Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective It investigates the current status of negative defensive medical behavior tendencies among medical students and explores influencing factors,aiming to provide evidence for improving medical students' propensity for negative defensive medical practices.Methods In February 2023,a cluster sampling approach was employed to recruit 297 medical students from a medical college-affiliated hospital in Province H.Descriptive statistics,chi-square tests,and correlation analyses were conducted to assess negative defensive medical behavior tendencies.Structural equation modeling(SEM)was utilized to explore multidimensional influencing factors.Results 45％of medical students demonstrated high-level negative defensive medical behavior tendencies.Statistically significant differences were observed between genders(x2=5.569,P＜0.05)and only-child/non-only-child groups(x2=6.104,P＜0.05).Positive correlations were identified between negative defensive medical behaviors and role stress(r=0.217,P＜0.01),negative organizational environment evaluation(r=0.395,P＜0.01),and negative social environment evaluation(r=0.405,P＜0.01).Only-child status was confirmed as an influencing factor(β=-0.123,P=0.036).Negative organizational environment evaluation(β=0.504,P＜0.001)and negative social environment evaluation(β=0.193,P=0.039)showed significant positive effects.Conclusion Immediate interventions-including role-specific risk allocation,organizational ecosystem reconstruction,and social environment governance-require urgent implementation to address early-stage behavioral deviance,counteract the solidification of defensive medical thinking patterns,and reduce predispositions toward negative professional behaviors among medical trainees.

Objective To analyze the influence path of medical students'professional identity on positive defensive medical behaviors and examine the mediating effect of medical risk perception between the two,aiming to provide theoretical support and practical reference for medical education to actively adapt to the demands of the medical and health system reform and promote the scientific guidance of positive defensive medical behaviors.Methods ln 2020,a questionnaire survey was conducted among medical students from four medical colleges in Heilongjiang Province using cluster sampling method,and data analysis was performed using SPSS 27.0 software.Results Medical students'professional identity showed a significant positive correlation with their positive defensive medical behavior(β=0.225,P＜0.001),with medical risk perception acting as a partial mediator(indirect effect accounting for 19%of the total effect).Professional identity(β=0.183,P＜0.001)and medical risk perception(β=0.195,P＜0.001)exerted direct positive effects on positive defensive medical behavior.Conclusion Medical students'professional identity drives them to adopt positive defensive medical behaviors by strengthening their sense of responsibility ethics and risk cognition ability,and medical risk perception is a key mediating variable in this process.Educational management should integrate policy-oriented clinical decision-making training and balance medical safety and efficiency through the collaborative mechanism of"professional identity-risk perception-behavioral practice".

Objective To compare the adverse reactions to pegasparaginase(PEG-ASP)and Erwiniaasparaginase(ASP)in the treat-ment of pediatric acute lymphoblastic leukemia(ALL)and to provide clinical guidance for treatment.Methods A total of 13 patients who were switched from PEG-ASP to Erwinia ASP due to allergic reactions during the induction phase of ALL treatment at the Depart-ment of Hematology and Oncology,Children's Hospital Affiliated of Zhengzhou University between February 2022 and February 2023 were selected as the case group.A control group of 26 patients treated with PEG-ASP and matched for sex at a ratio of 1∶2 was also selected.Pre-and post-treatment coagulation function,blood biochemistry,blood ammonia level,and gastrointestinal reactions were compared between the groups.Results There were no significant differences in AST,TB,UB,TC,TG,AMY,UN,Cr,APTT,and Fbg levels between the two groups,pre-and post-treatment.However,ALT,GGT,BB,and Glu levels were higher in the control group,whereas albumin was lower than in the case group(P<0.05).Both groups had an increased post-treatment blood ammonia level(P<0.05),with significantly a higher level observed in the case group than in the control group(P<0.001).No significant differences in adverse gastro-intestinal reactions were observed between the two groups.Conclusion Erwinia ASP and PEG-ASP affected liver function in pediatric ALL re-induction therapy with minimal effects on coagulation and weaker gastrointestinal reaction.Erwinia ASP significantly affected the blood ammonia level,and both treatments caused mild gastrointestinal reactions.Regular blood ammonia monitoring,post Erwinia ASP treatment,is recommended.

Objective It investigates the current status of negative defensive medical behavior tendencies among medical students and explores influencing factors,aiming to provide evidence for improving medical students' propensity for negative defensive medical practices.Methods In February 2023,a cluster sampling approach was employed to recruit 297 medical students from a medical college-affiliated hospital in Province H.Descriptive statistics,chi-square tests,and correlation analyses were conducted to assess negative defensive medical behavior tendencies.Structural equation modeling(SEM)was utilized to explore multidimensional influencing factors.Results 45％of medical students demonstrated high-level negative defensive medical behavior tendencies.Statistically significant differences were observed between genders(x2=5.569,P＜0.05)and only-child/non-only-child groups(x2=6.104,P＜0.05).Positive correlations were identified between negative defensive medical behaviors and role stress(r=0.217,P＜0.01),negative organizational environment evaluation(r=0.395,P＜0.01),and negative social environment evaluation(r=0.405,P＜0.01).Only-child status was confirmed as an influencing factor(β=-0.123,P=0.036).Negative organizational environment evaluation(β=0.504,P＜0.001)and negative social environment evaluation(β=0.193,P=0.039)showed significant positive effects.Conclusion Immediate interventions-including role-specific risk allocation,organizational ecosystem reconstruction,and social environment governance-require urgent implementation to address early-stage behavioral deviance,counteract the solidification of defensive medical thinking patterns,and reduce predispositions toward negative professional behaviors among medical trainees.

