As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to pr...As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovas...Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovascular health.This study explores the association between MASLD-related liver fibrosis and cardiac dysfunction,focusing on how liver fibrosis contributes to cardiac remodeling and dysfunction.Cernea et al’s research highlights the strong correlation between liver fibrosis and changes in left ventricular mass,left atrial dimensions,and systolic and diastolic function in diabetic patients.Notably,the study suggests a protective role of sex-hormone binding protein against cardiac remodeling.These findings underline the importance of early detection of liver fibrosis using noninvasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores,which may offer dual protection for both liver and heart health in T2DM patients.Moreover,this study calls for further research into the shared pathogenic mechanisms,including inflammation and fibrosis pathways,between the liver and heart.It advocates for the integration of liver fibrosis screening into cardiovascular risk management,urging clinicians to adopt a more holistic approach in treating patients with MASLD and T2DM.The research has broad implications for preventing cardiovascular complications and improving outcomes in this highrisk population.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is ...BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.展开更多
Objective:To investigate the effect of 12-lead electrocardiogram and 24-hour dynamic electrocardiogram in detecting pacemaker dysfunction and changes in cardiac function indexes in patients with pacemaker implantation...Objective:To investigate the effect of 12-lead electrocardiogram and 24-hour dynamic electrocardiogram in detecting pacemaker dysfunction and changes in cardiac function indexes in patients with pacemaker implantation.Methods:A total of 136 patients with pacemaker implantation in the First Clinical Medical College of Three Gorges University,Institute of Cardiovascular Disease of Three Gorges University and Yicang Central People’s Hospital from January 2023 to December 2024 were selected as the research objects.All patients received 12-lead electrocardiogram and 24-hour holter 3–14 days after implantation.Results:The overall detection rate of various types of pacemaker dysfunction by Holter was significantly higher than that by conventional ECG(27.21%vs.5.15%,χ^(2)=24.402,P<0.001).The overall arrhythmia detection rate of Holter was significantly higher than that of conventional electrocardiogram(57.35%vs.10.29%,χ^(2)=67.277,P<0.001).The time domain indexes of heart rate variability obtained by 24-hour continuous monitoring of Holter were significantly improved compared with those of conventional electrocardiogram(P<0.05).Conclusions:Compared with 12-lead electrocardiogram,24-hour holter monitoring can more accurately detect pacemaker dysfunction and arrhythmia in patients with pacemaker implantation,and provide more comprehensive data of heart rate variability,which is helpful for clinicians to better evaluate the cardiac function of patients and adjust treatment plans.展开更多
BACKGROUND Long-term antipsychotic therapy in psychiatric patients carries significant cardiovascular risks,including QT interval prolongation,myocardial injury,and functional impairment.Guanxinning,a traditional Chin...BACKGROUND Long-term antipsychotic therapy in psychiatric patients carries significant cardiovascular risks,including QT interval prolongation,myocardial injury,and functional impairment.Guanxinning,a traditional Chinese medicine formulation,has demonstrated cardioprotective potential in preclinical studies,but clinical evidence in this population remains limited.AIM To evaluate the cardioprotective effects of Guanxinning against antipsychotic-induced cardiac injury in long-term hospitalized psychiatric patients.METHODS A randomized,double-blind,placebo-controlled trial was conducted with 120 psychiatric inpatients receiving chronic antipsychotic therapy.Participants were allocated to:Intervention group:Conventional antipsychotics+Guanxinning tablets(0.38 g×4 tablets,ter in die);Control group:Conventional antipsychotics+identical placebo;Cardiac assessments at baseline and 12 months included:Electrocardiography(corrected QT interval),echocardiography(left ventricular ejection fraction,left ventricular end-diastolic diameter),serum biomarkers(cardiac troponin I,B-type natriuretic peptide,superoxide dismutase,malondialdehyde,high-sensitivity C-reactive protein).RESULTS Compared to controls,the Guanxinning group showed:Electrophysiological improvement:Corrected QT shortening(438±25 milliseconds vs 465±30 milliseconds,P<0.01).Functional enhancement:Left ventricular ejection fraction increase(58.5%±5.2%vs 53.8%±4.8%,P<0.05),left ventricular end-diastolic diameter reduction(49.8±3.5 mm vs 52.6±3.8 mm,P<0.05),Biochemical modulation:Reduced myocardial injury markers(cardiac troponin I:0.009 ng/mL vs 0.014 ng/mL;B-type natriuretic peptide:52 pg/mL vs 78 pg/mL,P<0.001),improved oxidative stress(superoxide dismutase:↑13.3 U/mL;malondialdehyde:↓0.9 nmol/mL,P<0.001),attenuated inflammation(high-sensitivity C-reactive protein:2.0 mg/L vs 3.2 mg/L,P<0.001).CONCLUSION Guanxinning significantly mitigates antipsychotic-induced cardiac injury in psychiatric patients,demonstrating:Normalization of electrophysiological parameters,Preservation of systolic/diastolic function,suppression of oxidative stress and inflammation.These findings support its clinical application as an adjunctive cardioprotective therapy,potentially through inhibition of myocardial apoptosis and antioxidant upregulation.展开更多
Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyl...Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.展开更多
