Purpose: Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori. Materials and Methods: A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection. Results: A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively. Conclusions Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.

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 investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis* ; Risk Assessment ; Minerals/chemistry* ; Fossils ; Humans ; Drug Contamination ; Mass Spectrometry

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

Objective To investigate gender differences and age-related changes in body composition(BC)among Miao adults in Rongshui,Guangxi Province,and to provide the basis for assessing nutritional status and health.Methods With informed consent,630 Miao adults(218 males,412 females)were randomly selected for this study.Body composition was assessed using bioelectrical impedance analysis(BIA).Results Weight,fat-free mass,muscle mass,trunk muscle mass,limb muscle mass,waist-to-hip ratio(WHR),body water,presumtion of bone mass and protein were significantly higher in males than in females.And the fat mass,trunk fat mass,limb fat mass,visceral fat content,subcutaneous fat content and percentage of body fat were significantly higher in females than in males.According to the evaluation of body mass index(BMI)and WHR,the proportion of overweight and obesity of Miao adults was higher than the average level of Miao residents,and their obesity was characterized by central obesity.With age,weight,fat mass,muscle mass,fat-free mass,limb muscle mass,limb fat mass,subcutaneous fat content,percentage of body fat,body water,presumtion of bone mass,and protein of Rongshui Miao adults showed a gradual decreasing trend,while visceral fat content and WHR increased progressively.BMI in male Miao adults,along with BMI,fat mass,trunk fat mass,subcutaneous fat content,percentage of body fat,and body water in female Miao adults,showed a trend of increasing followed by decreasing,peaking at the age of 40-49 years.Conclusion The body composition of Miao adults in Rongshui,Guangxi,exhibits significant gender differences and age-related variation change patterns,which may increase the risk of sarcopenia and metabolic diseases with aging.

Objective To investigate the effects of short-term and long-term high-fructose diets on hippocampal neurometabolites and anxiety and depression-like behaviors in mice,revealing the potential mechanisms of high-fructose diets in mood disorders and providing a experimental basis for the prevention and treatment of related diseases.Methods C57BL/6J male mice were randomly divided into two groups,control group(standard diet,n=10)and experimental group(high-fructose diet,n=10).Four weeks(short-term)and eight weeks(long-term)later,each group of mice was examined for body weight and fasting blood glucose,and neurometabolites levels in the hippocampus were detected by hydrogen proton magnetic resonance spectroscopy(1H-MRS),followed by the open-field test,the forced-swimming test,and the tail-suspension test to evaluate anxiety-like and depression-like behaviors.Results High fructose diet for 4 weeks elevated glutamate levels and reduced glutathione and myo-inositol levels in mice,accompanied by shortened immobility time in the forced swim test.High fructose diet for 8 weeks not only led to abnormalities in body weight and glucose metabolism but also caused a reversal decrease in hippocampal glutamate levels and induced significant anxiety-like behaviors,and the decrease in hippocampal glutamate levels showed a significant negative correlation with the enhancement of anxiety-like behaviors.Conclusion Altered hippocampal glutamate levels may be a key contributing factor to the anxiety-like behaviors induced by long-term high-fructose diet.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective To explore the application value of combining the ultrasound breast imaging reporting and data system(BI-RADS)classification with serum fibroblast growth factor receptor 1(FGFR1)and growth differentiation factor 3(GDF3)in the differential diagnosis of benign and malignant breast masses.Methods A total of 159 patients with breast masses were selected and divided into the benign mass group(n=83)and the malignant mass group(n=76)based on postoperative pathological diagnosis.All patients underwent ultrasound examination,and enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of FGFR1 and GDF3.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of ultrasound BI-RADS classification and serum FGFR1 and GDF3 levels for benign and malignant breast masses.Kappa test was applied to analyze the consistency between various diagnostic methods and pathological diagnosis.Results The serum levels of FGFR1 and GDF3,the proportions of irregular morphology,unclear boundaries,spiculation,microcalcifications,blood flow grade Ⅱ-Ⅲ and posterior echo attenuation,RI and PI were higher in the malignant tumor group than those in the benign tumor group(P＜0.05).The area under the curve(AUC)of FGFR1,GDF3 and ultrasound BI-RADS classification in the differential diagnosis of benign and malignant breast masses separately and in combination was 0.802(95%CI:0.732-0.871),0.817(95%CI:0.751-0.884),0.848(95%CI:0.784-0.912)and 0.956(95%CI:0.918-0.993),respectively.The combined diagnosis was more effective than that of the individual diagnosis of each indicator.The consistency between the individual and combined diagnosis of benign and malignant breast masses and pathological diagnosis showed that the Kappa values were 0.517,0.514,0.688 and 0.912,respectively,with the highest consistency observed in the combined diagnosis(P＜0.05).Conclusion Ultrasound BI-RADS classification combined with serum FGFR1 and GDF3 has high application value in the differential diagnosis of benign and malignant breast masses.

Objective:To construct a set of admission evaluation indicators for terminal patients in community hospice wards.Methods:This qualitative study employed a mixed-methods approach. From January to June 2023, 10 physicians working in community hospice wards in Shanghai participated in one-on-one, semi-structured, in-depth interviews. Based on the interview findings and literature review, a preliminary set of admission evaluation indicators was drafted. Subsequently, from July to December 2023, 18 national experts in hospice/palliative care were selected for a two-round Delphi expert consultation to refine the indicators. The final indicator system was established based on the consultation results, and the weight coefficients for each indicator were determined.Results:Sixteen experts completed both rounds of consultation. The experts had a mean age of (52.0±8.3) years and a mean working experience of (14.4±6.8) years. The response rates for the two rounds were 88.9% and 100.0%, respectively. The authority coefficients were 0.875 and 0.894, and the Kendall′s W coordination coefficients were 0.338 (χ2=471.737, P<0.001) and 0.349 (χ2=398.230, P<0.001), respectively. After two rounds of Delphi consultation, a final admission evaluation indicator system was established, comprising 4 first-level indicators and 63 second-level indicators. The first-level indicators and their weight coefficients were: Underlying Disease (0.256 7), Survival Prognosis (0.256 7), Holistic Needs (0.256 6), and Social Environment (0.240 0). Conclusion:The admission evaluation indicator system for terminal patients in community hospice wards developed in this study facilitates the standardized development of community hospice/palliative care services and contributes to providing high-quality care for patients and their families.