Background: and Purpose Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD). Methods: Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as ≤17 μmol/L and >17 μmol/L based on the biological relevance of Gilbert’s syndrome. Hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al. Results: This study included 3,061 participants, with a mean age of 61.2±6.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41–2.44, P<0.001; Rothwell: OR=1.84, 95% CI 1.43–2.38, P<0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45–2.36, P<0.001) in participants with TBIL ≤17 μmol/L but not in TBIL >17 μmol/L (P for interaction <0.05). Johnson–Neyman analyses showed cut-off concentrations of 22.3–22.4 μmol/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not. Conclusions Mildly elevated TBIL may modify the association between hypertension and CSVD.

With the rapid advancement of medical technology and the increasing complexity of clinical environments, competence in clinical ethical decision-making has become an indispensable core competency for exemplary physicians. However, traditional medical ethics education has long been confronted with the persistent challenges of theory-practice dissociation and the disconnect between pedagogical settings and clinical realities. Thus, how to construct a "Clinical Ethics" curriculum that aligns with the objectives of training high-caliber medical professionals has emerged as a critical and challenging issue in current medical education reform. To effectively address this challenge, the Office of Education at Peking University Third Hospital, since 2021, has assembled a multidisciplinary "Clinical Ethics" teaching and management team comprising faculty from Peking University School of Humanities and key clinical specialists from the hospital. In 2022, the "Clinical Ethics" elective course was formally launched for fourth-year students in the eight-year MD program who had completed coursework in "Medical Ethics" and organ-system-based curricula, with the aim of exploring and operationalizing a pre-clinical ethics education model tailored for senior medical students. The course employs a modular instructional design encompassing "theoretical review-case-based deliberation-clinical workshop", which effectively facilitates the deep integration of medical humanities with clinical practice.Following four years of iterative refinement through the "plan-act-observe-reflect" cycle, the course has demonstrated positive outcomes in enhancing students' ethical awareness and decision-making capabilities, and has preliminarily established a sustainable collaborative mechanism among the multidisciplinary faculty team. This article systematically delineates the course development background, pedagogical model and methodological innovations, and the multidisciplinary collaborative framework, alongside reflections and summaries based on implementation outcomes, with the intent of providing references for the future development of "Clinical Ethics" curricula.

Objective:To explore the gaze characteristics towards emotional portraits in children with attention deficit hyperactivity disorder(ADHD),in order to reveal their potential unique patterns of emotional cognition.Methods:A case-control design was employed,including 81 children diagnosed with the DSM-5 ADHD and 57 normal control(NC)children.Emotional images from the Chinese Children's Emotional Image Library were used as stimuli.The Tobii Pro X3-120 eye-tracking device was utilized to record fixation count(FC)and fixation duration percentage(FDP)under a free-viewing paradigm.Mixed-effects ANOVA was applied to explore the effects of group,gaze region(eyes and mouth),and emotional attributes on gaze characteristics,controlling for gen-der and age.Results:The FC and FDP of ADHD children were lower than those of NC children,particularly in the eye region of non-negative emotional images(P＜0.05).However,no significant differences were observed be-tween the two groups when viewing negative emotional images(sadness and anger)(P＞0.05).NC children ex-hibited a significant emotional bias effect in their gaze behavior towards emotional portraits(P＜0.05),whereas ADHD group showed only slight differences between non-negative emotional images(adjusted P＜0.05),indica-ting a weaker overall emotional attention bias.Conclusion:Children with ADHD display reduced attention to non-negative emotional expressions and a diminished emotional attention bias,suggesting potential deficits in emotional processing during face perception.