Solid-phase extraction(SPE)combined with surface-enhanced Raman spectroscopy(SERS)has emerged as a promising analytical technique for detection and analysis of trace components in complex sample matrices.SPE enriches analytes through selective adsorption and solvent elution,effectively increasing the concentration and signal intensity.SERS enables ultra-sensitive and highly selective molecular analysis through the use of SERS-active substrates engineered to amplify Raman signals.The integration of these two techniques overcomes the limitations of conventional Raman spectroscopy in low-concentration detection field,while significantly improving sample preparation efficiency and analytical accuracy.This review provided a comprehensive overview of the characteristics of three SPE-SERS coupling modes,including two-step,one-step,and online integration.Special emphasis was placed on recent advancements in one-step SPE-SERS approaches based on novel functional adsorbent materials such as graphene,metal-organic frameworks,covalent organic frameworks,and molecularly imprinted polymers.Furthermore,future directions and development prospects of SPE-SERS technology were discussed.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective:To explore a new surgical approach [anteromedial approach of the hip (AMA)] for Pipkin Ⅰ and Ⅱ femoral head fractures through an imaging and anatomical study.Methods:The hip imaging data were collected of the 38 patients who had undergone lower limb CT angiography for open tibiofibular fractures at Department of Orthopaedics, The Sixth People’s Hospital, School of Medicine, Shanghai Jiao Tong University from June 2023 to January 2024. There were 20 males aged (40.9±3.5) years and 18 females aged (41.5±3.3) years. The origins and shapes of the femoral artery and its main branches were observed. The distances between the femoral head and the femoral artery, the medial femoral circumflex artery, and the lateral femoral circumflex artery were measured. Four fresh adult cadavers were collected, including 2 males and 2 females. Their ages of death were 56, 65, 72 and 78 years old, respectively. An incision was made along the axis of the limb at the midpoint of the inguinal ligament at the 4 fresh cadavers. After the femoral head was exposed through the gap between the femoral artery and the femoral nerve, the range of the femoral head exposed was marked.Results:The femoral artery ran along the anteromedial side of the femoral head. The shortest distance between the medial femoral circumflex artery and the femoral head was (13.1±5.7) mm, and the shortest distance between the origin of the lateral femoral circumflex artery and the femoral head (21.6±8.6) mm. On the lateral view of CT angiography, the distance between the femoral artery and the femoral head was (20.6±4.9) mm at the level of the apex of greater trochanter. Gross observation on the cadavers found only small branches of vessels between the femoral artery and the femoral nerve. After the femoral artery and femoral nerve were respectively pulled medially and laterally, the anterior-inferior part of the femoral head was exposed directly by pulling the muscles to open the joint capsule. The exposure range of the femoral head was further expanded through internal and external rotation of the hip joint under traction. The anatomical gap between the femoral artery and the femoral nerve was named the AMA.Conclusion:AMA utilizes the potential gap between the femoral artery and the femoral nerve, providing a new surgical approach for exposure and fixation of Pipkin type Ⅰ and Ⅱ femoral head fractures.

Objective To compare the adverse reactions to pegasparaginase(PEG-ASP)and Erwiniaasparaginase(ASP)in the treat-ment of pediatric acute lymphoblastic leukemia(ALL)and to provide clinical guidance for treatment.Methods A total of 13 patients who were switched from PEG-ASP to Erwinia ASP due to allergic reactions during the induction phase of ALL treatment at the Depart-ment of Hematology and Oncology,Children's Hospital Affiliated of Zhengzhou University between February 2022 and February 2023 were selected as the case group.A control group of 26 patients treated with PEG-ASP and matched for sex at a ratio of 1∶2 was also selected.Pre-and post-treatment coagulation function,blood biochemistry,blood ammonia level,and gastrointestinal reactions were compared between the groups.Results There were no significant differences in AST,TB,UB,TC,TG,AMY,UN,Cr,APTT,and Fbg levels between the two groups,pre-and post-treatment.However,ALT,GGT,BB,and Glu levels were higher in the control group,whereas albumin was lower than in the case group(P<0.05).Both groups had an increased post-treatment blood ammonia level(P<0.05),with significantly a higher level observed in the case group than in the control group(P<0.001).No significant differences in adverse gastro-intestinal reactions were observed between the two groups.Conclusion Erwinia ASP and PEG-ASP affected liver function in pediatric ALL re-induction therapy with minimal effects on coagulation and weaker gastrointestinal reaction.Erwinia ASP significantly affected the blood ammonia level,and both treatments caused mild gastrointestinal reactions.Regular blood ammonia monitoring,post Erwinia ASP treatment,is recommended.

Objective To analyze the influence path of medical students'professional identity on positive defensive medical behaviors and examine the mediating effect of medical risk perception between the two,aiming to provide theoretical support and practical reference for medical education to actively adapt to the demands of the medical and health system reform and promote the scientific guidance of positive defensive medical behaviors.Methods ln 2020,a questionnaire survey was conducted among medical students from four medical colleges in Heilongjiang Province using cluster sampling method,and data analysis was performed using SPSS 27.0 software.Results Medical students'professional identity showed a significant positive correlation with their positive defensive medical behavior(β=0.225,P＜0.001),with medical risk perception acting as a partial mediator(indirect effect accounting for 19%of the total effect).Professional identity(β=0.183,P＜0.001)and medical risk perception(β=0.195,P＜0.001)exerted direct positive effects on positive defensive medical behavior.Conclusion Medical students'professional identity drives them to adopt positive defensive medical behaviors by strengthening their sense of responsibility ethics and risk cognition ability,and medical risk perception is a key mediating variable in this process.Educational management should integrate policy-oriented clinical decision-making training and balance medical safety and efficiency through the collaborative mechanism of"professional identity-risk perception-behavioral practice".