Conducting ethical review of investigator-initiated trials （IIT） is one of the important links to ensure the quality of research projects. Currently， the quality of ethical review for IIT projects is greatly influenced by the personal factors of committee members， which to some extent affects the ethical review committee’s judgments of research risks and benefits. Based on the previously developed Risk-Benefit Assessment Scale for Clinical Research， this paper established an ethical review decision-making pathway based on risk-benefit assessment， that is， proposed the “four-step method” for ethical review risk-benefit assessment， including evaluating the research benefits， assessing the research risks， constructing a risk-benefit matrix， and establishing an ethical review pathway. The “four-step method” helps to reduce the impact of committee members’ subjective/intuitive judgments on the quality of ethical review， assists in promoting the implementation of multi-center ethical review policy， narrows the gap in the quality of ethical review among different medical institutions， and provides clearer guidance for the risk judgments of scientific research management and ethical review departments.

This paper discussed the current education status on medical ethics and styles and the assessment condition in the examination of doctors' qualification， as well as the existing problems and potential solutions by reviewing domestic and foreign literature and summarizing the practice experience. Traditionally， medical ethics and styles have always been integrated into clinical medical practice in China. However， under the modern medical education system， it is challenged to integrate traditional education on medical ethics and styles with the rules of modern medical knowledge. By summarizing the education and assessment status of medical ethics and styles in the examination of doctors' qualification， it is found that the current examination is relatively poor in the evaluation content， and the way of evaluation is not diverse， with lack of curriculum of medical humanities. The solutions suggested are enriching relevant examination content， introducing more and comprehensive evaluation method， and establishing more medical humanities-related courses.

Objective:Using the established epilepsy patient database to validate the efficacy of the web-based epilepsy diagnosis and anti-seizure medications (ASM) selection tool, EpiPick, for domestic epilepsy patients.Methods:The retrospective collection of clinical data was conducted on patients aged 10 and above who were diagnosed with epilepsy at the Comprehensive Epilepsy Center of the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2020, with regular follow-up and complete information. According to the first ASM recommended by the EpiPick tool and whether they are consistent with the actual ASM used by patients, patients were divided into EpiPick group and clinical group to verify the effectiveness of the EpiPick tool in selecting ASM. The drug retention rate, Engel score, and cumulative probability of no consecutive episodes within 30 months after using the first ASM were compared between the 2 groups, and Kaplan-Meier survival curves were drawn. Finally, the diagnostic results provided by the EpiPick tool were compared with the actual types of epileptic seizures diagnosed clinically, and consistency tests were performed.Results:A total of 364 epilepsy patients were included, including 237 in the EpiPick group and 127 in the clinical group. The ASM retention rates of patients in the EpiPick group and clinical group were 67.9%(161/237) and 56.7%(72/127), respectively, with statistically significant differences (χ2=4.534, P=0.039). Grades Ⅰ, Ⅱ, Ⅲ and Ⅳ according to the Engel scores in the EpiPick group patients who took the first ASM after diagnosis accounted for 47.3%(112/237), 14.8%(35/237), 12.7%(30/237), and 25.3%(60/237), respectively, compared to the clinical group of 32.3%(41/127), 11.8%(15/127), 11.0%(14/127), and 44.9%(57/127), respectively. There was a statistically significant difference in Engel scores between the 2 groups (χ2=14.968, P=0.002). The cumulative seizure-free rates in the EpiPick group at the 1st, 6th, 12th, 30th month and above after starting the first ASM were 73.8%, 61.2%, 53.2%, and 50.6%, respectively, which in the clinical group were 52.0%, 44.1%, 40.2%, and 33.5%, respectively. The logrank test showed a statistically significant difference in the cumulative probability of consecutive seizure freedom between the 2 groups ( HR=0.644 ,95% CI 0.476-0.871 ,P<0.001). After grouping by seizure type [focal seizures (196 cases) and generalized seizures (168 cases)], the cumulative seizure-free rates at the 1st, 6th, 12th, 30th month and above after starting ASM were significantly higher in the EpiPick group than in the clinical group (comparison between the 2 groups in patients with focal seizures: HR=0.654, 95%CI 0.443-0.964, P=0.004; comparison between the 2 groups in patients with generalised seizures: HR=0.586, 95%CI 0.361-0.954, P=0.014). Among 364 patients, 293 cases were clinically diagnosed with seizure classification consistent with the classification results of EpiPick tool. Agreement between the algorithm and the experts in classifying generalized seizures was 83.9%(104/124), which in classifying focal seizures was 78.8%(189/240; Kappa=0.591, P<0.001). Conclusion:Web-based EpiPick tool is suitable to be used to select the first ASM, and is portable for Chinese non-epilepsy specialists to choose ASM for epilepsy patients.