Human cardiac organoids have revolutionized the study of cardiac development,disease modeling, drug discovery, and regenerative therapies. This review systematically discusses strategies and progress in the constructi...Human cardiac organoids have revolutionized the study of cardiac development,disease modeling, drug discovery, and regenerative therapies. This review systematically discusses strategies and progress in the construction of cardiac organoids, categorizing them into three main types:cardiac spheroids, self-organizing/assembloid organoids, and organoid-on-a-chip systems. This review uniquely integrates the advances in vascularization, organ-on-chip design, and environmental cardiotoxicity modeling within cardiac organoid platforms, offering a critical synthesis that is absent in the literature. In the context of escalating environmental threats to cardiovascular health, there is an urgent need for physiologically relevant models to accurately identify cardiac toxicants and elucidate their underlying mechanisms of action. This review highlights advances in cardiac organoid applications for disease modeling-including congenital heart defects and acquired cardiovascular diseases-drug development, toxicity screening, and the study of environmentally induced cardiovascular pathogenesis. In addition, it critically examines ongoing challenges and underscores opportunities brought by bioengineering approaches. Finally, we propose future directions for developing standardized cardiac organoid platforms with clinical predictability, aiming to expand the utility of this technology across broader research applications.展开更多
Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbl...Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).展开更多
Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male m...Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.展开更多
BACKGROUND:Serum osmolality is a prognostic indicator in critically ill patients.This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest(CA)admitted to...BACKGROUND:Serum osmolality is a prognostic indicator in critically ill patients.This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest(CA)admitted to the intensive care unit(ICU).METHODS:Baseline data of adult patients with CA who were admitted to the ICU from 2008 to 2019 were collected from the Medical Information Mart for Intensive Care(MIMIC)-IV.Patients were divided into survivor and non-survivor groups according to the 28-day prognosis.Serum concentrations of sodium,potassium,glucose,and urea nitrogen on the fi rst day of ICU admission were used to determine serum osmolarity.The primary endpoint of this study was 28-day all-cause mortality.Propensity score matching(PSM)analysis was performed to reduce bias between the survivor and nonsurvivor groups.RESULTS:Among the 798 included CA patients,the high osmolarity on the first day of ICU admission remained significantly associated with increased 28-day mortality(62.0%vs.35.5%,P<0.001)and reduced cumulative survival(log-rank P<0.05)after PSM.Cox regression identifi ed the high osmolarity on the fi rst day of ICU admission as an independent predictor.High serum osmolarity on the fi rst day of ICU admission eff ectively predicted 1-,3-,7-,and 28-day all-cause mortality,with the strongest predictive performance for 1-day mortality both before and after PSM(all P<0.05).CONCLUSION:In this study,elevated serum osmolarity on the first day of ICU admission was independently associated with increased 28-day mortality in CA patients and could serve as a prognostic marker.展开更多
In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electros...In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electrospun Poly(lactic-co-glycolic acid)/Gelatin(PLGA/Gel)membrane incorporated with Vascular Endothelial Growth Fac-tor(VEGF)and hawthorn extract.Functionally,the DP supplies native Extracellular Matrix(ECM)components and mechanical support,while PANINPs provide conductivity.The electrospun PLGA/Gel layer mimics fibrous ECM.It incorporates bioactives,with VEGF promoting pro-angiogenic stimulation and hawthorn extract enhanc-ing anticoagulant activity,as well as increasing surface hydrophilicity.The tissue adhesive ensures the interfacial integrity between the two layers.Decellularization efficiency was confirmed histologically using 4',6-diamidino-2-phenylindole(DAPI)and Hematoxylin-Eosin(H&E)staining.The DP exhibited a DNA content of 115.9±47.8 ng/mg DNA,compared to 982.88±395.42 ng/mg in Native Pericardium(NP).The PANINPs had an average par-ticle size of 104.94±13.7 nm.The conductivity of PANINPs-coated decellularized pericardium was measured to be 9.093±8.6×10-4 S/cm using the four-point probe method.PLGA/Gel membranes containing hawthorn extract(1%,5%,10%,and 15%w/v)and VEGF(0.1μg/mL,0.5μg/mL,and 1μg/mL)were fabricated by electrospinning,result-ing in fiber diameters between 850 and 1200 nm and pore sizes between 14 and 20μm.The anticoagulant efficiency of the membranes containing hawthorn extract reached 430 s in the Activated Partial Thromboplastin Time Assay(aPTT).Mechanical testing revealed a tensile strength of 22.70±6.33 MPa,an elongation of 53.58±10.63%,and Young's modulus of 0.67±0.10 MPa.The scaffold also exhibited over 91%cell viability and excellent cardiomyo-cyte adhesion.The hemolysis ratio was determined to be 0.421±0.191%,which confirms its blood compatibility.Our results indicate that the proposed bilayered scaffold can be a promising candidate for cardiac patch applications.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
