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
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
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
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)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
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
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
Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apop...Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.展开更多
Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significa...Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.展开更多
Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables th...Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resu...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.展开更多
Diabetic cardiomyopathy(DCM)has long been considered as a left ventricular(LV)disease with diastolic dysfunction preceding systolic dysfunction in diabetes.However,it is increasingly recognized that the right ventricl...Diabetic cardiomyopathy(DCM)has long been considered as a left ventricular(LV)disease with diastolic dysfunction preceding systolic dysfunction in diabetes.However,it is increasingly recognized that the right ventricle(RV)is also affected by diabetes and may be independently responsible for adverse outcomes in diabetic patients with or without LV failure.Yu et al conducted a 30-week longitudinal evaluation of biventricular function and pathology in OVE26 diabetic mice and revealed early diastolic dysfunction preceding systolic decline,suggesting that early LV diastolic impairment precedes the later onset of systolic dysfunction.With age,the animals developed fibrosis,hypertrophy,and pulmonary arterial hypertension in the RV.The purpose of this editorial is to contextualize these findings within the existing literature by highlighting the interplay between cardiac chambers and the vasculature.We also seek to reiterate that DCM is a condition extending beyond left ventricular dysfunction.As the authors note,the right side of the heart may remain"the forgotten ventricle"in diabetic patients.We hope that the mechanisms discussed in this paper will help researchers to understand the pathogenesis of cardiovascular disease in this context and encourage clinicians to be more attentive to the associated clinical symptoms.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related mortality worldwide.This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms,wi...Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related mortality worldwide.This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms,with a particular focus on mitochondrial function and apoptosis.Methods:Differential expression analyses were performed across three datasets—The Cancer Genome Atlas(TCGA)-Liver Hepatocellular Carcinoma(LIHC),GSE36076,and GSE95698—to identify overlapping differentially expressed genes(DEGs).A prognostic risk model was then constructed.Cysteine/serine-rich nuclear protein 1(CSRNP1)expression levels in HCC cell lines were assessed via western blot(WB)and quantitative reverse transcription polymerase chain reaction(qRT-PCR).The effects of CSRNP1 knockdown or overexpression on cell proliferation,migration,and apoptosis were evaluated using cell counting-8(CCK-8)assays,Transwell assays,and flow cytometry.Mitochondrial ultrastructure was examined by transmission electron microscopy,and intracellular and mitochondrial reactive oxygen species(mROS)levels were measured using specific fluorescent probes.WB was used to assess activation of the c-Jun N-terminal kinase(JNK)/p38 mitogen-activated protein kinase(MAPK)pathway,and pathway dependence was examined using the ROS scavenger N-Acetylcysteine(NAC)and the JNK inhibitor SP600125.Results:A six-gene prognostic model was established,comprising downregulated genes(NR4A1 and CSRNP1)and upregulated genes(CENPQ,YAE1,FANCF,and POC5)in HCC.Functional experiments revealed that CSRNP1 knockdown promoted the proliferation of HCC cells and suppressed their apoptosis.Conversely,CSRNP1 overexpression impaired mitochondrial integrity,increased both mitochondrial and cytoplasmic ROS levels,and activated the JNK/p38 MAPK pathway.Notably,treatment with NAC or SP600125 attenuated CSRNP1-induced MAPK activation and apoptosis.Conclusion:CSRNP1 is a novel prognostic biomarker and tumor suppressor in HCC.It exerts anti-tumor effects by inducing oxidative stress and activating the JNK/p38 MAPK pathway in a ROS-dependent manner.These findings suggest that CSRNP1 may serve as a potential therapeutic target in the management of HCC.展开更多