Objective To investigate the correlations of serum calcium, 25-hydroxyvitamin D and uric acid levels with benign paroxysmal positional vertigo (BPPV). Methods A total of 96 patients with BPPV were enrolled in vertigo group and further divided into mild vertigo (30 cases), moderate vertigo (42 cases), and severe vertigo (24 cases) groups based on the severity of vertigo symptoms. Additionally, 63 healthy people undergoing physical examination without BPPV were recruited as control group. Serum calcium, 25-hydroxyvitamin D, and uric acid levels were compared among groups, and their correlations with the severity of vertigo in BPPV patients were analyzed. Follow-up was conducted for 3 months to record the recurrence rate of BPPV. Results The serum calcium and 25-hydroxyvitamin D levels in the moderate and severe vertigo groups were significantly lower, while uric acid levels, total score of Dizziness Handicap Inventory (DHI) as well as functional, emotional, and physical scores were significantly higher than those in the mild vertigo group and control group (P < 0.05). Moreover, the severe vertigo group exhibited lower serum calcium and 25-hydroxyvitamin D levels and higher uric acid level, DHI total score and functional, emotional, as well as physical scores (P < 0.05). No significant differences were observed in serum calcium, 25-hydroxyvitamin D, uric acid levels, or DHI scores between the mild vertigo group and the control group (P>0.05). The severity of vertigo in BPPV patients was negatively correlated with serum calcium (r=-0.557, P < 0.05) and 25-hydroxyvitamin D levels (r=-0.467, P < 0.05), and positively correlated with uric acid levels (r=0.504, P < 0.05). The 3-month recurrence rate of BPPV was 8.33%(8/96). Compared to patients with serum calcium ≥2.11 mmol/L, 25-hydroxyvitamin D ≥30 ng/mL, and uric acid ≤428 μmol/L, those with serum calcium < 2.11 mmol/L, 25-hydroxyvitamin D < 30 ng/mL, and uric acid >428 μmol/L had significantly higher BPPV recurrence rates (P < 0.05). Conclusion BPPV patients exhibit abnormally lower serum calcium and 25-hydroxyvitamin D levels and abnormally higher uric acid levels. The severity of vertigo in BPPV patients is negatively correlated with serum calcium and 25-hydroxyvitamin D levels and positively correlated with uric acid levels.

OBJECTIVE To analyze the influencing factors for the metabolism of voriconazole in adult patients， and to provide reference for the rational use of voriconazole in clinic. METHODS The clinical data of adult patients admitted in our hospital receiving voriconazole and therapeutic drug monitoring from April 2021 to March 2022 were collected. The trough concentration of voriconazole （c0） and plasma concentration of voriconazole-N-oxide concentration （cN） were determined， and voriconazole-to-voriconazole N-oxide concentration ratio （c0/cN） was calculated. Pearson’s correlation analysis was used to analyze the influencing factors for c0 and c0/cN of voriconazole. Multiple linear regression models were used to analyze the independent influencing factors for c0 and c0/cN of voriconazole. RESULTS The underlying diseases of the patients were mainly pneumonia， kidney disease and leukemia. The detected fungi were mainly Aspergillus， Candida and yeast-like fungi. Voriconazole was mainly administered by intravenous drip， especially in patients who used proton pump inhibitor in combination. The levels of C-reactive protein （CRP）， total bilirubin （TBIL）， direct bilirubin （DBIL） and indirect bilirubin （IBIL） were positively correlated with c0 of voriconazole， while platelet count and albumin levels were negatively correlated with voriconazole c0. The levels of CRP， TBIL and DBIL were positively correlated with c0/cN， while albumin levels were negatively correlated with c0/cN. Multiple linear regression analysis showed that the independent influencing factors of voriconazole c0 included the levels of CRP and IBIL， route of administration and dose of voriconazole， and the independent influencing factors of voriconazole c0/cN were the levels of CRP and DBIL and age. CONCLUSIONS The levels of CRP and IBIL， route of administration and dose of voriconazole are independent influencing factors of voriconazole c0； the levels of CRP and DBIL and age are independent influencing factors of voriconazole c0/cN. The influence of above indexes on the metabolism of voriconazole should be considered when using voriconazole clinically； and the route of administration and dose of voriconazole should be adjusted reasonably.

OBJECTIVE To establish a method for the determination of polymyxin B concentration in plasma and apply it to clinical practice. METHODS After precipitated with 5% trichloroacetic acid solution， using polymyxin E2 as internal standard， the concentrations of polymyxin B1 and B2 in plasma sample were determined by UPLC-MS/MS. The determination was performed on BEH C18 chromatographic column with water （0.1% formic acid）-acetonitrile （0.1% formic acid） as mobile phase （gradient elution） at the flow rate of 0.5 mL/min. The sample size was 10 µL. The detection was accomplished with electrospray ionization operated in positive ion scanning by multi-reaction monitoring mode. The ion pairs for quantitative analysis were m/z 603.2→101.2 （polymyxin B1）， m/z 595.7→101.1 （polymyxin B2） and m/z 578.5→101.1 （internal standard）. The plasma concentration of polymyxin B in 79 critically ill patients was measured by the above method， the occurrence of acute renal injury （AKI） was recorded and the relationship of polymyxin B concentration in plasma with AKI was analyzed. RESULTS The linear ranges of polymyxin B1 and polymyxin B2 were 200-20 000， 50-5 000 ng/mL （r＞0.995）， and the lower limits of quantification were 200 and 50 ng/mL， respectively. RSDs of intra‐day and inter‐day precision tests were not higher than 12.06%， the average extraction recovery was 103.04%-117.44%， and RSDs of matrix effect test and stability test were all not higher than 7.42%. Steady state trough and peak plasma concentration were （2.54±2.52） and （8.17±5.20） mg/L for 79 clinical patients using polymyxin B. Eighteen patients out of 27 included patients developed AKI， with an incidence of 66.67%. The peak concentration of polymyxin B of patients without AKI was significantly lower than that of patients with AKI （P＜0.05）， but there was no significant difference in the trough concentration between two groups （P＞0.05）. CONCLUSIONS The established UPLC-MS/MS has the advantages of simple operation and high sensitivity， and can be used to monitor the plasma concentration of polymyxin B in patients. The occurrence of AKI is correlated with the peak concentration of polymyxin B.