Chronic heart failure(CHF) remains a global health challenge with limited therapeutic options. Mitochondrial dysfunction is a key pathological feature, and traditional Chinese medicine(TCM) shows unique potential in t...Chronic heart failure(CHF) remains a global health challenge with limited therapeutic options. Mitochondrial dysfunction is a key pathological feature, and traditional Chinese medicine(TCM) shows unique potential in targeting this mechanism. Evidence from human and animal models of heart failure indicates that TCM can restore mitochondrial function by regulating mitochondrial Ca^(2+) homeostasis, oxidative stress, energy metabolism, mitochondrial dynamics, and mitophagy. TCM-based treatment of CHF offers notable clinical advantages, including improved therapeutic efficacy, enhanced cardiac function, and reduced incidence of major cardiovascular events. Experimental studies demonstrate that TCM decoctions and monomers modulate signaling pathways such as PPAR–RXRα, NF-κB, and PI3K/AKT to alleviate oxidative stress. TCM also increases AMPK activity via phosphorylation of PGC-1α, indirectly promoting mitochondrial biogenesis;attenuates calcium influx and enhances Ca^(2+) reuptake, thereby ameliorating myocardial mitochondrial dysfunction in CHF;and improves CHF by rebalancing mitochondrial dynamics and autophagy.展开更多
Background:Pressure injury(PI)is a prevalent complication in pediatric cardiac surgery,with higher incidence than in general pediatric populations due to children’s thin skin,underdeveloped subcutaneous tissue,and pr...Background:Pressure injury(PI)is a prevalent complication in pediatric cardiac surgery,with higher incidence than in general pediatric populations due to children’s thin skin,underdeveloped subcutaneous tissue,and prolonged intraoperative pressure.Objective:To evaluate the effectiveness of the curvilinear supine position(CSP)in preventing PI among children undergoing congenital heart disease(CHD)surgery.Methods:Between October 2024 and February 2025,a single-center randomized controlled trial was conducted.Of the 80 children initially enrolled for congenital heart disease(CHD)surgery,77(aged 1 month to 14 years)completed the study and were included in the final analysis after 3 were excluded due to protocol violations.Participants were randomly assigned to the CSP group(n=38)or the conventional supine position group(n=39).Results:The incidence of PI was significantly lower in the CSP group(2.6%)compared to the control group(20.5%)(p=0.029).Postoperative LDH levels were also significantly reduced in the CSP group(422.67±86.52 U/L vs.592.92±215.71 U/L;p=0.031),while preoperative LDH and surgical variables(e.g.,cardiopulmonary bypass time)were comparable between groups.Although the CSP group had a shorter hospital stay(17.24 vs.22.51 days),the difference was not statistically significant(p=0.085).Caregiver satisfaction was significantly higher in the CSP group(100.0%vs.84.6%;p=0.025).Conclusion:CSP effectively reduces PI incidence,mitigates tissue injury,and enhances caregiver satisfaction in pediatric cardiac surgery,offering a safe and feasible strategy for perioperative PI prevention.展开更多
Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its prec...Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its precise mechanism in treating post-CHF cognitive dysfunction remains unclear.This study systematically investigates XJQ’s effects on post-CHF cognitive dysfunction and the underlying mechanisms.The components of XJQ were identified through liquid chromatography-mass spectrometry.CHF was induced in rats via ligation of the left anterior descending coronary artery,followed by six weeks of XJQ treatment.Cardiac function was evaluated through echocardiography and hemodynamic parameters,while cognitive function was assessed using Morris water maze(MWM)and open field tests(OFT).XJQ treatment enhanced both cardiac and cognitive functions in CHF rats.Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses,inflammation,and phosphodiesterase 4(PDE4)-dependent cyclic adenosine monophosphate(cAMP)signaling.XJQ inhibited microglial and astrocyte activation,decreased proinflammatory cytokines,and mitigated neuronal damage.Notably,XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP,protein kinase A(PKA),cAMP-response element binding protein(CREB),brain-derived neurotrophic factor(BDNF),PSD95,and synapsin I levels.Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin,kaempferol,isorhamnetin,and darutoside to PDE4.In conclusion,XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway.These findings provide valuable insight into the heart-brain axis.展开更多
BACKGROUND:To provide a comprehensive analysis of the landscape of artifi cial intelligence(AI)applications in cardiac arrest(CA).METHODS:Comprehensive searches were conducted in PubMed,the Cochrane Library,Webof Scie...BACKGROUND:To provide a comprehensive analysis of the landscape of artifi cial intelligence(AI)applications in cardiac arrest(CA).METHODS:Comprehensive searches were conducted in PubMed,the Cochrane Library,Webof Science,and EMBASE from database inception through 10 June 2025.Studies that applied AI inboth in-hospital cardiac arrest(IHCA)and out-of-hospital cardiac arrest(OHCA)populations acrossthe following domains were included:prediction of cardiac arrest occurrence,prognostication ofCA outcomes,applications of large language models(LLMs),and evaluation of cardiopulmonaryresuscitation(CPR)and other AI-driven interventions related to CA.RESULTS:The scoping review included 114 studies,encompassing data from 9,574,462patients in total.AI was most commonly applied to the prediction of CA(overall,n=40;IHCA,n=30;OHCA,n=4;and both,n=6),CPR-related decision support during CA(n=16),and post-arrestprognosis and rehabilitation outcomes(overall,n=38;OHCA,n=21;IHCA,n=3;and both,n=14).Additional application areas included LLM-based applications(n=8),emergency call handling(n=4),wearable device-based detection(n=3),heart rhythm identification(n=2),education(n=2),and extracorporeal cardiopulmonary resuscitation(ECPR)candidate identifi cation(n=1).Across allapplication scenarios,the highest area under the receiver operating characteristic curve(AUROC)value for pre-arrest CA prediction in IHCA patients was 0.998 using a multilayer perceptron(MLP)model,whereas the optimal AUROC for pre-arrest CA prediction in OHCA patients was 0.950 usingextreme gradient boosting(XGBoost)or random forest(RF)models.For CPR-related decisionsupport during CA,the highest AUROC achieved was 0.990 with a convolutional neural network(CNN)model.In prognostic prediction,the optimal AUROC for IHCA patients was 0.960 usingXGBoost,while for OHCA patients it reached 0.976 using an MLP model.CONCLUSION:This review shows that AI is most commonly used for the prediction of CA andCPR-related support,as well as post-arrest and rehabilitation outcomes.Future research directions includedrug discovery,post-resuscitation management,neurorehabilitation,and clinical trial innovation.Furtherstudies should prioritize multicenter clinical trials to evaluate AI models in real-world settings and validatetheir eff ectiveness across diverse patient populations.Overall,AI has signifi cant potential to improve clinicalpractice,and its role in CA application is increasingly important.展开更多
Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a n...Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a natural physical barrier against external interference.Our previous study established a dynamic culture system of the biofilm-state Bifidobacterium adolescentis Gr19(B-DC-B.adolescentis Gr19),forming higher density and more structurally stable biofilms,which enhanced its potential probiotic properties in vivo.Thus,the protective effect and mechanism of B-DC-B.adolescentis Gr19 on lipopolysaccharide(LPS)-induced intestinal barrier dysfunction were investigated in this study.The results showed that B-DC-B.adolescentis Gr19 not only had high resistance and adhesion activity,but also improved the intestinal barrier by increasing goblet cells and promoting the expression of tight junction(TJ)-related proteins.Moreover,B-DC-B.adolescentis Gr19 effectively attenuated intestinal barrier injury in Caco-2 cells by improving intestinal permeability and integrity.Remarkably,B-DC-B.adolescentis Gr19 enhanced expression of TJ proteins,restored localization of cytoskeleton and reduced intestinal inflammation by suppressing the Ras homolog family member A/Rho-associated coiled-coil-forming kinases/nuclear factor kappa B/myosin light chain kinase/myosin light chain(RhoA/ROCK/NF-κB/MLCK/MLC)pathway.Therefore,B-DC-B.adolescentis Gr19 plays a key role in mitigating LPS-induced intestinal barrier dysfunction.Overall,the present study provides a theoretical basis for ameliorating intestinal barrier dysfunction and developing novel functional foods by using biofilm-state probiotics under dynamic culture.展开更多
Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low...Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.展开更多
BACKGROUND:Sepsis is a prevalent and severe condition,with microcirculation disruptions playing a crucial role in its progression.Endothelial cell(EC)injury is the primary factor behind microcirculatory issues.This re...BACKGROUND:Sepsis is a prevalent and severe condition,with microcirculation disruptions playing a crucial role in its progression.Endothelial cell(EC)injury is the primary factor behind microcirculatory issues.This review is to outline the pathomechanism,organ heterogeneity,biomarkers,and therapeutic implications of endothelial dysfunction in sepsis,off ering references and insights for the clinical management of sepsis.METHODS:A systematic search of Web of Science and PubMed from inception to June 10,2025,limited to English publications,was conducted.Two reviewers independently identifi ed studies on EC injury in patients with septic microcirculatory dysfunction.Duplicate articles based on multiple search criteria were excluded.RESULTS:Fifty-nine articles,including cell,animal,and clinical studies,were included.These studies reported the effects of EC injury on the microcirculation in sepsis,including changes in vascular permeability,coagulation dysfunction,vasomotor regulation,and infl ammatory responses.These pathways interact and ultimately lead to septic microcirculation disorders.CONCLUSION:Sepsis-induced endothelial dysfunction involves various interconnected mechanisms,which collectively compromise ECs and impede microcirculatory perfusion.Future research should enhance current understanding of endothelial injury mechanisms,develop synergistic multi-target strategies to disrupt this cycle,and facilitate the clinical application of endothelial markers for early intervention and dynamic assessment.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82430018 to Q.C.,82270361 and 82570402 to H.Z.)the Nanjing Medical University Undergraduate Innovation and Entrepreneurship Training Program Fund(Grant No.202410312138Y to C.Z.)the Basic Sciences of Jiangsu Higher Education Institutions(Grant No.22KJA310002 to H.Z.)。
文摘As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovascular health.This study explores the association between MASLD-related liver fibrosis and cardiac dysfunction,focusing on how liver fibrosis contributes to cardiac remodeling and dysfunction.Cernea et al’s research highlights the strong correlation between liver fibrosis and changes in left ventricular mass,left atrial dimensions,and systolic and diastolic function in diabetic patients.Notably,the study suggests a protective role of sex-hormone binding protein against cardiac remodeling.These findings underline the importance of early detection of liver fibrosis using noninvasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores,which may offer dual protection for both liver and heart health in T2DM patients.Moreover,this study calls for further research into the shared pathogenic mechanisms,including inflammation and fibrosis pathways,between the liver and heart.It advocates for the integration of liver fibrosis screening into cardiovascular risk management,urging clinicians to adopt a more holistic approach in treating patients with MASLD and T2DM.The research has broad implications for preventing cardiovascular complications and improving outcomes in this highrisk population.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金supported by the National High Level Hospital Clinical Research Funding (2022-NHLHCRF-YS-03)the National Natural Science Foundation of China (82272196)。
文摘BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.