BACKGROUND Global longitudinal strain(GLS)of the left ventricular is a highly sensitive and reliable marker of systolic function and GLS outperforms ejection fraction(EF)in detecting preclinical left ventricular systo...BACKGROUND Global longitudinal strain(GLS)of the left ventricular is a highly sensitive and reliable marker of systolic function and GLS outperforms ejection fraction(EF)in detecting preclinical left ventricular systolic dysfunction(LVSD).In patients with type 2 diabetes(DM2)albuminuria is a predictor of symptomatic heart failure,but data on the relationship between GLS and albuminuria are conflicting.AIM To explore the relationship between GLS and albuminuria in a contemporary cohort of DM2 patients.METHODS The study was performed on DM2 patients consecutively enrolled in the TESEO study.Patients with symptoms/signs of heart failure,EF<50%,coronary artery,other cardiac diseases,or non-adequate acoustic window for GLS assessment were excluded.We collected clinical data,screened for complications,and measured GLS by speckle-tracking echocardiography.Univariate and multiple linear regression analyses were performed to identify independent explanatory variables associated with GLS.Logistic regression analysis was used to assess whether albuminuria was independently associated with GLS-diagnosed(GLS>-18%)LVSD.RESULTS Patients(n=193,age:60.6±8.1,male:57%)had a short DM2 duration(3.8±4.9 years)and good metabolic control(glycated haemoglobin A1c:6.5%±1.0).Preclinical GLS-LVSD was present in 21.8%of the patients.GLS values were significantly higher in patients with albuminuria(-19.88±2.16 vs-18.29±2.99,P<0.001)and in multivariate analysis natural logarithm of albumin-creatinine ratio and uric acid were independent predictors of GLS.In logistic regression analysis,albuminuria was associated with a 6.01(95%confidence interval:1.874-19.286)increased odds ratio of GLS-LVSD,independent of age,sex,diastolic blood pressure,chronic kidney disease,EF,mitral annulus velocity lateral,uric acid,and treatments.CONCLUSION Albuminuria was independently associated with subclinical LVSD in our contemporary cohort of DM2 patients.展开更多
Left ventricular diastolic dysfunction is frequently noticed in patients with chronic kidney disease.Echocardiography is used to determine the presence and severity of diastolic dysfunction.In left ventricular diastol...Left ventricular diastolic dysfunction is frequently noticed in patients with chronic kidney disease.Echocardiography is used to determine the presence and severity of diastolic dysfunction.In left ventricular diastolic dysfunction the ventricular diastolic distensibility,filling or relaxation is abnormal;however,the left ventricular ejection fraction may be normal or decreased.In heart failure with preserved ejection fraction,the patients have symptomatic pulmonary congestion even though the systolic ejection fraction is more than 50%.This condition is commonly associated with ventricular diastolic dysfunction.Increased incidence of major adverse cardiovascular events has been reported in surgical patients having grade III diastolic dysfunction.Peri-operatively haemodynamic instability and fluid overload in this set of patients is known to generate pulmonary oedema.展开更多
The feasibility and safety of total arterial coronary revascularization with 2 arterial conduits in patients with impaired left ventricular function was evaluated. Data were prospectively collected on all patients wit...The feasibility and safety of total arterial coronary revascularization with 2 arterial conduits in patients with impaired left ventricular function was evaluated. Data were prospectively collected on all patients with multiple vessel disease and moderately or severely impaired left ventricular function, who underwent coronary surgery with the intention of total arterial revascularization with 2 conduits between March 1995 and August 2002. One hundred and seventy-nine patients were included in the study. Acute coronary insufficiency was present in 3 patients and 43 had unstable angina. Severe left ventricular impairment was present in 29 patients. There were 17 redo operations including 3 redo-redo procedures. Eighty-two percent of patients had a Y graft configuration from the left internal mammary artery （right internal mammary artery 40. 8 %, radial artery 33. 5 %, other 7.8 % ）. The perioperative mortality was 2. 2 %, myocardial infarction 1.7 % and stroke 0. 6 %. Total arterial revascularization in patients with ischaemic left ventricular dysfunction can be safely performed with 2 arterial conduits. The radial artery provides conduit length greater than the right internal mammary artery and allows full revascularization despite left ventricular dilatation.展开更多