BACKGROUND:Exercise interventions play a key role in disease prevention and treatment,which can effectively activate the nuclear factor erythroid2-related factor 2(Nrf2)signaling pathway to prevent the occurrence and development of insulin resistance.However,the potential mechanism of Nrf2-targeting exercise therapy strategies in alleviating insulin resistance remains unclear.OBJECTIVE:Based on the relationship between Nrf2,insulin resistance and exercise,to analyze the mechanism and influence of different exercise modes on the activation of Nrf2,thereby elucidating the potential mechanism of Nrf2-targeting exercise therapy strategies in the process of alleviating insulin resistance.METHODS:"Diabetes mellitus,insulin,insulin resistance,nuclear factor E2 related factor 2,oxidative stress,ferroptosis,autophagy,inflammatory response,exercise"were used as search terms in Chinese and English.WanFang Database,CNKI,Google Scholar and PubMed database were searched for relevant literature from inception to October 2024,and a total of 127 core related articles were obtained according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Keap1/Nrf2 signaling pathway,as an important endogenous antioxidant stress pathway,plays an important role in insulin resistance.Activation of Keap1/Nrf2 signaling pathway can enhance the antioxidant capacity of cells,reduce oxidative stress and inflammation,improve insulin signaling,and thus protect insulin resistance.(2)A variety of exercise methods(including aerobic exercise,resistance exercise and high-intensity intermittent exercise)can effectively activate Nrf2 signal,improve the activity of antioxidant kinase and enhance the antioxidant capacity of cells,so as to alleviate oxidative stress damage to a certain extent.(3)By activating Nrf2 signaling pathway,exercise can up-regulate the activity of antioxidant enzymes such as Heme oxygenase 1,superoxide dismutase,catalase,glutathione peroxidase,glutathione,and enhance the antioxidant capacity of cells.In addition,it can also regulate the key enzymes and proteins in the ferroptosis pathway,such as glutathione peroxidase 4,membrane iron transport protein 1,and ferritin heavy chain 1,inhibit the ferroptosis pathway and promote the balance of iron metabolism.In autophagy,the expression of autophagy related genes p62 and ATG5/7 can be enhanced,and the level of microtubule-associated protein 1 light chain 3 is increased,thus regulating autophagy process.At the same time,the activity of tumor necrosis factor-α,nuclear factor-κB,interleukin-6,interleukin-1β and other pro-inflammatory cytokines is decreased,and the inflammatory response can be effectively inhibited.These combined effects can reduce oxidative stress damage,increase insulin sensitivity and improve insulin signaling,and thus have a positive effect on improving insulin resistance.(4)Given that the Keap1/Nrf2 signaling pathway plays an important role in the pathogenesis and treatment of insulin resistance,exercise therapy strategies targeting the Keap1/Nrf2 signaling pathway will help promote the development of"exercise+drug"precision medicine for insulin resistance.

BACKGROUND:Exercise interventions play a key role in disease prevention and treatment,which can effectively activate the nuclear factor erythroid2-related factor 2(Nrf2)signaling pathway to prevent the occurrence and development of insulin resistance.However,the potential mechanism of Nrf2-targeting exercise therapy strategies in alleviating insulin resistance remains unclear.OBJECTIVE:Based on the relationship between Nrf2,insulin resistance and exercise,to analyze the mechanism and influence of different exercise modes on the activation of Nrf2,thereby elucidating the potential mechanism of Nrf2-targeting exercise therapy strategies in the process of alleviating insulin resistance.METHODS:"Diabetes mellitus,insulin,insulin resistance,nuclear factor E2 related factor 2,oxidative stress,ferroptosis,autophagy,inflammatory response,exercise"were used as search terms in Chinese and English.WanFang Database,CNKI,Google Scholar and PubMed database were searched for relevant literature from inception to October 2024,and a total of 127 core related articles were obtained according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Keap1/Nrf2 signaling pathway,as an important endogenous antioxidant stress pathway,plays an important role in insulin resistance.Activation of Keap1/Nrf2 signaling pathway can enhance the antioxidant capacity of cells,reduce oxidative stress and inflammation,improve insulin signaling,and thus protect insulin resistance.(2)A variety of exercise methods(including aerobic exercise,resistance exercise and high-intensity intermittent exercise)can effectively activate Nrf2 signal,improve the activity of antioxidant kinase and enhance the antioxidant capacity of cells,so as to alleviate oxidative stress damage to a certain extent.(3)By activating Nrf2 signaling pathway,exercise can up-regulate the activity of antioxidant enzymes such as Heme oxygenase 1,superoxide dismutase,catalase,glutathione peroxidase,glutathione,and enhance the antioxidant capacity of cells.In addition,it can also regulate the key enzymes and proteins in the ferroptosis pathway,such as glutathione peroxidase 4,membrane iron transport protein 1,and ferritin heavy chain 1,inhibit the ferroptosis pathway and promote the balance of iron metabolism.In autophagy,the expression of autophagy related genes p62 and ATG5/7 can be enhanced,and the level of microtubule-associated protein 1 light chain 3 is increased,thus regulating autophagy process.At the same time,the activity of tumor necrosis factor-α,nuclear factor-κB,interleukin-6,interleukin-1β and other pro-inflammatory cytokines is decreased,and the inflammatory response can be effectively inhibited.These combined effects can reduce oxidative stress damage,increase insulin sensitivity and improve insulin signaling,and thus have a positive effect on improving insulin resistance.(4)Given that the Keap1/Nrf2 signaling pathway plays an important role in the pathogenesis and treatment of insulin resistance,exercise therapy strategies targeting the Keap1/Nrf2 signaling pathway will help promote the development of"exercise+drug"precision medicine for insulin resistance.