文摘Objective:To investigate the effect of 12-lead electrocardiogram and 24-hour dynamic electrocardiogram in detecting pacemaker dysfunction and changes in cardiac function indexes in patients with pacemaker implantation.Methods:A total of 136 patients with pacemaker implantation in the First Clinical Medical College of Three Gorges University,Institute of Cardiovascular Disease of Three Gorges University and Yicang Central People’s Hospital from January 2023 to December 2024 were selected as the research objects.All patients received 12-lead electrocardiogram and 24-hour holter 3–14 days after implantation.Results:The overall detection rate of various types of pacemaker dysfunction by Holter was significantly higher than that by conventional ECG(27.21%vs.5.15%,χ^(2)=24.402,P<0.001).The overall arrhythmia detection rate of Holter was significantly higher than that of conventional electrocardiogram(57.35%vs.10.29%,χ^(2)=67.277,P<0.001).The time domain indexes of heart rate variability obtained by 24-hour continuous monitoring of Holter were significantly improved compared with those of conventional electrocardiogram(P<0.05).Conclusions:Compared with 12-lead electrocardiogram,24-hour holter monitoring can more accurately detect pacemaker dysfunction and arrhythmia in patients with pacemaker implantation,and provide more comprehensive data of heart rate variability,which is helpful for clinicians to better evaluate the cardiac function of patients and adjust treatment plans.
基金Supported by the Special Project for Supporting the Development of Biomedicine and Health Industry in Hangzhou City,No.2022WJC123Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project,No.2022ZA143.
文摘BACKGROUND Long-term antipsychotic therapy in psychiatric patients carries significant cardiovascular risks,including QT interval prolongation,myocardial injury,and functional impairment.Guanxinning,a traditional Chinese medicine formulation,has demonstrated cardioprotective potential in preclinical studies,but clinical evidence in this population remains limited.AIM To evaluate the cardioprotective effects of Guanxinning against antipsychotic-induced cardiac injury in long-term hospitalized psychiatric patients.METHODS A randomized,double-blind,placebo-controlled trial was conducted with 120 psychiatric inpatients receiving chronic antipsychotic therapy.Participants were allocated to:Intervention group:Conventional antipsychotics+Guanxinning tablets(0.38 g×4 tablets,ter in die);Control group:Conventional antipsychotics+identical placebo;Cardiac assessments at baseline and 12 months included:Electrocardiography(corrected QT interval),echocardiography(left ventricular ejection fraction,left ventricular end-diastolic diameter),serum biomarkers(cardiac troponin I,B-type natriuretic peptide,superoxide dismutase,malondialdehyde,high-sensitivity C-reactive protein).RESULTS Compared to controls,the Guanxinning group showed:Electrophysiological improvement:Corrected QT shortening(438±25 milliseconds vs 465±30 milliseconds,P<0.01).Functional enhancement:Left ventricular ejection fraction increase(58.5%±5.2%vs 53.8%±4.8%,P<0.05),left ventricular end-diastolic diameter reduction(49.8±3.5 mm vs 52.6±3.8 mm,P<0.05),Biochemical modulation:Reduced myocardial injury markers(cardiac troponin I:0.009 ng/mL vs 0.014 ng/mL;B-type natriuretic peptide:52 pg/mL vs 78 pg/mL,P<0.001),improved oxidative stress(superoxide dismutase:↑13.3 U/mL;malondialdehyde:↓0.9 nmol/mL,P<0.001),attenuated inflammation(high-sensitivity C-reactive protein:2.0 mg/L vs 3.2 mg/L,P<0.001).CONCLUSION Guanxinning significantly mitigates antipsychotic-induced cardiac injury in psychiatric patients,demonstrating:Normalization of electrophysiological parameters,Preservation of systolic/diastolic function,suppression of oxidative stress and inflammation.These findings support its clinical application as an adjunctive cardioprotective therapy,potentially through inhibition of myocardial apoptosis and antioxidant upregulation.
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN).
文摘Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.