BACKGROUND Liver cirrhosis is a chronic hepatic disease which is associated with cardiovascular abnormalities.Hyperdynamic circulation in liver cirrhosis causes functional and structural cardiac alterations.The preval...BACKGROUND Liver cirrhosis is a chronic hepatic disease which is associated with cardiovascular abnormalities.Hyperdynamic circulation in liver cirrhosis causes functional and structural cardiac alterations.The prevalence of left ventricle diastolic dysfunction(LVDD)in cirrhotic patients ranges from 25.7%to as high as 81.4%as reported in different studies.In several studies the severity of diastolic dysfunction(DD)correlated with a degree of liver failure and the rate of dysfunction was higher in patients with decompensated cirrhosis compared with compensated.Future directions of comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients.AIM To clarify the correlation between the severity of liver cirrhosis and left ventricle diastolic dysfunction in the existing literature.METHODS Through January and February of 2019 at Vilnius University we conducted a systematic review of the global existing literature on the prevalence of left ventricle diastolic dysfunction in patients with liver cirrhosis.We searched for articles in PubMed,Medline and Web of science databases.Articles were selected by using adequate inclusion and exclusion criteria.Our interest was the outcome of likely correlation between the severity of cirrhosis[evaluated by Child-Pugh classes,Model For End-Stage Liver Disease(MELD)scores]and left ventricle diastolic dysfunction[classified according to American Society of Echocardiography(ASE)guidelines(2009,2016)],as well as relative risk of dysfunction in cirrhotic patients.Subgroup analyses were performed to evaluate the ratio and grades of left ventricle diastolic dysfunction with respect to cirrhosis severity.RESULTS A total of 1149 articles and abstracts met the initial search criteria.Sixteen articles which met the predefined eligibility criteria were included in the final analysis.Overall,1067 patients(out of them 723 men)with liver cirrhosis were evaluated for left ventricle diastolic dysfunction.In our systemic analysis we have found that 51.2%of cirrhotic patients had left ventricle diastolic dysfunction diagnosed and the grade 1 was the most prevalent(59.2%,P<0.001)among them,the grade 3 had been rarely diagnosed-only 5.1%.The data about the prevalence of diastolic dysfunction in cirrhotic patients depending on Child-Pugh Classes was available from 5 studies(365 patients overall)and only in 1 research diastolic dysfunction was found being associated with severity of liver cirrhosis(P<0.005).We established that diastolic dysfunction was diagnosed in 44.6%of Child-Pugh A class patients,in 62%of Child B class and in 63.3%of Child C patients(P=0.028).The proportion of patients with higher diastolic dysfunction grades increases in more severe cirrhosis presentation(P<0.001).There was no difference between mean MELD scores in patients with and without diastolic dysfunction and in different diastolic dysfunction groups.In all studies diastolic dysfunction was more frequent in patients with ascites.CONCLUSION This systemic analysis suggests that left ventricle diastolic dysfunction is an attribute of liver cirrhosis which has not received sufficient attention from clinicians so far.Future suggestions of a comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients and give hint for better understanding of the left ventricle diastolic dysfunction pathogenesis in liver cirrhosis.展开更多
Background Heart failure(HF)is a leading cause of hospitalization and mortality for older chronic kidney disease(CKD)patients.However,the epidemiological data is scarce.We aimed to determine the prevalence of left ven...Background Heart failure(HF)is a leading cause of hospitalization and mortality for older chronic kidney disease(CKD)patients.However,the epidemiological data is scarce.We aimed to determine the prevalence of left ventricular(LV)dysfunction and HF,and to explore the risk factors for HF among those patients.Methods This is a cross-sectional analysis of the China Hypertension Survey conducted between October 2012 and December 2015.A total of 5,808 participants aged≥65 years were included in the analysis.Self-reported history of HF and any other cardiovascular diseases was acquired.2-D and Doppler echocardiography were used to assess LV dysfunction.CKD was defined as either estimated glomerular filtration rate(eGFR)<60 mL/min per 1.73 m2 or urinary albumin to creatinine ratio(ACR)≥30 mg/g.Results Among CKD patients aged≥65 years,the weighted prevalence of HF,heart failure with preserved ejection fraction(HFpEF),heart failure with mid-range ejection fraction(HFmrEF),and heart failure with reduced ejection fraction(HFrEF)was 4.8%,2.5%,0.8%,and 1.7%,respectively.The weighted prevalence of HF was 5.0%in patients with eGFR<60 mL/min per 1.73 m2,and was 5.9%in patients with ACR≥30 mg/g.The prevalence of LV systolic dysfunction was 3.1%,and while it was 8.9%for moderate/severe diastolic dysfunction.Multivariate analysis showed that smoking was significantly associated with the risk of HF.Furthermore,age,smoking,and residents in rural areas were significantly associated with a risk of LV diastolic dysfunction.Conclusions The prevalence of HF and LV dysfunction was high in older patients with CKD,suggesting that particular strategies will be required.展开更多
BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomy...BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.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.
