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.

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 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.

It is worth pondering how to seek advantages and avoid disadvantages in stem cell clinical research and give full play to the advantages of technology for the benefit of mankind. Through the analysis of the status of stem cell clinical research, including technology and related management methods, proposed the main problems existing in stem cell research, such as the risks of technological uncertainty, ambiguity between research and treatment, over-treatment and technological innovation. Then this paper discussed the ethical and legal risks of stem cell clinical research in China, mainly related to the problems that the construction of laws and regulations is lagging behind, the regulatory challenges of administrative departments are large, the ethical awareness of researchers needs to be further improved, the principle of fairness and justice is not taken into account, the research platform construction of medical institutions is not in place and the protection system of subjects is imperfect, and the organization construction and review capacity of the ethics committee is still lacking.

Objective:To explore the relationship between the completion time of fluid resuscitation as well as negative fluid balance volumes and the prognosis of patients with septic shock, and to try to construct a prediction model based on the completion time of fluid resuscitation and negative fluid balance volumes, and to verify the predictive efficacy of the model on the prognosis of patients with septic shock.Methods:Patients with septic shock admitted to Wuxi People's Hospital from April 2020 to April 2023 were selected. The general data (gender, age, body mass index, infection site), pathological indicators on admission, the difference of acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) between admission and 24 hours after fluid resuscitation, the completion time of fluid resuscitation and negative fluid balance volume were recorded. Multivariate Logistic analysis was used to screen the influencing factors of the prognosis of patients with septic shock, and a nomogram model was established. Bootstrap method was used for internal validation of the model. The consistency index, calibration curve and receiver operator characteristic curve (ROC curve) were used to evaluate the accuracy and prediction efficiency of the model.Results:A total of 96 patients with septic shock were enrolled, 38 patients died and 58 patients survived at 28 days. Compared with the survival group, the difference of APACHEⅡscore, SOFA score, the proportion of fluid resuscitation completed within 1 to 3 hours, and the proportion of negative fluid balance volume -500 to -250 mL per day in the death group were lower, and the differences were statistically significant (all P < 0.05). Multivariate Logistic analysis showed that the completion time of fluid resuscitation was a risk factor for the prognosis of patients with septic shock [odds ratio ( OR) = 26.285, 95% confidence interval (95% CI) was 9.984-76.902, P < 0.05]. The difference of APACHEⅡscore ( OR = 0.045, 95% CI was 0.015-0.131), SOFA score ( OR = 0.056, 95% CI was 0.019-0.165) between admission and 24 hours after fluid resuscitation, and negative fluid balance volume ( OR = 0.043, 95% CI was 0.015-0.127) were protective factors for the prognosis of patients with septic shock (all P < 0.05). The model validation results showed that the consistency index was 0.681 (95% CI was 0.596-0.924), indicating good discrimination. The calibration curve showed that the calibration curve fitted well with the ideal curve. The ROC curve showed that the sensitivity of the nomogram model for predicting the death of patients with septic shock was 83.7%, the specificity was 97.2%, and the area under the ROC curve (AUC) was 0.931 (95% CI was 0.846-0.985), indicating that the model had good prediction efficiency. Conclusion:The completion time of fluid resuscitation and negative fluid balance volumes are related to the prognosis of septic shock patients, and the alignment diagram model improve the identification of the risk of death in septic shock patients.

Patient-centered clinical trials refer to clinical trials that take participant'needs as the starting point,regard participant as active participants,and take clinical values as the ultimate goals.This concept has become the core guiding ideology of current pharmaceutical research and development,and the model of the patient-centered clinical trial will gradually become the mainstream model of pharmaceutical research and development.Patient-centered clinical trials in China have challenges such as difficulty in changing the way of trial thinking and quality control,increased difficulty in participant'privacy protection,lack of training for all research parties,and unfair recruitment of research participants.Then suggestions were proposed for patient-centered clinical trials in China from three aspects,including relevant departments provide more policy support,sponsors and relevant third parties timely transform ideas of research and development,as well as researchers and research participants strengthen awareness.This paper also put forward the key points of ethical review of patient-centered clinical trials from 8 aspects,including the trial design that incorporated preference information on patients and took into account the assessment of clinical outcomes,protection of the safety and rights of research participants,recruitment based on the needs of research participants,acceptable informed consent,the rationality of selection of decentralssed clinical trials elements,privacy protection of research participants,training and education of researchers and research participants,and compensation and indemnity of research participants,so as to standardize the ethics review of patient-centered clinical trials and ensure the quality of patient-centered clinical trials.

Objective:This paper analyzed the current situation of clinical research continuing review in China, and puts forward countermeasures to strengthen continuing review in combination with the requirements of the Measures for the Ethical Review of Life Science and Medical Research Involving Humans, so as to provide a certain reference for standardizing the ethical continuing review of research institutions.Methods:Through literature research, this paper systematically sorted out the current situation of continuing review, and analyzed many problems and related reasons in the process of continuing review of clinical research in China based on the practical experience of ethical review.Results:The requirements for continuing review in the Measures for Ethical Review of Life Science and Medical Research Involving Humans included demphasizing the implementation of continuing review, the entrusted ethics committee should be responsible for continuing review, clarifying the responsibility for continuing review of cooperative research, clarifying the responsibility of participating research institutions for continuing review, and increasing the responsibility of the ethics committee to supervise the submission of continuing review. Countermeasures to strengthen continuing review included the health authorities urging research institutions to strengthen continuing review, research institutions to increase efforts to implement continuing review, establishing a standardized continuing review process, strengthening the ethics training of researchers and other relevant personnel, establishing a multi-channel communication and consultation method between the ethics committee and researchers, strengthening the review capacity of ethics committee members, allocating a corresponding number of ethics committee staff, and using information technology to improve quality and efficiency.Conclusions:Continuing review is indispensable in the whole process of research development, and all parties should take measures to ensure the quality and efficiency of continuing review, standardize continuing review, and promote the healthy development of life science and medical research.

Objective:To analyze the current situation of the archives management of ethics committees in China, combine the requirements of the Implementation Regulations of the Archives Law of the People′s Republic of China and the ethics review regulations, and propose countermeasures to strengthen the archives management of ethics committees, thereby further standardizing the archives management of ethics committees.Methods:Through the literature research method, this study systematically reviewed the current situation of the archives management of ethics committees and analyzed its problems and causes in China in combination with related practice experiences.Results:The requirements for ethics committee archives included supervision and management, the establishment of rules and regulations, personnel, site and environment, storage period, confidentiality, and information construction. Countermeasures to strengthen the archives management of ethics committees were suggested including strict daily supervision, strengthening management awareness, establishing and improving the scientific management system and standard operating procedures, setting up independent ethics committee offices and dedicated archives, strictly implementing the confidentiality system, strengthening information construction, and improving utilization rate.Conclusions:To better construct and manage ethics committee archives, a standardized archives management system should be established to effectively evaluate the quality of ethics review and ensure the proper functions of the ethics committee.