基金supported by the Innovation Promotion Program of NHC and Shanghai Key Labs,SIBPT(grant number PT2025-01)。
文摘Human cardiac organoids have revolutionized the study of cardiac development,disease modeling, drug discovery, and regenerative therapies. This review systematically discusses strategies and progress in the construction of cardiac organoids, categorizing them into three main types:cardiac spheroids, self-organizing/assembloid organoids, and organoid-on-a-chip systems. This review uniquely integrates the advances in vascularization, organ-on-chip design, and environmental cardiotoxicity modeling within cardiac organoid platforms, offering a critical synthesis that is absent in the literature. In the context of escalating environmental threats to cardiovascular health, there is an urgent need for physiologically relevant models to accurately identify cardiac toxicants and elucidate their underlying mechanisms of action. This review highlights advances in cardiac organoid applications for disease modeling-including congenital heart defects and acquired cardiovascular diseases-drug development, toxicity screening, and the study of environmentally induced cardiovascular pathogenesis. In addition, it critically examines ongoing challenges and underscores opportunities brought by bioengineering approaches. Finally, we propose future directions for developing standardized cardiac organoid platforms with clinical predictability, aiming to expand the utility of this technology across broader research applications.
基金supported by China Scholarship Council(No.202106380078 to HL)the Netherlands Cardiovascular Research Initiative:The Dutch Heart Foundation(CVON 2018-28 and 2012-06 Heart Brain Connection to AMT)。
文摘Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).
基金National Key Research and Development Program of China,Grant/Award Number:2021YFF0702200Science and Technology Projects in Guangzhou,Grant/Award Number:202206010084,202206010197 and 202206060002+1 种基金Guangdong S&T programme,Grant/Award Number:2009A081000002 and 2023B0303040004Technology Planning Project of Linzhi,Grant/Award Number:2023-YZ-01。
文摘Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.
基金funded by the Shenzhen Science and Technology Program(JCYJ20230807112007014 to PG)the Shenzhen Key Medical Discipline Construction Fund(SZXK046 to PG).
文摘BACKGROUND:Serum osmolality is a prognostic indicator in critically ill patients.This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest(CA)admitted to the intensive care unit(ICU).METHODS:Baseline data of adult patients with CA who were admitted to the ICU from 2008 to 2019 were collected from the Medical Information Mart for Intensive Care(MIMIC)-IV.Patients were divided into survivor and non-survivor groups according to the 28-day prognosis.Serum concentrations of sodium,potassium,glucose,and urea nitrogen on the fi rst day of ICU admission were used to determine serum osmolarity.The primary endpoint of this study was 28-day all-cause mortality.Propensity score matching(PSM)analysis was performed to reduce bias between the survivor and nonsurvivor groups.RESULTS:Among the 798 included CA patients,the high osmolarity on the first day of ICU admission remained significantly associated with increased 28-day mortality(62.0%vs.35.5%,P<0.001)and reduced cumulative survival(log-rank P<0.05)after PSM.Cox regression identifi ed the high osmolarity on the fi rst day of ICU admission as an independent predictor.High serum osmolarity on the fi rst day of ICU admission eff ectively predicted 1-,3-,7-,and 28-day all-cause mortality,with the strongest predictive performance for 1-day mortality both before and after PSM(all P<0.05).CONCLUSION:In this study,elevated serum osmolarity on the first day of ICU admission was independently associated with increased 28-day mortality in CA patients and could serve as a prognostic marker.
文摘In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electrospun Poly(lactic-co-glycolic acid)/Gelatin(PLGA/Gel)membrane incorporated with Vascular Endothelial Growth Fac-tor(VEGF)and hawthorn extract.Functionally,the DP supplies native Extracellular Matrix(ECM)components and mechanical support,while PANINPs provide conductivity.The electrospun PLGA/Gel layer mimics fibrous ECM.It incorporates bioactives,with VEGF promoting pro-angiogenic stimulation and hawthorn extract enhanc-ing anticoagulant activity,as well as increasing surface hydrophilicity.The tissue adhesive ensures the interfacial integrity between the two layers.Decellularization efficiency was confirmed histologically using 4',6-diamidino-2-phenylindole(DAPI)and Hematoxylin-Eosin(H&E)staining.The DP exhibited a DNA content of 115.9±47.8 ng/mg DNA,compared to 982.88±395.42 ng/mg in Native Pericardium(NP).The PANINPs had an average par-ticle size of 104.94±13.7 nm.The conductivity of PANINPs-coated decellularized pericardium was measured to be 9.093±8.6×10-4 S/cm using the four-point probe method.PLGA/Gel membranes containing hawthorn extract(1%,5%,10%,and 15%w/v)and VEGF(0.1μg/mL,0.5μg/mL,and 1μg/mL)were fabricated by electrospinning,result-ing in fiber diameters between 850 and 1200 nm and pore sizes between 14 and 20μm.The anticoagulant efficiency of the membranes containing hawthorn extract reached 430 s in the Activated Partial Thromboplastin Time Assay(aPTT).Mechanical testing revealed a tensile strength of 22.70±6.33 MPa,an elongation of 53.58±10.63%,and Young's modulus of 0.67±0.10 MPa.The scaffold also exhibited over 91%cell viability and excellent cardiomyo-cyte adhesion.The hemolysis ratio was determined to be 0.421±0.191%,which confirms its blood compatibility.Our results indicate that the proposed bilayered scaffold can be a promising candidate for cardiac patch applications.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
基金supported by the National Natural Science Foundation of China (No. 82374195)。
文摘Chronic heart failure(CHF) remains a global health challenge with limited therapeutic options. Mitochondrial dysfunction is a key pathological feature, and traditional Chinese medicine(TCM) shows unique potential in targeting this mechanism. Evidence from human and animal models of heart failure indicates that TCM can restore mitochondrial function by regulating mitochondrial Ca^(2+) homeostasis, oxidative stress, energy metabolism, mitochondrial dynamics, and mitophagy. TCM-based treatment of CHF offers notable clinical advantages, including improved therapeutic efficacy, enhanced cardiac function, and reduced incidence of major cardiovascular events. Experimental studies demonstrate that TCM decoctions and monomers modulate signaling pathways such as PPAR–RXRα, NF-κB, and PI3K/AKT to alleviate oxidative stress. TCM also increases AMPK activity via phosphorylation of PGC-1α, indirectly promoting mitochondrial biogenesis;attenuates calcium influx and enhances Ca^(2+) reuptake, thereby ameliorating myocardial mitochondrial dysfunction in CHF;and improves CHF by rebalancing mitochondrial dynamics and autophagy.
