In recent years,with the gradual maturity of achievable remote collection of digital health technology,more and more clinical research have applied this technology to improve the quality of data collection and reduce the burden on subjects.However,its technological characteristics of detachment from the diagnostic and treatment environment and real-time transmission of sensitive information also pose corresponding risks to the protection of subjects'rights and interests and data standardization management,among which personal information protection and data control permissions are more prominent issues.Based on risk analysis and regulatory review,this paper explored the responsibilities of multiple parties,including the sponsors,researchers,clinical trial institutions,and ethics committee,as well as proposed five elements of special concern for ethical review,with a view to providing a reference for promoting the standardized development of digital health technology in clinical research.

Objective To investigate the correlation between pericarotid fat density(PFD)and carotid plaque CT vulnerability characteristics.Methods The clinical and imaging data of 78 patients were analyzed retrospectively.PFD and subcutaneous neck fat density(SNFD),as well as plaque density,degree of lumen stenosis,and maximum plaque thickness were measured on picture archiving and communication system(PACS),and PFD/SNFD ratio was calculated.The plaques were divided into 4 subgroups according to their composition,namely fatty plaque group,fibrous plaque group,calcified plaque group and mixed plaque group.The groups were divided into no/mild-to-moderate stenosis group and severe stenosis/complete occlusion group according to the degree of stenosis,and the differences between groups were compared for clinical indices,PFD,SNFD and PFD/SNFD ratio,respectively.Results The PFD/SNFD ratio[0.54(0.32,0.72)]in the fatty plaque group was lower than that in the calcified plaque group[0.74(0.56,0.96)],with a statistically significant difference(P=0.005).The PFD/SNFD ratio in the severe stenosis/complete occlusion group(0.51±0.29)was lower than that in the no/mild-to-moderate stenosis group(0.67±0.27)(P=0.001),and the PFD in the severe stenosis/complete occlusion group[-39.75(-61.13,-24.00)]was higher than that in the no/mild-to-moderate stenosis group[-61.75(-72.00,-45.38)](P＜0.001).Conclusion PFD,PFD/SNFD ratio are correlated with carotid plaque vulnerability.

Objective:To examined the role of copper starvation in oral squamous cell carcinoma(OSCC),along with the molecular functions and mechanisms of SLC31A1 in these cells.Methods:Initially,SLC31A1 was silenced to induce a copper starvation environment.Sub-sequently,we evaluated the effects of copper starvation on oral squamous cell carcinoma cells using the CCK-8 assay,cell scratch assay,and subcutaneous tumor formation in nude mice.In addition,changes in autophagy and EZH2 expression levels in oral squamous cell carcinoma cells were detected after SLC31A1 silencing.Lactate dehydrogenase activity was assayed to determine its impact on natural killer(NK)cell cytotoxicity after SLC31A1 silencing.Results:Silencing of SLC31A1 significantly inhibited the proliferation,migration,and subcutaneous tu-mor formation ability of oral squamous cell carcinoma cells.Furthermore,silencing SLC31A1 mediated EZH2 degradation and increased NK cell infiltration.Conclusions:Copper starvation can regulate the proliferation,migration,and subcutaneous tumor formation ability of oral squamous cell carcinoma and increase NK cell infiltration by modulating EZH2 expression.

Objective To adapt to the requirements of medical technology innovation under the new situation.To explore the establishment of a scientific,standardized,and reasonable management institution and system.It aims to actively promote the development of Investigator Initiate Trials(IITs)in medical and health institutions.Methods By conducting a literature review,policy interpretation,and examing work practices,this study identified the pain points and difficulties in IIT management.It sorted out the core requirements and elements needed for effective IIT management and proposed measures.Results The study proposed the development of five support systems for IIT management.A functional responsibility system for implementing classified and tiered management of IITs with clear delineation of responsibilities and authority;A quality supervision system that introduces a third-party co-management mechanism to fill the gaps of IIT quality management in the three-level quality control system;A fund support system that reduces or waives the hospital management fees for IITs,and incorporate the IIT undertaking into the annual evaluation metrics for optimized SMO;A collaborative innovation system that connect with external enterprises and coordinates internal departments to jointly promote the efficient operation of IITs;A risk early warning system that establishes IIT risk assessment criteria and conducts real-time dynamic supervision,strengthening IIT data management,and ensuring IIT data security.Conclusions Currently,IIT management generally lacks sufficient attention in China,and there is no complete framework or practice.By constructing the five IIT system construction scheme.It is conducive to optimizing the process,improving efficiency,ensuring quality and reducing risk,which has certain reference significance for the improvement and development of IIT management.

Objective:To investigate the correlation between stress hyperglycemia ratio (SHR) and poor outcome of successful recanalization after endovascular treatment in patients with acute ischemic stroke.Methods:From January 2019 to October 2022, patients with acute ischemic stroke received endovascular treatment and successful recanalization in the Second People’s Hospital of Lianyungang were included retrospectively. SHR was defined as the fasting blood sugar and glycosylated hemoglobin ratio. At 90 d after procedure, the outcome of patients was evaluated using the modified Rankin Scale score. 0-3 was defined as good outcome, and >3 was defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent risk factor for poor outcome. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SHR for 90 d poor outcome in patients with successful recanalization after endovascular treatment.Results:A total of 159 patients were enrolled, including 98 males (61.6%), aged 69.8±8.9 years old. The baseline National Institutes of Health Stroke Scale (NIHSS) score was 12.6±4.3, and SHR was 1.17±0.46. One hundred and five patients (66.0%) had good outcome, while 54 (34.0%) had poor outcome. There were statistically significant differences in SHR, fasting blood glucose, glycosylated hemoglobin, baseline NIHSS score and the proportion of patients with poor collateral circulation and symptomatic intracranial hemorrhage between the poor outcome group and the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that SHR was an independent predictor of poor outcome (odds ratio 2.254, 95% confidence interval 1.136-4.278; P<0.001). The ROC curve analysis showed that the area under the curve of SHR for predicting poor outcome was 0.726 (95% confidence interval 0.648-0.804; P<0.001), which was higher than fasting blood glucose and glycosylated hemoglobin. The optimal cutoff value for SHR was 1.21, and the sensitivity and specificity for predicting poor outcomes were 66.23% and 75.82%, respectively. Conclusion:SHR is associated with the poor outcome of successful recanalization after endovascular treatment in patients with acute ischemic stroke and can be used as a potential predictor.