Objective:To explore the path way of self-acceptance and implicit attitude on perceived stress and body image disorder among patients with thyroid associated ophthalmopathy, and provide a basis for clinical medical staff to develop intervention measures to reduce patients′ body image impairment.Methods:A cross-sectional survey was conducted using convenience sampling from October 2018 to October 2023 on patients with thyroid associated ophthalmopathy who visited the Huazhong University of Science and Technology Tongji Medical College Affiliated Union Hospital. The survey included the General Information Questionnaire, Perceived Stress Scale, Self-Acceptance Questionnaire, Implicit Association Test, and Body Image Scale.Results:Finally, 310 questionnaires were distributed in total, 303 valid questionnaires were recovered, with an effective recovery rate of 97.7%. Among the 303 patients, there were 87 males and 216 females, aged 25-78 (44.07 ± 4.76) years. The scores for body image impairment, perceived stress, self-acceptance, and implicit attitude in patients with thyroid associated ophthalmopathy were (16.51 ± 4.19), (38.36 ± 6.74), (33.49 ± 10.07), and (0.45 ± 0.11) points, respectively; there was a perceived stress positively correlated with body image disorder and implicit attitude ( r=0.829, 0.636, both P<0.05), perceived stress also negative correlated with self-acceptance ( r=-0.807, P<0.05). The mediating model showed that perceived stress not only had a significant direct effect on body image disorder ( β=0.409, P<0.05), but also indirectly affected body image disorder through three paths, including the independent mediating effect of self-acceptance ( β=0.125, P<0.05), and implicit attitude ( β=0.195, P<0.05), as well as the chain mediating effect of self-acceptance and implicit attitude ( β=0.022, P<0.05), which accounting for 45.5% of the total effect. Conclusions:Self-acceptance and implicit attitude play mediating role in the relationship between perceived stress and body image disorder in patients with thyroid associated ophthalmopathy, medical staff can promote self-acceptance by enhance self-compassion, correct negative implicit attitude, decrease the effect of perceived stress on body image disorder in patients with thyroid associated ophthalmopathy.

Objective:To explore the impact of adverse childhood experiences on psychosomatic symptoms and job burnout in the nursing population.Methods:Utilizing a multistage stratified cluster random sampling meth-od,1 661 nurses were selected.Through a 1∶2 propensity score matching approach,demographic and work-related characteristics were balanced between the positive and negative groups of adverse childhood experiences.Finally,880 cases were successfully matched(positive group:300 cases,negative group:580 cases).Linear regression was employed to explore the relationship between nurses'adverse childhood experiences and psychosomatic symptoms(anxiety,depression,physical symptoms),as well as job burnout.The average treatment effect among the treated(ATT)was calculated.Results:Linear regression results revealed a significant positive association between adverse childhood experiences and scores for anxiety symptoms,depression symptoms,physical symptoms,and job burnout(B=1.68,2.67,2.89,5.90;ATT=1.64,2.58,2.82,5.96,Ps＜0.001).However,there was no statistically signif-icant association with scores for a sense of inadequacy in individual achievements(P＞0.05).Conclusion:Nurses who have experienced childhood adverse experiences may exhibit more severe psychosomatic symptoms and job burnout compared to those who have not experienced such adversities during childhood.