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 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(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.
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.
基金supported by the National Natural Science Foundation of China,No.82204663(to TZ)the Natural Science Foundation of Shandong Province,No.ZR2022QH058(to TZ).
文摘Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.
文摘Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.
文摘Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.
文摘Diabetic cardiomyopathy(DCM)has long been considered as a left ventricular(LV)disease with diastolic dysfunction preceding systolic dysfunction in diabetes.However,it is increasingly recognized that the right ventricle(RV)is also affected by diabetes and may be independently responsible for adverse outcomes in diabetic patients with or without LV failure.Yu et al conducted a 30-week longitudinal evaluation of biventricular function and pathology in OVE26 diabetic mice and revealed early diastolic dysfunction preceding systolic decline,suggesting that early LV diastolic impairment precedes the later onset of systolic dysfunction.With age,the animals developed fibrosis,hypertrophy,and pulmonary arterial hypertension in the RV.The purpose of this editorial is to contextualize these findings within the existing literature by highlighting the interplay between cardiac chambers and the vasculature.We also seek to reiterate that DCM is a condition extending beyond left ventricular dysfunction.As the authors note,the right side of the heart may remain"the forgotten ventricle"in diabetic patients.We hope that the mechanisms discussed in this paper will help researchers to understand the pathogenesis of cardiovascular disease in this context and encourage clinicians to be more attentive to the associated clinical symptoms.
基金funded by Shanghai Yangpu District Science and Technology Commission(Grant No.YPQ202303(Xuejing Lin))Shanghai Yangpu Hospital Foundation(Grant No.Se1202420(Wenchao Wang)and Ye1202423(Juan Huang)).
文摘Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related mortality worldwide.This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms,with a particular focus on mitochondrial function and apoptosis.Methods:Differential expression analyses were performed across three datasets—The Cancer Genome Atlas(TCGA)-Liver Hepatocellular Carcinoma(LIHC),GSE36076,and GSE95698—to identify overlapping differentially expressed genes(DEGs).A prognostic risk model was then constructed.Cysteine/serine-rich nuclear protein 1(CSRNP1)expression levels in HCC cell lines were assessed via western blot(WB)and quantitative reverse transcription polymerase chain reaction(qRT-PCR).The effects of CSRNP1 knockdown or overexpression on cell proliferation,migration,and apoptosis were evaluated using cell counting-8(CCK-8)assays,Transwell assays,and flow cytometry.Mitochondrial ultrastructure was examined by transmission electron microscopy,and intracellular and mitochondrial reactive oxygen species(mROS)levels were measured using specific fluorescent probes.WB was used to assess activation of the c-Jun N-terminal kinase(JNK)/p38 mitogen-activated protein kinase(MAPK)pathway,and pathway dependence was examined using the ROS scavenger N-Acetylcysteine(NAC)and the JNK inhibitor SP600125.Results:A six-gene prognostic model was established,comprising downregulated genes(NR4A1 and CSRNP1)and upregulated genes(CENPQ,YAE1,FANCF,and POC5)in HCC.Functional experiments revealed that CSRNP1 knockdown promoted the proliferation of HCC cells and suppressed their apoptosis.Conversely,CSRNP1 overexpression impaired mitochondrial integrity,increased both mitochondrial and cytoplasmic ROS levels,and activated the JNK/p38 MAPK pathway.Notably,treatment with NAC or SP600125 attenuated CSRNP1-induced MAPK activation and apoptosis.Conclusion:CSRNP1 is a novel prognostic biomarker and tumor suppressor in HCC.It exerts anti-tumor effects by inducing oxidative stress and activating the JNK/p38 MAPK pathway in a ROS-dependent manner.These findings suggest that CSRNP1 may serve as a potential therapeutic target in the management of HCC.
基金Supported by the Italian Ministry for Education,University and Research under the Programme“Dipartimenti di Eccellenza 2018-2022”Project,No.D15D18000410001Novo Nordisk“Gestione delle complicanze croniche del diabete:From bedside to bench?”,No.n1/2021.