文摘Background:Pressure injury(PI)is a prevalent complication in pediatric cardiac surgery,with higher incidence than in general pediatric populations due to children’s thin skin,underdeveloped subcutaneous tissue,and prolonged intraoperative pressure.Objective:To evaluate the effectiveness of the curvilinear supine position(CSP)in preventing PI among children undergoing congenital heart disease(CHD)surgery.Methods:Between October 2024 and February 2025,a single-center randomized controlled trial was conducted.Of the 80 children initially enrolled for congenital heart disease(CHD)surgery,77(aged 1 month to 14 years)completed the study and were included in the final analysis after 3 were excluded due to protocol violations.Participants were randomly assigned to the CSP group(n=38)or the conventional supine position group(n=39).Results:The incidence of PI was significantly lower in the CSP group(2.6%)compared to the control group(20.5%)(p=0.029).Postoperative LDH levels were also significantly reduced in the CSP group(422.67±86.52 U/L vs.592.92±215.71 U/L;p=0.031),while preoperative LDH and surgical variables(e.g.,cardiopulmonary bypass time)were comparable between groups.Although the CSP group had a shorter hospital stay(17.24 vs.22.51 days),the difference was not statistically significant(p=0.085).Caregiver satisfaction was significantly higher in the CSP group(100.0%vs.84.6%;p=0.025).Conclusion:CSP effectively reduces PI incidence,mitigates tissue injury,and enhances caregiver satisfaction in pediatric cardiac surgery,offering a safe and feasible strategy for perioperative PI prevention.
基金supported by the National Natural Science Foundation of China(Nos.82430116 and 82574622)the Special Fund of Central Committee High Level Chinese Medicine Hospital(Nos.DZMG-LJRC-0014,DZMG-ZJXY-23013)+1 种基金Chinese Medicine Inheritance and Innovation“Thousand Million”Talents Project(Qihuang Project 2021)Qihuang Scholarsthe Medical and Health Industry Development Project of Tongzhou District(2023).
文摘Chronic heart failure(CHF)impairs cognitive function.Xijiaqi Formula(XJQ),a traditional Chinese medicine(TCM)used clinically to treat CHF,demonstrates potential for improving cognition in CHF patients.However,its precise mechanism in treating post-CHF cognitive dysfunction remains unclear.This study systematically investigates XJQ’s effects on post-CHF cognitive dysfunction and the underlying mechanisms.The components of XJQ were identified through liquid chromatography-mass spectrometry.CHF was induced in rats via ligation of the left anterior descending coronary artery,followed by six weeks of XJQ treatment.Cardiac function was evaluated through echocardiography and hemodynamic parameters,while cognitive function was assessed using Morris water maze(MWM)and open field tests(OFT).XJQ treatment enhanced both cardiac and cognitive functions in CHF rats.Network pharmacology identified 12 core active components of XJQ and indicated its effect on cognitive dysfunction involved regulating synapses,inflammation,and phosphodiesterase 4(PDE4)-dependent cyclic adenosine monophosphate(cAMP)signaling.XJQ inhibited microglial and astrocyte activation,decreased proinflammatory cytokines,and mitigated neuronal damage.Notably,XJQ promoted synaptic repair and dendritic growth by downregulating PDE4 and upregulating cAMP,protein kinase A(PKA),cAMP-response element binding protein(CREB),brain-derived neurotrophic factor(BDNF),PSD95,and synapsin I levels.Molecular docking and Bio-layer interferometry assays confirmed direct binding of quercetin,kaempferol,isorhamnetin,and darutoside to PDE4.In conclusion,XJQ alleviates neuroinflammation and enhances synaptic plasticity to improve cognitive dysfunction in CHF rats via the PDE4/cAMP/PKA/CREB signaling pathway.These findings provide valuable insight into the heart-brain axis.
基金supported by grant from the National Natural Science Foundation of China(82372207).