Objective:To analyze the association between osteoporosis and the risk for Alzheimer's disease (AD).Methods:A total of 471 922 study subjects were selected from the UK Biobank database, including 12 818 osteoporosis cases and 459 104 controls. Cox proportional hazard regression model and competing risk model were used to evaluate the association between osteoporosis and AD after adjusting confounding factors. Furthermore, a Mendelian randomization (MR) study was conducted by using the data of two published genome-wide association studies, and 1 050 highly relevant single nucleotide polymorphisms were identified from the bone mineral density data as instrumental variables. The association between bone mineral density and the risk for AD was evaluated by using inverse variance weighted method, MR-Egger regression, and weighted median estimator method. Additionally, sensitivity analyses were performed.Results:After adjusting for confounders, no significant association between osteoporosis and an increased risk for AD was found in the cohort study (Cox proportional hazard regression model analysis: HR=1.10, 95% CI: 0.78-1.56, P=0.588). The MR analysis revealed no association between bone mineral density and the risk for AD (inverse-variance weighted: OR=1.03, 95% CI: 0.98-1.09, P=0.252), and the results remained robust in multiple sensitivity analyses. Conclusion:The study result does not support the association between osteoporosis and risk for AD.

Objective To develop a hypoxia endurance testing system for aviation physiological training of pilots.Methods The hypoxia endurance testing system comprised a low-oxygen mixed gas generator,a pressurization system for low-oxygen mixed gas and a personal breathing apparatus.The low-oxygen mixed gas generator consisted of a main unit composed of an air compressor,a filter,a buffer tank,polymer membrane,a control module,sensors and regulators,wire cables,supporting hoses,etc.;the pressurization system for low-oxygen mixed gas was made up of a protective box,a cooling fan,a motor and a driver,a control module,a solenoid valve,a convergence block,a pressure gauge,etc.;the personal breating apparatus was composed of a gas cylinder,a pressure reducer,an oxygen supply regulator,etc.Forty-eight subjects were selected for hypoxia exposure tests to verify the effectiveness of the system.Results The system developed had the functions of low-oxygen gas preparation,pressurized filling and hypoxia experiment,and the experimental results indicated the acute hypoxia exposure by the system significantly caused signs and symptoms of hypoxia and weakened physiological functions.Conclusion The system developed gains advantages in high accuracy of gas volume fraction control,safety and remarkable effect of simulated hypoxia,and can be an effective tool for acute high-altitude hypoxia testing and training of pilots.[Chinese Medical Equipment Journal,2025,46(10):23-28]

Objective:To explore the impact of adverse childhood experiences on psychosomatic symptoms and job burnout in the nursing population.Methods:Utilizing a multistage stratified cluster random sampling meth-od,1 661 nurses were selected.Through a 1∶2 propensity score matching approach,demographic and work-related characteristics were balanced between the positive and negative groups of adverse childhood experiences.Finally,880 cases were successfully matched(positive group:300 cases,negative group:580 cases).Linear regression was employed to explore the relationship between nurses'adverse childhood experiences and psychosomatic symptoms(anxiety,depression,physical symptoms),as well as job burnout.The average treatment effect among the treated(ATT)was calculated.Results:Linear regression results revealed a significant positive association between adverse childhood experiences and scores for anxiety symptoms,depression symptoms,physical symptoms,and job burnout(B=1.68,2.67,2.89,5.90;ATT=1.64,2.58,2.82,5.96,Ps＜0.001).However,there was no statistically signif-icant association with scores for a sense of inadequacy in individual achievements(P＞0.05).Conclusion:Nurses who have experienced childhood adverse experiences may exhibit more severe psychosomatic symptoms and job burnout compared to those who have not experienced such adversities during childhood.