection of vulnerable participants in China include improving the relevant regulations on the inclusion of vulnerable participants in medical research, setting ethics review standards for vulnerable participants at the national level, strengthening the construction of ethics committees and training on the topic as well as clarifying key points of ethics review to maintain impartiality and avoid the misuse of vulnerable participants.

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.