Objective: To explore the association between dietary inflammatory index (DII) and metabolic syndrome (MetS) and its components among children aged 6-14 years in Beijing, so as to provide a reference for preventing MetS. Methods: A cross sectional study was carried out in 2 086 records of 1 832 children from the 2017 and 2019 Nutrition and Health Surveillance in Primary and Secondary school students of Beijing (NHSPSB). Three day consecutive 24 hour dietary recalls combined with weighing household cooking oils and condiments were used to collect dietary intake and calculate DII. MetS was diagnosed according to "Definition and Suggestion on the Metabolic Syndrome of Chinese Children and Adolescent". The Generalized estimating equations (GEEs) models were used to analyze the association between DII and the presence of MetS and its components (abdominal obesity, high triglyceride, low high density lipoprotein cholesterol, hypertension, and hyperglycemia). Results: The mean DII score was (1.64±1.07) for the included children. No significant association was found between DII scores and the likelihood of MetS (per 1 point increment: OR =1.16, 95% CI =0.92-1.48, P >0.05). In terms of the components of MetS, DII scores were positively associated with the odds of high triglyceride (per 1 point increment: OR =1.17, 95% CI =1.01-1.36, P <0.05). There was no statistically significant difference in the association among different age groups ( P >0.05). No significant associations were observed between DII and other MetS components( P >0.05). Conclusion DII scores may not be correlated with the risk of MetS, but proinflammatory diet might increase the risk of high triglyceride. DII score in childhood should be emphasized to identify and prevent MetS as soon as possible.

Guaranteeing the rights and safety of subjects is an important responsibility of all participants in the medical devices clinical trial, including medical institutions, sponsors and researchers. The legal disputes caused by serious adverse events in the clinical trial of medical devices are characterized by complex legal relationships, great difficulty in handling, and many points of dispute. Based on a typical case of medical device clinical trials, this paper discussed the litigation subject qualification, the treatment of contract breach and tort in medical device clinical trial, analyzed the responsibility of different subjects, and provided constructive suggestions on the risk management of medical device clinical trial.

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 detect the characteristics of vascular remodeling after carotid balloon injury model in rats using ultrasound biomicroscopy(UBM), and to discuss the application value of UBM technique by comparing ultrasonic characteristics with histopathological results.Methods:Carotid balloon injury was performed in 10-week-old SD rats(11 female and 11 male) by 2F Fogarty balloon catheter. The left common carotid artery(CCA) was injured and the right side in the same animal was used as an uninjured control. Arterial structures and hemodynamics were evaluated pre-procedure and post-procedure at 7, 14 days.The intima-media thickness(IMT) inner diameter, outer diameter, lumen area, vessel area, peak systolic velocity, end diastolic velocity of CCA were measured by UBM, and the vascular resistance index, shear stress and blood flow were calculated to evaluate the vascular hemodynamics. The histological data were obtained by H&E staining in cross-sections at 14 days after balloon injury. The characteristics of arterial structure and hemodynamic changes at various time points were compared, the structural changes of CCA between injured and control side after injury were compared. The Spearman correlation and linear regression were used to test the correlation between ultrasonic and histological measurements 14 days after balloon injury.Results:①Compared with pre-procedure, the IMT at 14 days after balloon injury was increased, the inner diameter was decreased, the shear stress in ultrasound was increased(all P<0.05). H&E staining histological test showed that IMT and neointima area in male rats were larger than those of female rats (all P<0.001). ②After carotid balloon injury, the lumen area decreased, but the CCA underwent compensatory positive remodeling and the vessel area increased. ③Significant correlations were demonstrated between UBM and histology in IMT, inner diameter, outer diameter and vessel area of CCA( rs=0.819, 0.965, 0.896, 0.955; all P<0.001). The vessel area value measured by UBM was larger than that of histology( P=0.006). Conclusions:The CCA of rats can be showed clearly by UBM in males and females. The arterial structure cab be measured by UBM accurately with good correlation with histology, as did arterial hemodynamic parameters, which may be benefit for the study in carotid balloon injury model of rats.