文摘BACKGROUND Global longitudinal strain(GLS)of the left ventricular is a highly sensitive and reliable marker of systolic function and GLS outperforms ejection fraction(EF)in detecting preclinical left ventricular systolic dysfunction(LVSD).In patients with type 2 diabetes(DM2)albuminuria is a predictor of symptomatic heart failure,but data on the relationship between GLS and albuminuria are conflicting.AIM To explore the relationship between GLS and albuminuria in a contemporary cohort of DM2 patients.METHODS The study was performed on DM2 patients consecutively enrolled in the TESEO study.Patients with symptoms/signs of heart failure,EF<50%,coronary artery,other cardiac diseases,or non-adequate acoustic window for GLS assessment were excluded.We collected clinical data,screened for complications,and measured GLS by speckle-tracking echocardiography.Univariate and multiple linear regression analyses were performed to identify independent explanatory variables associated with GLS.Logistic regression analysis was used to assess whether albuminuria was independently associated with GLS-diagnosed(GLS>-18%)LVSD.RESULTS Patients(n=193,age:60.6±8.1,male:57%)had a short DM2 duration(3.8±4.9 years)and good metabolic control(glycated haemoglobin A1c:6.5%±1.0).Preclinical GLS-LVSD was present in 21.8%of the patients.GLS values were significantly higher in patients with albuminuria(-19.88±2.16 vs-18.29±2.99,P<0.001)and in multivariate analysis natural logarithm of albumin-creatinine ratio and uric acid were independent predictors of GLS.In logistic regression analysis,albuminuria was associated with a 6.01(95%confidence interval:1.874-19.286)increased odds ratio of GLS-LVSD,independent of age,sex,diastolic blood pressure,chronic kidney disease,EF,mitral annulus velocity lateral,uric acid,and treatments.CONCLUSION Albuminuria was independently associated with subclinical LVSD in our contemporary cohort of DM2 patients.
文摘Left ventricular diastolic dysfunction is frequently noticed in patients with chronic kidney disease.Echocardiography is used to determine the presence and severity of diastolic dysfunction.In left ventricular diastolic dysfunction the ventricular diastolic distensibility,filling or relaxation is abnormal;however,the left ventricular ejection fraction may be normal or decreased.In heart failure with preserved ejection fraction,the patients have symptomatic pulmonary congestion even though the systolic ejection fraction is more than 50%.This condition is commonly associated with ventricular diastolic dysfunction.Increased incidence of major adverse cardiovascular events has been reported in surgical patients having grade III diastolic dysfunction.Peri-operatively haemodynamic instability and fluid overload in this set of patients is known to generate pulmonary oedema.
文摘The feasibility and safety of total arterial coronary revascularization with 2 arterial conduits in patients with impaired left ventricular function was evaluated. Data were prospectively collected on all patients with multiple vessel disease and moderately or severely impaired left ventricular function, who underwent coronary surgery with the intention of total arterial revascularization with 2 conduits between March 1995 and August 2002. One hundred and seventy-nine patients were included in the study. Acute coronary insufficiency was present in 3 patients and 43 had unstable angina. Severe left ventricular impairment was present in 29 patients. There were 17 redo operations including 3 redo-redo procedures. Eighty-two percent of patients had a Y graft configuration from the left internal mammary artery （right internal mammary artery 40. 8 %, radial artery 33. 5 %, other 7.8 % ）. The perioperative mortality was 2. 2 %, myocardial infarction 1.7 % and stroke 0. 6 %. Total arterial revascularization in patients with ischaemic left ventricular dysfunction can be safely performed with 2 arterial conduits. The radial artery provides conduit length greater than the right internal mammary artery and allows full revascularization despite left ventricular dilatation.