Ethical review runs through the whole process of drug clinical trials, and is a critical step to ensure the rights and interests of subjects. This paper analyzed and discussed the role and positioning of ethical review in new drug clinical trials, cleared the principles of ethical review, identified the responsibilities of ethical review, and clarified the authority of ethical review approval documents. The ethical review should primarily focus on the ethics of the clinical trials, not replace other professional institutions to review the clinical trials’ legality and scientific nature. Ethical approval is only one of the necessary conditions for conducting clinical trials, not the only factor. It is recommended to strengthen the publicity and popularization of scientific and technological ethics awareness, improve the clinical trial approval mechanism, and optimize the phrasing of ethical review approval documents. It is warranted to further optimize the quality of ethical review, improve the construction of ethical review system, ultimately achieve the unity of promoting innovation and preventing risks, so as to effectively realize the benign interaction between high-quality development of scientific and technological innovation and high-level safety.

From the perspective of medical institutions, this paper sorted out the contents of Article 32 of the Measures for Ethical Review of Life Sciences and Medical Research Involving Human regarding "exemption from ethical review". At the same time, combined with domestic and foreign regulations, this paper deeply considered and analyzed the applicable premise and special circumstances of the provisions from the implementation level, and then put forward suggestions from the perspective of practical operation of medical institutions, with a view to providing some practical guidance and reference for ethical practitioners of medical institutions.

From the perspective of medical institutions, this paper sorted out the background of the promulgation and important changes of Measures for Ethical Review of Life Science and Medical Research Involving Humans, and summarized the changes that may significantly affect the ethical review of medical institutions. It involved terminology changes and expansion of the scope of ethic review, clarification of the responsibilities and independence of the ethics committee, the refinement of the ethical review process, the emphasis on the protection of personal information and the rights and interests of subjects, and first proposal to exempt from ethical review. In addition, based on the concept of strengthening the ethical governance of science and technology in the new version of regulations, this paper shared the consideration on the governance of ethical review within medical institutions, including safeguarding the dignity and rights of subject, clarifying the role and position of ethical review, exempting the implementation of ethical review, and managing entrusted ethical review. With a view to providing a certain reference for the ethics practitioners and researchers in various medical institutions.

Objective:To evaluate the effects of GSK484 on ventilator-induced lung injury (VILI) and neutrophil extracelluar traps (NETs) in mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 5-6 weeks, weighing 15-20 g, were divided into 4 groups ( n=12 each) by a random number table method: spontaneous breathing group (group S), spontaneous breathing+ GSK484 intervention group (group SG), VILI group (group V), and VILI + GSK484 intervention group (group VG). The animals kept spontaneous breathing for 4 h after tracheal intubation in S and SG groups. The animals were mechanically ventilated for 4 h (tidal volume 30 ml/kg, respiratory rate 75 breaths/min, inspiratory/expiratory ratio 1∶2, positive end-expiratory pressure 0 mmHg, fraction of inspired oxygen 21%) in V and VG groups. At 3 days before developing the VILI model, GSK484 4 mg/kg was intraperitoneally injected once a day in SG and VG groups, while the equal volume of normal saline was given instead in S and V groups. Blood samples were collected from the abdominal aorta for blood gas analysis at 4 h of spontaneous breathing or mechanical ventilation, and PaO 2 was recorded. The mice were then sacrificed and bronchoalveolar lavage fluid (BALF) was collected and lung tissues were obtained for microscopic examination of the pathological changes (with a light microscope after HE staining) which were scored and for determination of wet to dry weight ratio (W/D ratio), concentrations of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) in BALF (by enzyme-linked immunosorbent assay), expression of peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), high mobility group box 1 (HMGB1) and citrullinated-histone 3 (Cit-H3) in lung tissues (by Western blot). Results:Compared with S and SG groups, the lung injury score and W/D ratio were significantly increased, PaO 2 was decreased, concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were increased, and the expression of PAD4, NE, HMGB1 and Cit-H3 in lung tissues was up-regulated in V and VG groups ( P<0.05). Compared with group V, the lung injury score and W/D ratio were significantly decreased, PaO 2 was increased, the concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were decreased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was down-regulated in group VG ( P<0.05). Conclusions:GSK484 can alleviate VILI in mice, and the mechanism is associated with inhibition of PAD4, reduction of the production of NETs and attenuation of inflammatory responses in lung tissues.

With the implementation of the national biomedical innovation strategy, new requirements for ethical review of clinical trials have been put forward, and more attention has been paid to the ethical pre-review. Based on the current situation of clinical trials and ethical review of new drugs in China, this paper discussed the concept, advantages and necessity of ethical pre-review, sorted out the problems and challenges in the implementation of ethical pre-review at this stage, and put forward the following suggestions on how to better implement ethical pre-review in clinical trials under the pharmaceutical innovation strategy: the complete definition of "ethical pre-review" should be made clearly; ethical review should be carried out on the basis of necessary reference; the scope of application of ethical pre-review should be clarified; after the ethical pre-review, the statement of the approval document should be standardized and accurate.