The investigator-initiated trials （IIT）， as a widely existing form of clinical research both domestically and internationally， have attracted the attention of governments around the world due to the potential legal risks and issues they may cause， and the trend of legal supervision has gradually strengthened. The legal regulation of IIT in China is still in its early stages， with numerous legal issues that need to be clarified and sorted out. Based on the domestic and international legal reviews of IIT， this paper systematically sorted out the current situation of legal supervision of IIT in China and examined the existing issues， including weak legislative rules， incomplete regulatory systems， imperfect protection rules for research participants and informed consent systems， inadequate regulation of conflicts of interest management， and lax legal supervision of ethical review. Furthermore， this paper proposed suggestions for legal regulation of IIT from three perspectives， including strengthening legislation and emphasizing regulation， improving the mechanism for protecting research participants’ rights and interests， and balancing the legalization of IIT and the scientific development of clinical research， with a view to providing references for legal regulatory paths of IIT in China.

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.

To further standardize the ethical review of life science and medical research involving humans,the National Health Commission,the Ministry of Education,the Ministry of Science and Technology,and the State Administration of Traditional Chinese Medicine jointly issued the Measures of the Ethical Review of Life Science and Medical Research Involving Humans in 2023.The provisions concerning research related to health information data within it include:emphasizing the protection of personal information and privacy rights,personal information can only be collected,stored,and used under the premise that research participants know and permit,and must not be disclosed to third-party without the authorization of research participants;the ethical committee should focus on reviewing the adequacy of confidentiality measures of personal information;for research that provides information and data or cooperation with external organizations,it is necessary to fully understand the research,conduct a full ethical review,and clarify the use,processing,and disposal after completion of information data through an agreement.The research institutions should improve the information data governance and supervision system in conjunction with the key points of information data management in the new regulations.The initial ethical review should focus on the risk-benefit ratio of the research,the reasonableness of the informed consent procedure,the feasibility of the opt-out procedure,the protection measures for the privacy of the research participants,and the data management capability of the research team.The knowledge training of researchers should be strengthened,policy advisory services should be provided for them,and even a unified information data management platform should be built for them from the overall level of research institutions.The ethical follow-up review emphasizes whether the researchers continue to protect the participant's right to independent information or personal information,and privacy.It is believed that through a series of governance measures,the health information data of research participants in China will be better protected,thus safeguarding their legitimate rights and interests.

The seventh article of Measures for the Ethical Review of Biomedical Research Involving Humans (2016) stipulated that medical and health institutions without an ethics committee shall not carry out biomedical research involving Humans. The Opinions on Strengthening the Governance of Ethics in Science and Technology, issued in March 2022, clearly stated that the institutions that do not meet the conditions for establishing a scientific and technological ethics (review) committee should entrust other institutions to conduct the review. The fourteenth article of Measures for Ethical Review of Life Science and Medical Research Involving Humans (2023) proposes that if an institution, which carries out life science and medical research involving humans, has not established an ethics committee or its ethics committee is not competent for ethics review, it can entrust a competent ethics committee or regional ethics committee in writing to carry out ethical review. Most medical institutions at or above the second level in China have set up ethics committees. While most universities and colleges, scientific research institutions, enterprises and grass-roots medical and health institutions have not set up ethics committees, which lack a working system to protect the safety and interests of the participants, and is difficult to conduct life sciences and medical research involving humans. At present, there is a need for some research institutions that do not have the conditions to establish ethics committees to entrust their projects of life science and medical research involving humans to other institutions for ethical review. The entrusted review is still in the exploratory stage, and there is no relevant specification. The hasty implementation of entrusted review may not achieve the goal of effectively protecting the safety and interests of the participants, and even cause legal disputes. Based on the thematic discussion, with reference to the relevant laws and regulations, departmental rules, ethical standards, and the experience of the ethics committees of some domestic institutions in implementing the entrusted review, the guideline was formulated for the reference of the current entrusted review to ensure the safety and interests of the participants.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

Objective: To assess the differences between ultrasound cardiac output monitor (USCOM) and thermodilution (TD) systematically in cardiac function monitoring of critically ill patients. Methods: The Chinese and English literatures about the clinical trials which using USCOM and TD to monitor cardiac function published in CNKI, Wanfang database, China biomedical literature database, VIP database, China Clinical Trial Registration Center, PubMed, Embase and Cochrane Library were searched by computer from the establishment to December 2018. Some indicators, like cardiac output (CO), cardiac index (CI), stroke volume (SV) and other parameters were used to evaluate cardiac function. Literature search, quality evaluation and data extraction were conducted independently by two authors. The tailored Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used for literature quality evaluation. EndNote X6 was used for literature screening and management. RevMan 5.3 was used for Meta-analysis. Funnel chart analysis was used for publication bias. Results: A total of 26 studies involving 772 patients were included. Among them, there were 5 literatures found that the agreements of cardiac function between the USCOM and TD methods were poor. Meta-analysis showed that there was no significant difference between the two methods in CO and CI monitoring [CO: mean difference (MD) = -0.06, 95% confidence interval (95%CI) was -0.17 to 0.05, P = 0.31; CI: MD = -0.04, 95%CI was -0.13 to 0.05, P = 0.38]. Subgroup analysis of different TD methods [pulmonary artery catheter (PAC), pulse indicator continuous cardiac output (PiCCO)] and different windows of USCOM ultrasonic probe [aorta (AA), pulmonary artery (PA)] in CO monitoring was not shown significant difference yet (PAC: MD = -0.07, 95%CI was -0.18 to 0.04, P = 0.23; PiCCO: MD = 0.09, 95%CI was -0.31 to 0.50, P = 0.65; AA windows: MD = -0.14, 95%CI was -0.31 to 0.02, P = 0.09; PA windows: MD = -0.00, 95%CI was -0.15 to 0.14, P = 0.95; AA/PA windows: MD = 0.23, 95%CI was -0.40 to 0.86, P = 0.47). However, the difference in SV was statistically significant between the USCOM and TD method (MD = 1.48, 95%CI was 0.04 to 2.92, P = 0.04). Funnel chart showed that the literature distribution of CO and CI monitoring were basically symmetrical, indicating that the bias of literature publication is small. Conclusion USCOM has good consistency with TD method in monitoring the cardiac function parameters of CO and CI, and different windows of ultrasonic probe of USCOM have no significant influence on the monitoring results, but there is significant difference in the consistency of the two methods in SV monitoring.