文摘BACKGROUND Liver cirrhosis is a chronic hepatic disease which is associated with cardiovascular abnormalities.Hyperdynamic circulation in liver cirrhosis causes functional and structural cardiac alterations.The prevalence of left ventricle diastolic dysfunction(LVDD)in cirrhotic patients ranges from 25.7%to as high as 81.4%as reported in different studies.In several studies the severity of diastolic dysfunction(DD)correlated with a degree of liver failure and the rate of dysfunction was higher in patients with decompensated cirrhosis compared with compensated.Future directions of comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients.AIM To clarify the correlation between the severity of liver cirrhosis and left ventricle diastolic dysfunction in the existing literature.METHODS Through January and February of 2019 at Vilnius University we conducted a systematic review of the global existing literature on the prevalence of left ventricle diastolic dysfunction in patients with liver cirrhosis.We searched for articles in PubMed,Medline and Web of science databases.Articles were selected by using adequate inclusion and exclusion criteria.Our interest was the outcome of likely correlation between the severity of cirrhosis[evaluated by Child-Pugh classes,Model For End-Stage Liver Disease(MELD)scores]and left ventricle diastolic dysfunction[classified according to American Society of Echocardiography(ASE)guidelines(2009,2016)],as well as relative risk of dysfunction in cirrhotic patients.Subgroup analyses were performed to evaluate the ratio and grades of left ventricle diastolic dysfunction with respect to cirrhosis severity.RESULTS A total of 1149 articles and abstracts met the initial search criteria.Sixteen articles which met the predefined eligibility criteria were included in the final analysis.Overall,1067 patients(out of them 723 men)with liver cirrhosis were evaluated for left ventricle diastolic dysfunction.In our systemic analysis we have found that 51.2%of cirrhotic patients had left ventricle diastolic dysfunction diagnosed and the grade 1 was the most prevalent(59.2%,P<0.001)among them,the grade 3 had been rarely diagnosed-only 5.1%.The data about the prevalence of diastolic dysfunction in cirrhotic patients depending on Child-Pugh Classes was available from 5 studies(365 patients overall)and only in 1 research diastolic dysfunction was found being associated with severity of liver cirrhosis(P<0.005).We established that diastolic dysfunction was diagnosed in 44.6%of Child-Pugh A class patients,in 62%of Child B class and in 63.3%of Child C patients(P=0.028).The proportion of patients with higher diastolic dysfunction grades increases in more severe cirrhosis presentation(P<0.001).There was no difference between mean MELD scores in patients with and without diastolic dysfunction and in different diastolic dysfunction groups.In all studies diastolic dysfunction was more frequent in patients with ascites.CONCLUSION This systemic analysis suggests that left ventricle diastolic dysfunction is an attribute of liver cirrhosis which has not received sufficient attention from clinicians so far.Future suggestions of a comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients and give hint for better understanding of the left ventricle diastolic dysfunction pathogenesis in liver cirrhosis.
基金the China National Science&Technology Pillar Program(2011BAI11B01)the National Health and Family Planning Commission,China(No.201402002)the CAMS Innovation Fund for Medical Sciences(2017-I2M-1-004)。
文摘Background Heart failure(HF)is a leading cause of hospitalization and mortality for older chronic kidney disease(CKD)patients.However,the epidemiological data is scarce.We aimed to determine the prevalence of left ventricular(LV)dysfunction and HF,and to explore the risk factors for HF among those patients.Methods This is a cross-sectional analysis of the China Hypertension Survey conducted between October 2012 and December 2015.A total of 5,808 participants aged≥65 years were included in the analysis.Self-reported history of HF and any other cardiovascular diseases was acquired.2-D and Doppler echocardiography were used to assess LV dysfunction.CKD was defined as either estimated glomerular filtration rate(eGFR)<60 mL/min per 1.73 m2 or urinary albumin to creatinine ratio(ACR)≥30 mg/g.Results Among CKD patients aged≥65 years,the weighted prevalence of HF,heart failure with preserved ejection fraction(HFpEF),heart failure with mid-range ejection fraction(HFmrEF),and heart failure with reduced ejection fraction(HFrEF)was 4.8%,2.5%,0.8%,and 1.7%,respectively.The weighted prevalence of HF was 5.0%in patients with eGFR<60 mL/min per 1.73 m2,and was 5.9%in patients with ACR≥30 mg/g.The prevalence of LV systolic dysfunction was 3.1%,and while it was 8.9%for moderate/severe diastolic dysfunction.Multivariate analysis showed that smoking was significantly associated with the risk of HF.Furthermore,age,smoking,and residents in rural areas were significantly associated with a risk of LV diastolic dysfunction.Conclusions The prevalence of HF and LV dysfunction was high in older patients with CKD,suggesting that particular strategies will be required.
基金Supported by the University of Louisville-China Pediatric Research Exchange Program(Cai L,Tan Y,Huang J,and Keller B,no salary support)University of Louisville Executive Vice President for Research and Innovation Internal Grant(Huang J and Cai L)University of Louisville School of Medicine Basic Grant(Huang J and Cai L).
文摘BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.
