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.

Cardiovascular disease(CVD)is the leading cause of death among patients with non-alcoholic fatty liver disease(NAFLD),which is also recognized as an independent risk factor for CVD.Exercise has emerged as a prom-ising therapeutic approach that can ameliorate a range of conditions,including those related to the cardiovascular and en-docrine systems.Recent research has highlighted the critical role of the integrated stress response(ISR)in the mecha-nisms and manifestations of these diseases.Notably,exercise influences ISR protein markers,regulates protein expres-sion,alleviates stress levels,and ultimately impacts disease onset and progression.Current studies suggest that the effects of ISR modulation through various exercise conditions differ for the heart and liver.However,evidence indicates that un-der specific circumstances,exercise can engage the PERK and GCN2 pathways to inhibit the ISR,thereby regulating glu-cose and lipid metabolism,apoptosis,and endoplasmic reticulum stress.These actions contribute to the protection of car-diac and hepatic function,ultimately improving outcomes in CVD and NAFLD.This review aims to provide novel insights and a theoretical foundation for the role of exercise in mitigating the onset of NAFLD,CVD,and related disorders.

Cardiovascular disease(CVD)is the leading cause of death among patients with non-alcoholic fatty liver disease(NAFLD),which is also recognized as an independent risk factor for CVD.Exercise has emerged as a prom-ising therapeutic approach that can ameliorate a range of conditions,including those related to the cardiovascular and en-docrine systems.Recent research has highlighted the critical role of the integrated stress response(ISR)in the mecha-nisms and manifestations of these diseases.Notably,exercise influences ISR protein markers,regulates protein expres-sion,alleviates stress levels,and ultimately impacts disease onset and progression.Current studies suggest that the effects of ISR modulation through various exercise conditions differ for the heart and liver.However,evidence indicates that un-der specific circumstances,exercise can engage the PERK and GCN2 pathways to inhibit the ISR,thereby regulating glu-cose and lipid metabolism,apoptosis,and endoplasmic reticulum stress.These actions contribute to the protection of car-diac and hepatic function,ultimately improving outcomes in CVD and NAFLD.This review aims to provide novel insights and a theoretical foundation for the role of exercise in mitigating the onset of NAFLD,CVD,and related disorders.

Objective:The aim is to construct an evaluation framework for clinical research benefits,and provide a reference for the formulate of evaluation standards for clinical research benefits.Methods:The Delphi method was used to carry out expert consultation,and the mean,score of importance,coefficient of variation and coordination,etc.of evaluation indicators were summarized and calculated,to screen evaluation indicators for clinical research benefits.Results:Twenty-three experts in this field were selected for correspondence,and their enthusiasm was 100%in both rounds,the authority coefficients were≥0.90,and Kendall's coefficients of concordance were<0.25(P<0.001).By referring to the mean and coefficient of variation of the indicators,as well as combining them with expert suggestions,an evaluation framework for clinical research benefits was ultimately formed with 2 primary indicators,5 secondary indicators,and 8 tertiary indicators.Conclusion:The evaluation framework for clinical research benefits constructed in this paper can comprehensively evaluate the research benefits,as well as provide a basis for reasonably determining the research risk-benefit ratio and developing quantitative evaluation tools for clinical research benefits.

With the rapid development and widespread application of artificial intelligence(AI)technology,it has brought convenience to people's lives and work,while bringing a series of ethical challenges such as lack of transparency,privacy leakage,limited autonomy in decision-making,and blurred responsibility attribution.By comparing the ethical risk governance of the application of AI in the medical field,this paper systematically analyzed 30 policy regulations issued by 10 countries and international organizations,revealing the consensus and differences in ethical governance of medical AI internationally.The results showed that transparency,fairness and justice,non-harm,privacy protection,freedom and autonomy,responsibility,and people-oriented principles were seven internationally recognized ethical principles,providing important guidance for building a safe,trustworthy,and humane-respecting medical AI ecosystem.In addition,this paper deeply compared the risk assessment methods in the guidelines of China,the United States,and the European Union,as well as found differences in risk types,risk grading,and risk assessment process standards.These differences not only reflect diversities in different cultural,legal backgrounds,and regulatory concepts,but also highlight the necessity of strengthening international cooperation in the context of globalization.Therefore,it is recommended to develop ethical risk governance standards and norms for medical AI that applicable to China's national conditions.Based on drawing on international experience,proactively carry out risk assessments,reduce ethical challenges,and promote the healthy and rational application of medical AI technology.

The aim of this study was to investigate the effects of high-intensity interval training(HIIT)on lipopolysaccharide(LPS)-induced septic myocardial injury in mice and the roles of NLRP3 inflammasome and macrophage M1 polarization in the process.C57BL/6 male mice were randomly divided into 4 groups:control(CON)group,LPS(L)group,HIIT+saline injection(E)group,and HIIT+LPS(EL)group.Six weeks of HIIT intervention was followed by intraperitoneal injection of LPS,and cardiac function indexes were measured by echocardiography 12 hours post the injection.Hematoxylin-eosin(HE)staining was used to evaluate the morphology and pathological characteristics of myocardium for assessing myocardial damage score;enzyme-linked immunosorbent assay(ELISA)was used to test the content of myocardial damage indicators(AST,CK-MB,LDH);RT-PCR was used to detect the relative mRNA levels of NLRP3 inflammasome(NLRP3,Caspase-1),atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),myeloperoxidase(MPO)and macrophage M1-associated inflammasome factors(IL-1β,TNF-α,IL-6);Western blot was applied to measure the protein expression of inducible nitric oxide synthase(iNOS)and apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)in cardiac tissues;immunofluorescence staining was used to detect the protein expression of NLRP3 inflammasome,ASC,IL-18 and iNOS.Compared with the CON group,mice in the LPS group showed obvious decrease in body weight,a significant decrease in EF and FS,a significant increase in LVESD and LVEDD,obvious pathological damage in myocardial tissue,a significant increase in myocardial damage fraction,a significant increase in serum myocardial damage indexes,and a significant increase in the expression levels of BNP,MPO,NLRP3 inflammasome,iNOS,IL-1β,IL-6 and TNF-α.HIIT treatment could reverse these changes mentioned above in model mice.In conclusion,6 weeks of HIIT inhibits the activation of LPS-induced NLRP3 inflammasome and suppressed macrophage M1-type polarization,thereby combating septic myocardial injury.

