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.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

OBJECTIVE T o explore the long-term effect of multidimensional evidence-based interventions based on i-PARIHS theoretical framework on reduction of incidence of central line-associated bloodstream infections(CLABSI)in pediatric intensive care units(PICU)of pediatrics department and evaluate the impact on nurses'compliance to taking the interventions and use intensity of catheters.METHODS By means of quasi-experimental design,the multidimensional intervention system covering multidisciplinary collaboration,standardized operation procedures,information system optimization and hierarchical training was established and staged for implementa-tion of 5 years(from T0 baseline stage to T3 maintenance stage).The variations in implementation rates of cathe-ter maintenance(daily maintenance,dressings change,catheter removal)were analyzed by Chi-square test,and the change of incidence of CLABSI was monitored with the use of statistical process control U chart.RESULTS The nurses'compliance to operations was remarkably improved(P＜0.05)o The implementation rate of dressings change continuously increased from 52.91％in T0 to81.62％in T3(x2=72.444,P＜0.001),the implementa-tion rate of catheter removal increased from 48.72％to 79.31％(x2=8.179,P=0.042).The incidence rate of CLABSI decreased from 1.92％0 in 2019 to 0.5％0 in 2022,and the control chart showed that most of the months fluctuated within control limits.CONCLUSIONS The multidimensional evidence-based interventions can achieve a long term control of CLABSI by raising the nurses' compliance to operations.The information monitoring and closed-loop management are crucial to maintenance of the interventional effect,and the risk early warning system should be optimized with the combination of artificial intelligence technology.

Objective To investigate the relationship between serum orexin-A(OXA)and aspartate amin-otransferase(AST)levels and the disease severity and prognosis in patients with acute ischemic stroke(AIS).Methods A total of 167 AIS patients(AIS group)treated at Hebei Provincial People's Hospital from January 2021 to January 2024 and 84 healthy individuals undergoing physical examinations(control group)were selected as the research objects.AIS patients were categorized by severity into mild AIS group[National Institutes of Health Stroke Scale(NIHSS)score＜5,42 cases],moderate AIS group(NIHSS score 5—＜16,56 cases),moderate-to-severe AIS group(NIHSS score 16—＜21,36 cases),and severe AIS group(NIHSS score ≥21,33 cases).Based on 3-month prognosis(modified Rankin scale),patients were divided into poor prognosis group(＞2 grade,54 cases)and good prognosis group(≤2 grade,113 cases).Spearman correlation analysis was used to assess the relationship between NIHSS scores and serum OXA and AST levels in AIS pa-tients.Multivariate unconditional Logistic regression was used to determine the relationship between serum OXA and AST levels and the prognosis of AIS patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of serum OXA and AST levels for prognosis.Results Compared with the control group,serum OXA level in the AIS group was lower,while AST level was higher(P＜0.05).Ser-um OXA level progressively decreased,and AST level progressively increased across the mild,moderate,mod-erately severe,and severe AIS groups(P＜0.05).NIHSS score was negatively correlated with serum OXA level and positively correlated with AST level in AIS patients(P＜0.05).High OXA level was an independent protective factor for poor prognosis in AIS patients,while high AST level was an independent risk factor(P＜0.05).The area under the curve(AUC)of the combined assessment of serum OXA and AST levels in predic-ting poor prognosis in AIS patients was 0.873,which was greater than the AUC of OXA(0.793)and AST(0.770)alone(P＜0.05).Conclusion In AIS patients,lower serum OXA level and higher AST level are as-sociated with disease severity and poor prognosis.The combined evaluation of serum OXA and AST levels has higher predictive value for AIS prognosis.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Objective To investigate the correlations of serum levels of platelet activation com-plex-1(PAC-1)and soluble tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)with neu-rological deficit and clinical prognosis in patients with acute cerebral infarction(ACI).Methods A total of 170 ACI patients(ACI group)and 85 healthy volunteers(control group)were enrolled in this study.Based on severity of neurological deficit assessed by the National Institutes of Health Stroke Scale(NIHSS)score,ACI patients were divided into of mild neurological deficit group(43 cases),moderate neurological deficit group(57 cases),moderate-to-severe neurological deficit group(37 cases),and severe neurological deficit group(33 cases).Additionally,based on the 6-month fol-low-up prognosis,ACI patients were divided into 51 cases of poor prognosis group and 119 cases of good prognosis group.Enzyme-linked immunosorbent assay was used to measure serum levels of PAC-1 and sTWEAK.Spearman correlation analysis was performed to evaluate their correlations with NIHSS scores in ACI patients.Multivariate unconditional Logistic regression analysis was conducted to determine their relationships with clinical prognosis.Receiver operating characteristic curves were used to explore their evaluation efficacy for poor clinical prognosis.Results Serum levels of PAC-1 and sTWEAK were significantly higher in the ACI group than in the control group(P＜0.05).Ser-um levels of PAC-1 and sTWEAK increased sequentially in the mild,moderate,moderate-to-severe,and severe neurological deficit groups(P＜0.05).Spearman correlation analysis showed that serum levels of PAC-1 and sTWEAK were positively correlated with NIHSS scores in ACI patients(rs=0.715 and 0.706,respectively;P＜0.001).Multivariate unconditional Logistic regression analysis revealed that older age,higher NIHSS score,larger infarct volume,higher PAC-1 level,and higher sTWEAK level were independent risk factors for poor prognosis in ACI patients(P＜0.05).The ar-ea under the curve for the combined assessment of serum PAC-1 and sTWEAK levels for poor clini-cal prognosis in ACI patients was 0.895,which was greater than the areas under the curve for the individual assessments(0.792 and 0.786,respectively;P＜0.05).Conclusion Elevated serum levels of PAC-1 and sTWEAK are closely related to increased neurological deficit and poor clinical prognosis in ACI patients.The combined detection of these two markers has high evaluation efficacy for clinical prognosis in ACI patients.

Objective:To explore the association between sublingual microcirculatory perfusion vessel proportion (PPV), high mobility group protein B1 (HMGB1), and sepsis-induced coagulopathy (SIC), and to identify early predictive markers for clinical intervention.Methods:A total of 66 septic patients admitted to the Respiratory Intensive Care Unit (RICU) between November 2021 and May 2024 were enrolled. Based on SIC diagnosis within 24 hours of admission, patients were categorized into SIC ( n=36) and non-SIC ( n=30) groups. Clinical parameters, including prothrombin time (PT), activated partial thromboplastin time (APTT), sublingual PPV, and serum HMGB1 levels (measured at 0 h and 6 h), were analyzed. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to identify independent predictors. Results:Compared with the non-SIC group, the SIC group demonstrated significantly prolonged PT ( P<0.05) and APTT ( P<0.05), elevated 0 h lactate levels, and increased 6 h HMGB1. Spearman analysis revealed a positive correlation between 6 h PPV and platelet count ( P<0.05), while an inverse correlation was observed with 6 h PT ( P<0.05). Multivariate regression identified APTT, 6 h PPV, and 6 h HMGB1 as independent predictors of SIC. ROC analysis yielded AUC values of 0.732 for APTT, 0.802 for 6 h PPV, and 0.765 for 6 h HMGB1. The combination of 6 h PPV and HMGB1 further improved predictive accuracy (AUC=0.873). Conclusions:Prolonged APTT, decreased 6 h PPV, and elevated 6h HMGB1 are key indicators of SIC. Integrated assessment of these markers enhances early risk stratification in septic patients, facilitating timely clinical intervention.

Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC50)of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal"dead ends"and"safe bets"for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogen-oxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.