文摘BACKGROUND:To provide a comprehensive analysis of the landscape of artifi cial intelligence(AI)applications in cardiac arrest(CA).METHODS:Comprehensive searches were conducted in PubMed,the Cochrane Library,Webof Science,and EMBASE from database inception through 10 June 2025.Studies that applied AI inboth in-hospital cardiac arrest(IHCA)and out-of-hospital cardiac arrest(OHCA)populations acrossthe following domains were included:prediction of cardiac arrest occurrence,prognostication ofCA outcomes,applications of large language models(LLMs),and evaluation of cardiopulmonaryresuscitation(CPR)and other AI-driven interventions related to CA.RESULTS:The scoping review included 114 studies,encompassing data from 9,574,462patients in total.AI was most commonly applied to the prediction of CA(overall,n=40;IHCA,n=30;OHCA,n=4;and both,n=6),CPR-related decision support during CA(n=16),and post-arrestprognosis and rehabilitation outcomes(overall,n=38;OHCA,n=21;IHCA,n=3;and both,n=14).Additional application areas included LLM-based applications(n=8),emergency call handling(n=4),wearable device-based detection(n=3),heart rhythm identification(n=2),education(n=2),and extracorporeal cardiopulmonary resuscitation(ECPR)candidate identifi cation(n=1).Across allapplication scenarios,the highest area under the receiver operating characteristic curve(AUROC)value for pre-arrest CA prediction in IHCA patients was 0.998 using a multilayer perceptron(MLP)model,whereas the optimal AUROC for pre-arrest CA prediction in OHCA patients was 0.950 usingextreme gradient boosting(XGBoost)or random forest(RF)models.For CPR-related decisionsupport during CA,the highest AUROC achieved was 0.990 with a convolutional neural network(CNN)model.In prognostic prediction,the optimal AUROC for IHCA patients was 0.960 usingXGBoost,while for OHCA patients it reached 0.976 using an MLP model.CONCLUSION:This review shows that AI is most commonly used for the prediction of CA andCPR-related support,as well as post-arrest and rehabilitation outcomes.Future research directions includedrug discovery,post-resuscitation management,neurorehabilitation,and clinical trial innovation.Furtherstudies should prioritize multicenter clinical trials to evaluate AI models in real-world settings and validatetheir eff ectiveness across diverse patient populations.Overall,AI has signifi cant potential to improve clinicalpractice,and its role in CA application is increasingly important.
基金funded by Beijing Natural Science Foundation(6252001)Guangdong Basic and Applied Basic Research Foundation(2022A1515140021)Natural Science Foundation of China(31871772).
文摘Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a natural physical barrier against external interference.Our previous study established a dynamic culture system of the biofilm-state Bifidobacterium adolescentis Gr19(B-DC-B.adolescentis Gr19),forming higher density and more structurally stable biofilms,which enhanced its potential probiotic properties in vivo.Thus,the protective effect and mechanism of B-DC-B.adolescentis Gr19 on lipopolysaccharide(LPS)-induced intestinal barrier dysfunction were investigated in this study.The results showed that B-DC-B.adolescentis Gr19 not only had high resistance and adhesion activity,but also improved the intestinal barrier by increasing goblet cells and promoting the expression of tight junction(TJ)-related proteins.Moreover,B-DC-B.adolescentis Gr19 effectively attenuated intestinal barrier injury in Caco-2 cells by improving intestinal permeability and integrity.Remarkably,B-DC-B.adolescentis Gr19 enhanced expression of TJ proteins,restored localization of cytoskeleton and reduced intestinal inflammation by suppressing the Ras homolog family member A/Rho-associated coiled-coil-forming kinases/nuclear factor kappa B/myosin light chain kinase/myosin light chain(RhoA/ROCK/NF-κB/MLCK/MLC)pathway.Therefore,B-DC-B.adolescentis Gr19 plays a key role in mitigating LPS-induced intestinal barrier dysfunction.Overall,the present study provides a theoretical basis for ameliorating intestinal barrier dysfunction and developing novel functional foods by using biofilm-state probiotics under dynamic culture.
基金supported by China International Medical Foundation(Z-2019-42-1908-4)Natural Science Basic Research Program of Shaanxi Province(2019JM-440).
文摘Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.
文摘BACKGROUND:Sepsis is a prevalent and severe condition,with microcirculation disruptions playing a crucial role in its progression.Endothelial cell(EC)injury is the primary factor behind microcirculatory issues.This review is to outline the pathomechanism,organ heterogeneity,biomarkers,and therapeutic implications of endothelial dysfunction in sepsis,off ering references and insights for the clinical management of sepsis.METHODS:A systematic search of Web of Science and PubMed from inception to June 10,2025,limited to English publications,was conducted.Two reviewers independently identifi ed studies on EC injury in patients with septic microcirculatory dysfunction.Duplicate articles based on multiple search criteria were excluded.RESULTS:Fifty-nine articles,including cell,animal,and clinical studies,were included.These studies reported the effects of EC injury on the microcirculation in sepsis,including changes in vascular permeability,coagulation dysfunction,vasomotor regulation,and infl ammatory responses.These pathways interact and ultimately lead to septic microcirculation disorders.CONCLUSION:Sepsis-induced endothelial dysfunction involves various interconnected mechanisms,which collectively compromise ECs and impede microcirculatory perfusion.Future research should enhance current understanding of endothelial injury mechanisms,develop synergistic multi-target strategies to disrupt this cycle,and facilitate the clinical application of endothelial markers for early intervention and dynamic assessment.
