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.

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.

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.

Portal vein tumor thrombus (PVTT) is one of the common complications of hepatocellular carcinoma (HCC) with a high mortality rate. Several studies have shown that active implementation of effective treatment can significantly improve the quality of life and prolong survival of HCC patients with PVTT. In recent years, with the continuous development of molecular biology and molecular immunology, the treatment of advanced liver cancer has shifted from single agent to combination therapy, among which, the combination of immune checkpoint inhibitors and other systemic or local therapies has attracted much attention. This treatment strategy has shown good efficacy in some large-scale clinical trials. With the deepening of relevant research, it is believed that this treatment scheme will bring more hope and opportunities to such patients.

Objective:To investigate the effect of fat mass index (FMI) on early recovery after total knee arthroplasty (TKA).Methods:Patients who underwent primary unilateral TKA in Xi'an Honghui Hospital from July 2020 to July 2021 were retrospectively analyzed. The preoperative body composition was measured by dual energy X-ray absorptiometry and the FMI was calculated. Patients were divided into normal group (male: 3.0-6.0 kg/m 2; female: 5.0-9.0 kg/m 2), overweight group (male: 6.1-9.0 kg/m 2; female: 9.1-13.0 kg/m 2), and obese group (male: >9 kg/m 2; female: >13 kg/m 2) according to level of FMI, and the operation time, blood loss, and incidence of postoperative complications were collected. Multifactorial analysis of the effect of FMI on early recovery after TKA was performed using a generalized linear model. Draw the receiver operating characteristics (ROC) curve of BMI and FMI on the predicted effect of postoperative Western Ontario and McMaster Universities (WOMAC) osteoarthritis index scores and Knee Society Score (KSS) to compare the effect of FMI with BMI on early recovery after TKA. Results:A total of 100 patients were included in the study, 24 males and 76 females, aged 65.0±8.2 years (range, 42-81 years). There were 15 cases in normal group, 55 cases in overweight group and 30 cases in obese group. All patients successfully completed the operation and were followed up for 3.15±0.72 months (range, 2.8-3.2 months). The WOMAC scores of the obese group at 2 weeks, 1 and 2 months postoperative were 34.57±3.68, 22.03±2.79, and 15.77±2.96, which were greater than those of the normal group (28.73 ±2.58, 19.07±2.71, 12.27±3.10), as well as the overweight group (30.05±4.09, 19.33±2.42, 14.84±2.42), with statistically significant differences ( P<0.05). The KSS scores of the obese group at postoperative 1 and 2 months were 68.83±5.52 and 81.17±4.49, which were lower than those of the normal group (77.33±5.63, 87.33±4.17), as well as the overweight group (72.64±5.43, 83.73 ±5.02), with statistically significant differences ( P<0.05). The WOMAC score, KSS score, and postoperative complications at 2 months postoperatively were selected as outcome indicators to plot the ROC curve, and the ROC curve for the WOMAC score at 2 months postoperatively showed an area under the curve corresponding to FMI of 0.744 (95% CI: 0.54, 0.82), which was greater than that of BMI [0.624 (95% CI: 0.51, 0.74)], and the difference was statistically significant ( Z=2.19, P=0.021). The ROC curve for the KSS score at 2 months postoperatively showed an area under the curve corresponding to FMI of 0.718 (95% CI: 0.62, 0.82), which was greater than that of BMI [0.612 (95% CI: 0.52, 0.74)], with a statistically significant difference ( Z=2.58, P=0.016). The ROC curve for postoperative complications showed an area under the curve of 0.639 (95% CI: 0.41, 0.88) for FMI and 0.605 (95% CI: 0.37, 0.84) for BMI, with no statistically significant difference ( Z=0.48, P=0.632). Conclusion:The greater the FMI the poorer the early functional recovery after initial TKA, and FMI is more valuable than BMI in predicting the early functional recovery.

In February 2023, the National Health Commission, together with the Ministry of Science and Technology, the Ministry of Education, and the State Administration of Traditional Chinese Medicine issued the Ethical Review Measures for Life Science and Medical Research Involving Humans, which emphasizes that research participants involving vulnerable groups such as children, intellectual disabilities, and mental disabilities should be given special protection. This paper expounded the current situation of protecting vulnerable groups from six aspects: inadequate protection of vulnerable groups by relevant laws and regulations, unclear definition of vulnerable groups, insufficient supervision by relevant departments, insufficient review ability of ethics committee to satisfy the protection of vulnerable groups, difficulty in fair inclusion of vulnerable groups, and the need to improve the ethical awareness of researchers and vulnerable groups. This paper also analyzed the new requirements for the protection of vulnerable groups in the Ethical Review Measures for Life Science and Medical Research Involving Humans from the following three aspects: expanding attention to potentially vulnerable research participants, paying more attention to the consent of research participants without or with limited capacity for civil conduct, and re-informed consent after the improvement of civil capacity level. Finally, suggestions on strengthening the protection of vulnerable groups were put forward from six aspects: improving the relevant legal system, clarifying the category of vulnerable groups, strengthening the implementation by regulatory departments, establishing a research participant protection system by research institutions, improving the ethical review capacity of ethics committees, formulating review guidelines by industry associations, and strengthening the education and training of all parties, so as to minimize the risk of vulnerable groups participating in clinical research and boost the quality and speed of clinical research in China.