OBJECTIVE: To assess the differences between ultrasound cardiac output monitor (USCOM) and thermodilution (TD) systematically in cardiac function monitoring of critically ill patients. METHODS: The Chinese and English literatures about the clinical trials which using USCOM and TD to monitor cardiac function published in CNKI, Wanfang database, China biomedical literature database, VIP database, China Clinical Trial Registration Center, PubMed, Embase and Cochrane Library were searched by computer from the establishment to December 2018. Some indicators, like cardiac output (CO), cardiac index (CI), stroke volume (SV) and other parameters were used to evaluate cardiac function. Literature search, quality evaluation and data extraction were conducted independently by two authors. The tailored Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used for literature quality evaluation. EndNote X6 was used for literature screening and management. RevMan 5.3 was used for Meta-analysis. Funnel chart analysis was used for publication bias. RESULTS: A total of 26 studies involving 772 patients were included. Among them, there were 5 literatures found that the agreements of cardiac function between the USCOM and TD methods were poor. Meta-analysis showed that there was no significant difference between the two methods in CO and CI monitoring [CO: mean difference (MD) = -0.06, 95% confidence interval (95%CI) was -0.17 to 0.05, P = 0.31; CI: MD = -0.04, 95%CI was -0.13 to 0.05, P = 0.38]. Subgroup analysis of different TD methods [pulmonary artery catheter (PAC), pulse indicator continuous cardiac output (PiCCO)] and different windows of USCOM ultrasonic probe [aorta (AA), pulmonary artery (PA)] in CO monitoring was not shown significant difference yet (PAC: MD = -0.07, 95%CI was -0.18 to 0.04, P = 0.23; PiCCO: MD = 0.09, 95%CI was -0.31 to 0.50, P = 0.65; AA windows: MD = -0.14, 95%CI was -0.31 to 0.02, P = 0.09; PA windows: MD = -0.00, 95%CI was -0.15 to 0.14, P = 0.95; AA/PA windows: MD = 0.23, 95%CI was -0.40 to 0.86, P = 0.47). However, the difference in SV was statistically significant between the USCOM and TD method (MD = 1.48, 95%CI was 0.04 to 2.92, P = 0.04). Funnel chart showed that the literature distribution of CO and CI monitoring were basically symmetrical, indicating that the bias of literature publication is small. CONCLUSIONS USCOM has good consistency with TD method in monitoring the cardiac function parameters of CO and CI, and different windows of ultrasonic probe of USCOM have no significant influence on the monitoring results, but there is significant difference in the consistency of the two methods in SV monitoring.
Cardiac Output ; China ; Humans ; Monitoring, Physiologic ; Thermodilution ; Ultrasonography

Objective:To summarize the existing problems and countermeasures of informed consent when children,one of the vulnerable groups in China,participate in clinical research,and further to provide reference for ethical review.Methods:We reviewed and comprehensively analyzed the domestic literatures that involved children and required informed consent.Results:Aiming at the unique physiological and psychological cognitive characteristics of children,this paper expounded the rationality of children's participation in clinical research and the timing of choice.It emphasized the existing problems in the process of informed consent such as inadequate informing,verbal acknowledgement,too long or too short time informed by the doctor-in-charge,as well as overspecialization of informed consent,inductive language,not describing potential risks and other incomplete information disclosure.According to these problems,the paper put forward some countermeasures.Conclusions:Informed consent of children's participation in clinical research should follow the general principles,consider children's characteristics,respect their willingness,and avoid unnecessary harm.

Objective:To summarize the notice of informed consent about gene information detection,and to provide a reference for ethical review of informed consent in clinical research involved gene information detection.Methods:We researched domestic and foreign literatures about gene information detection involved informed consent and comprehensively analyzed them.Results:Gene information detection caused the individual,family,and social aspects of privacy issues,and the right not to know gene information detection had been widely recognized.Informed consent was adopted in informed consent,which not only was respect for personal dignity and autonomy,but also was conducive to the effective use of gene resources.It should construct reasonable procedural system in le gal protection,guarantee the voluntary and authenticity of consent,and put it into practice.Based on the establishment of the right not to know,the Chinese law should also prohibit the implementation of gene detection or provision of gene information put forward by employers and insurance companies.In addition,it is strictly prohibited to detect infant incurable disease genes.Conclusion:In the ethical review of clinical research,when the conflict arises,it is necessary to design informed consent to resolve the conflict between the individuals' rights not to know and their personal health benefits,and to establish reasonable procedures in legislation to ensure the implementation of informed consent.