This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

Objective:To investigate the relationship between serum soluble interleukin-2 receptor(sCD25)and insulin-like growth factor-Ⅰ(IGF-Ⅰ)and the immunophenotype and therapeutic efficacy of newly diagnosed multiple myeloma(MM)patients.Methods:125 newly diagnosed MM patients(MM group)who received treatment at Tianmen First People's Hospital from January 2023 to June 2024 were selected,and another 70 healthy individuals who underwent physical examinations at our hospital during the same period were selected(control group).The serum sCD25 and IGF-Ⅰ levels in newly diagnosed MM patients of different stages were compared,and newly diagnosed MM patients were divide into remission group(76 cases)and non remission group(49 cases)based on treatment efficacy,the serum sCD25 and IGF-Ⅰ levels between the remission group and non remission group were compared.The patients were divided into high sCD25 group and low sCD25 group,high IGF-Ⅰ group and low IGF-Ⅰgroup according to the median levels of serum sCD25 and IGF-Ⅰ,the immunophenotypic differences between high sCD25 group and low sCD25 group,as well as high IGF-Ⅰ group and low IGF-Ⅰ group were analyzed.Serum sCD25 and IGF-Ⅰ for evaluating the efficacy of newly diagnosed MM patients were analyzed by receiver operating characteristic(ROC)curve.Factors affecting the therapeutic effect of newly diagnosed MM patients were analyzed by multivariate logistic regression analysis.Results:Serum sCD25 and IGF-Ⅰ levels in the control group were significantly lower than those in the MM group(P＜0.05).There was a statistically significant difference in serum sCD25 and IGF-Ⅰ levels among newly diagnosed MM patients at different stages(P＜0.05).Serum sCD25 and IGF-Ⅰ levels in stage Ⅲ newly diagnosed MM patients were significantly higher than those in stage Ⅰ and Ⅱ(P＜0.05),And stage Ⅱ was higher than that in stage Ⅰ(P＜0.05).The positive expression rate of CD56 in the high sCD25 group was higher than that in the low sCD25 group,there was no significant difference in the positive expression rates of CD117 and CD200 between the two groups(P＞0.05).The positive expression rates of CD56 and CD117 in the high IGF-Ⅰ group were higher than those in the low IGF-Ⅰ group(P＜0.05),and there was no significant difference in the positive expression rate of CD200 between the two groups(P＞0.05).Serum sCD25 and IGF-Ⅰ levels in the remission group were significantly lower than those in the non remission group(P＜0.05).ROC curve analysis showed that,the area under the curve(AUC)for evaluating the efficacy of newly diagnosed MM patients using serum sCD25 and IGF-Ⅰ detection alone and in combination were 0.748,0.775 and 0.832,respectively,and the AUC for combined detection was greater than that for each indicator detected separately.The results of multivariate Logistic regression model showed that elevated serum sCD25 level,elevated serum IGF-Ⅰ level and MM stage Ⅲ were independent risk factors affecting the efficacy of newly diagnosed MM patients(P＜0.05).Conclusion:Serum sCD25 and IGF-Ⅰ levels are closely related to the disease stage and therapeutic efficacy of newly diagnosed MM patients.Combined detection has a high evaluation value for efficacy and can be used as an important evaluation index affecting efficacy.

This consensus focuses on the transcatheter left atrial appendage closure(LAAC).In response to the growing number of patients with atrial fibrillation,advancements in LA AC technology,and evolving clinical needs,it has been updated by the Structural Heart Disease Professional Committee of the Cardiovascular Physicians Branch of the Chinese Medical Doctor Association.The incidence of atrial fibrillation is increasing with population aging,leading to elevated stroke risk.LAAC offers an effective preventive solution.The consensus provides a detailed overview of LAAC's developmental trajectory,including its pivotal role in the comprehensive management of atrial fibrillation,milestone events in China,and substantial evidence-based data.Regarding team composition,the consensus outlines the inclusion of multidisciplinary professionals with clearly defined roles.It precisely delineates indications as non-valvular atrial fibrillation patients with high stroke risk and qualifying scores in specific scenarios,while also listing contraindications.Methodological aspects are comprehensively addressed,encompassing imaging assessments(such as the roles and key considerations of TTE,TEE,and cardiac CTA),the operational protocols for various devices(the selection,implantation,evaluation,and adjustment for plug-and disc-type devices),and perioperative management.Potential perioperative complications,such as pericardial effusion,stroke,and device dislocation,are reviewed with analyses of their causes and corresponding management strategies.Postoperative antithrombotic treatment strategies are tailored to different stages(intensive,consolidation,and special cases),while detailed follow-up plans(timelines,methods,content,and outcome assessment)are provided.The consensus also explores surgical approach options,highlighting the features and applications of"one-stop"and simplified LAAC procedures.Looking ahead,it focuses on the expansion of the applicable population,technological improvements,device innovations,further advancement of combined treatment,and optimized medication strategies.This comprehensive,precise,and forward-looking guidance aims to enhance LAAC's clinical practice and development,fostering its standardization,precision,and continuous innovation.