The prevention and treatment of cardiovascular diseases have always been a focus of attention in re-lated fields.This paper discusses the application and mechanism of exogenous and endogenous supplementation with β-hy-droxybutyrate in the prevention and treatment of cardiovascular diseases such as myocardial ischemia,myocardial infarc-tion,diabetic cardiomyopathy,hypertension,myocardial inflammation,hypertrophic cardiomyopathy and heart failure.Exogenous β-hydroxybutyrate supplementation can quickly and directly provide substitute energy for the heart and thus prevent and treat heart injury.The comprehensive effect of exogenous β-hydroxybutyrate supplementation is significantly better than that of endogenous β-hydroxybutyrate.Endogenous fatty acid,obtained through a ketogenic diet,needs to be oxidized to β-hydroxybutyrate in vivo for energy supply,which is greatly influenced by glucose and lipid metabolism under the conditions of the basic disease itself.At present,ketogenic diet is not recommended for use in the prevention and treat-ment of myocardial ischemia or myocardial infarction,and in the treatment of diabetic cardiomyopathy or hypertension.

Objective To investigate the expression of serum long non-coding RNA MEG3 and microRNA(miR)-195-5p in patients with severe necrotizing pancreatitis and their relationship with the severity and prognosis of severe necrotizing pancreatitis.Methods A total of 122 patients with acute pancreatitis admitted to Cangzhou Central Hospital from October 2020 to January 2023 were selected as the research objects.Ac-cording to the severity of the disease,the patients were divided into severe necrotizing pancreatitis(severe group,53 cases)and non-severe necrotizing pancreatitis(non-severe group,69 cases).According to the prog-nosis of alternate ending with severe necrotizing pancreatitis can be divided into good prognosis group(38 ca-ses)and poor prognosis group(15 cases).At the same time,50 healthy people who underwent physical exami-nation in the hospital during the same period were selected as the control group.The clinical data and serum levels of lncRNA MEG3 and miR-195-5p in each group were compared.Spearman correlation analysis was used to analyze the relationship between serum levels of lncRNA MEG3,miR-195-5p and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)and Ranson scores.Multivariate Logistic regression was used to analyze the influencing factors of poor prognosis in patients with severe necrotizing pancreatitis.The receiver operating characteristic(ROC)curve was used to analyze the value of lncRNA MEG3 and miR-195-5p in eval-uating the prognosis of patients with severe necrotizing pancreatitis.Results There was no significant differ-ence in age,gender,body mass index,underlying disease and etiology between severe group and non-severe group(P>0.05).Compared with the non-severe group,APACHEⅡ and Ranson scores were significantly in-creased in the severe group(P<0.05).Compared with the control group,the serum levels of lncRNA MEG3 and miR-195-5p in the non-severe group and the severe group were decreased(P<0.05),and the serum levels of lncRNA MEG3 and miR-195-5p in the severe group were lower than those in the non-severe group(P<0.05).Spearman correlation analysis showed that serum levels of lncRNA MEG3 and miR-195-5p in AP pa-tients were negatively correlated with APACHEⅡ and Ranson scores(P<0.05).Multivariate Logistic re-gression analysis showed that APACHEⅡ and Ranson scores and serum levels of lncRNA MEG3 and miR-195-5p were independent risk factors for poor prognosis in patients with severe necrotizing pancreatitis(P<0.05).ROC curve results showed that the area under the curve(AUC)of lncRNA MEG3 and miR-195-5p for evaluating the poor prognosis of patients with severe necrotizing pancreatitis was 0.767 and 0.777,respectively,the sensitivity was 86.7%and 80.0%,and the specificity was 49.9%and 45.8%,respectively.The AUC of combined e-valuation was 0.982,and the sensitivity and specificity were 86.7%and 78.8%,respectively.Conclusion The serum levels of lncRNA MEG3 and miR-195-5p are related to the severity and prognosis of severe necrotizing pancreatitis,which can evaluate the severity and predict the prognosis of severe necrotizing pancreatitis.

Humans ; Asthma/drug therapy* ; Biological Therapy

【Objective:】 To deeply understand the current situation and hotspots of drug clinical trials risk management in China. 【Methods:】 Co-word analysis and social network analysis were used to sort out the study results of risk management in drug clinical trials in China. 【Results:】 The trend of risk research of drug clinical trials in China was generally on the rise. The research hotspots focused on four areas: drug supervision and pharmacovigilance, risk management of drug clinical trial institutions, ethical review of drug clinical trials, and risk management of drug clinical trials. 【Conclusion:】 In the future, China should gradually improve the risk management system and supervision system of drug clinical trials, explore to establish a risk-based quality management and ethical review system of drug clinical trials, and enhance the risk assessment and coping ability of institutions.