Relying only on the ethics committee to protect subjects is not enough, and the construction of the subject protection system is an inevitable trend for the protection of subjects’ rights. This paper elaborated on the current situation of Chinese subject protection system from four aspects: the lack of laws and regulations and administrative supervision, the insufficient attention of hospitals, poor construction of the subject protection system, and the absence of responsibilities of relevant personnel. Then this paper put forward countermeasures from three aspects: improving laws and regulations and strengthening supervision, mobilizing relevant departments to participate, and strengthening relevant training, in order to standardize the construction of the subject protection system and promote the development of the subject protection work.

Posterior internuclear ophthalmoplegia is a rare sign of pons infarction.Due to its mild clinical symptoms,it is easily misdiagnosed.In this article,we report a case of posterior internuclear ophthalmoplegia caused by pons infarction,discuss the causes of misdiagnosis and hope to attract the attention of doctors.By analyzing the clinical features of the case and reviewing the literatures,we try to differentiate the disease from multiple sclerosis,pons tumors and other diseases.The diagnosis was confirmed with thorough physical examination,laboratory test and imaging examination.Posterior internuclear ophthalmoplegia is a sign of pons infarction.

Objective:To investigate the pathogenic bacteria distribution and risk factors of pulmonary infection after tracheotomy in patients with stroke coma,and to put forward preventive measures.Methods:96 patients with stroke coma from January 2016 to February 2017 in our hospital were retrospectively analyzed.The incidence of pulmonary infection and distribution of pathogenic bacteria of patients with stroke coma were analyzed.At the same time,the risk factors of pulmonary infection were analyzed by single factor and multiple factors logistic regression analysis,and corresponding preventive measures were put forward.Results:The incidence of pulmonary infection after tracheotomy in 96 patients with stroke coma was 48.96％ (47/96).A total of 104 pathogens were isolated and cultured,including gram negative bacteria 69 strains (66.35％),gram positive bacteria 20 strains (19.23％) and fungus 15 strains (14.42％).Single factor regression analysis results showed that pulmonary infection after tracheotomy in patients with stroke coma was closely related with age,basic diseases,time of tracheotomy,and bed time,use of broad-spectrum antibiotics,smoking history,artificial airway,times of sputum suction and inhalation(P＜0.05),and it was not related to the patient's gender,weight,stroke type (P＞0.05).Multivariate logistic regression analysis showed that age 45 years old,complicated with basic disease,time oftracheotomy 5 d,use of broad-spectrum antibiotics,smoking history and the establishment of artificial airway were risk factors of pulmonary infection after tmcheotomy in patients with stroke coma (P＜0.05).ROC analysis results showed that the critical point (threshold C) oftmcheotomy time was 4.3 days,and the sensitivity and specificity were 0.851 and 0.918 respectively.Conclusion:The main pathogenic bacteria of pulmonary infection after tracheotomy in patients with stroke coma is gram-negative bacteria,age 45 years old,complicated with basic disease,time of tmcheotomy 5d,use of broad-spectrum antibiotics,smoking history and the establishment of artificial airway can lead to pulmonary infection after tracheotomy in patients with stroke coma,and the risk of pulmonary infection in patients with stroke coma will increase considerably after the time of tracheotomy for more than 4.3 days.Targeted measures should be taken to reduce the risk of pulmonary infection according to pathogenic features and risk factors.

Objective: The aim of this study was to investigate whether genetic variability in the protocadherin 15 (PCDH15) gene may correspond with increased susceptibility to noise-induced hearing loss (NIHL) in a Chinese population. Methods: A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In this study, 394 cases who had an average hearing threshold of more than 40 dB (A) in high frequency were defined as the case group, and 721 controls who had an average hearing threshold of less than 35 dB (A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. A questionnaire was completed by participants and a physical test was also conducted. SNP genotyping was performed using the SNPscan^TM Kit. Multivariate unconditional logistic regression additive models were used to analyze the genotypes in different groups, and the association with NIHL. Unconditional logistic regression models were used to assess the associations between the genotypes and NIHL. Results: The average age of study participants was (40.5±8.3) years and the median number of noise-exposed working years M (P₂₅, P₇₅) was 21.1 (9.1, 27.3). The range of noise exposed levels and the levels of cumulative noise exposure (CNE) were 80.1- 98.8 dB(A) and 86.6- 111.2 dB(A), respectively. Only the distribution of the genotypes (TT/CC/CT) of rs11004085 in the PCDH15 gene showed a significant difference between the case and control groups (P=0.049). In the case group, the distribution was 370 (93.9%), 24 (6.1%) and 0; in the control group, the distribution was 694 (96.3%), 23 (3.2%) and 1 (0.1% ). After smoking, drinking, hypertension, height and CNE adjustment, compared with the TT genotype individuals with the CC/CT genotype had a 1.90-fold increased risk of NIHL (95% CI: 1.06- 3.40). After stratified these data by the noise exposure level or CNE when the noise exposure level was>85 dB (A), compared with cases with the AA genotype of rs10825113, individuals with the GA/GG genotype had a 2.63-fold increased risk of NIHL (95% CI: 1.12- 6.14). When the CNE was ≤ 98 dB(A), compared with cases with the TT genotype of rs11004085, individuals with the CC/CT genotype had a 2.96-fold increased risk of NIHL (95% CI: 1.33- 6.56). However, these differences were not significant after Bonferroni correction had been applied. Conclusions The results confirmed that genetic variation within the PCDH15 gene may affect the susceptibility to NIHL.