This consensus focuses on the transcatheter left atrial appendage closure(LAAC).In response to the growing number of patients with atrial fibrillation,advancements in LA AC technology,and evolving clinical needs,it has been updated by the Structural Heart Disease Professional Committee of the Cardiovascular Physicians Branch of the Chinese Medical Doctor Association.The incidence of atrial fibrillation is increasing with population aging,leading to elevated stroke risk.LAAC offers an effective preventive solution.The consensus provides a detailed overview of LAAC's developmental trajectory,including its pivotal role in the comprehensive management of atrial fibrillation,milestone events in China,and substantial evidence-based data.Regarding team composition,the consensus outlines the inclusion of multidisciplinary professionals with clearly defined roles.It precisely delineates indications as non-valvular atrial fibrillation patients with high stroke risk and qualifying scores in specific scenarios,while also listing contraindications.Methodological aspects are comprehensively addressed,encompassing imaging assessments(such as the roles and key considerations of TTE,TEE,and cardiac CTA),the operational protocols for various devices(the selection,implantation,evaluation,and adjustment for plug-and disc-type devices),and perioperative management.Potential perioperative complications,such as pericardial effusion,stroke,and device dislocation,are reviewed with analyses of their causes and corresponding management strategies.Postoperative antithrombotic treatment strategies are tailored to different stages(intensive,consolidation,and special cases),while detailed follow-up plans(timelines,methods,content,and outcome assessment)are provided.The consensus also explores surgical approach options,highlighting the features and applications of"one-stop"and simplified LAAC procedures.Looking ahead,it focuses on the expansion of the applicable population,technological improvements,device innovations,further advancement of combined treatment,and optimized medication strategies.This comprehensive,precise,and forward-looking guidance aims to enhance LAAC's clinical practice and development,fostering its standardization,precision,and continuous innovation.

With the aging of the population,the disease burden of heart valve disease in China has significantly increased.In recent years,the interventional treatment for heart valve disease has flourished,among which transcatheter aortic valve replacement(TAVR)has become the first-line treatment for elderly patients with aortic valve stenosis.China started relatively late in the field of interventional treatment for heart valve disease.The construction of heart valve centers helps to standardize the diagnosis and interventional treatment of heart valve disease in China and improve the management of prognosis for patients.Up to December 2024,a total of 453 centers have participated in the construction of heart valve centers,including 100 construction centers and 40 certification centers.The National Transcatheter Valve Therapeutics Registry(NTCVR)database has reported a total of 28 594 cases,with approximately 50％of Chinese TAVR cases recorded in NTCVR database.The construction of the heart valve centers has shown initial results,significantly optimizing the process of diagnosis and treatment of heart valve disease and improving the prognosis.At present,there are still many shortcomings in the construction of heart valve centers.For example,the follow-up rate of patients after discharge is low,and long-term management after discharge needs to be further improved.There is still a gap in some indicators between construction centers and certification centers,and the promotion of high-quality management of interventional treatment of heart valve disease in China is still a long way to go.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Objective:To explore medical students'cognition,current status,and demands regarding practical skills training in a medical college under the background of new medical science.Methods:A cross-sectional survey was conducted among medical undergraduates from Year 1 to Year 5 in a medical college.A self-designed scale was used to investigate the cognition,current status,and demands related to new medical education concepts.Pearson correlation analysis was used to analyze the relationship between satisfaction with practical teaching facilities and variables including understanding of new medical education,curriculum design,and proportion of practical teaching.Multiple linear regression was conducted to investigate the factors influencing satisfaction.Results:Among 1 253 participants,70.71%acquired new medical science information through online media,while 52.99%learned about it via school courses.Over 80%endorsed"whole-cycle health management"(preventive care before disease onset 91.94%,disease treatment 81.72%,and post-illness rehabilitation 82.60%).Experimental courses(85.16%),clinical skills training(66.88%),and social practice(66.24%)were primary practical forms,but the participation rates of research practice(40.78%)and innovation/entrepreneurship practice(34.72%)was comparatively lower.The satisfaction with practical teaching was positively correlated with adequacy of faculty guidance(r=0.707)and curriculum rationality(r=0.522)(P＜0.01).The multiple linear regression analysis showed that faculty guidance(β=0.436)and the proportion of practical teaching(β=0.319)were the key predictors of satisfaction.Conclusion:Medical students'cognition of practical skills training,curriculum optimization,and adequacy of faculty guidance significantly influence satisfaction with practical teaching,with faculty guidance and rationality of practical process playing key roles.