Heart failure(HF)with preserved ejection fraction(HFpEF)has exceeded HF with reduced ejection fraction(HFrEF),becoming the most common type of HF.Unlike HFrEF,HFpEF is primarily a chronic low-grade inflammatory proces...Heart failure(HF)with preserved ejection fraction(HFpEF)has exceeded HF with reduced ejection fraction(HFrEF),becoming the most common type of HF.Unlike HFrEF,HFpEF is primarily a chronic low-grade inflammatory process closely associated with metabolic disorders.The coexistence of HFpEF and metabolic dysfunction-associated steatotic liver disease(MASLD)presents significant clinical challenges due to shared metabolic pathophysiology and complex inter-play.Management strategies for HFpEF and MASLD remain challenging.Sodium-glucose cotransporter 2 inhibitors have shown benefits in managing both conditions.Additionally,glucagon-like peptide-1 receptor agonists are being actively investigated for their potential benefits,particularly in MASLD.A comprehensive,patient-centered approach that combines metabolic and cardiova-scular care is essential for improving outcomes in patients with HFpEF and MASLD,addressing the global metabolic health challenges.展开更多
Objectives To compare respiratory parameters of peripheral blood mononuclear cell mitochondria and iron metabolism indicators in patients with different NYHA functional classes of ischemic heart failure(HF).Methods Th...Objectives To compare respiratory parameters of peripheral blood mononuclear cell mitochondria and iron metabolism indicators in patients with different NYHA functional classes of ischemic heart failure(HF).Methods This single center, prospective, non-blinded study enrolled 20 patients with diagnosed chronic HF of ischemic genesis with reduced and mildly reduced left ventricle ejection fraction. The maximum oxygen consumption at the peak of the exercise test(VO2peak), iron metabolism parameters and respiratory activity of peripheral blood mononuclear cell mitochondria were assessed.Results Among the patients, a half of individuals were diagnosed with iron deficiency. Subgroups of patients with different HF severity did not significant differ in VO2peak(P=0.209), serum iron(P=0.468) and ferritin(P=0.235) levels. But there was a trend in increasing in these parameters with increasing NYHA HF functional class. Respiratory control coefficient(RC) in NADdependent and FAD-dependent mitochondrial oxidation were lower in patients with NYHA HF Ⅲ functional class compared to individuals with NYHA HF I functional class(P=0.028 and P=0.040, respectively). Serum iron(P=0.026), ferritin(P=0.045)levels, transferrin saturation(P=0.006) were negatively correlated with RC in NAD-dependent mitochondrial oxidation.Conclusions In aggravation of ischemic HF NYHA FC, there is a decrease in RC of PBMC mitochondria during the oxidation of NAD-dependent and FAD-dependent substrates. In the whole sample, patients with laboratory-confirmed iron deficiency accounted a half of the total number. Iron metabolism parameters had a paradoxical inverse relationship with the level of RC in PBMC mitochondria of patients with HF.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
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
BACKGROUND Anxiety,depression,and other negative emotions are common among patients with chronic renal failure(CRF).Analyzing the factors related to negative emotions is necessary to provide targeted nursing care.AIM ...BACKGROUND Anxiety,depression,and other negative emotions are common among patients with chronic renal failure(CRF).Analyzing the factors related to negative emotions is necessary to provide targeted nursing care.AIM To explore the correlations among life satisfaction,pleasure levels,and negative emotions in patients with CRF.METHODS One hundred patients with CRF who received therapy at the First Affiliated Hospital of Jinzhou Medical University between December 2022 and February 2025 were included.The Depression,Anxiety,and Stress Scale(DASS-21),Satisfaction with Life Scale(SWLS),and Temporal Experience of Pleasure Scale(TEPS)were used to evaluate negative emotions,life satisfaction,and pleasure level,respectively.Pearson’s correlation coefficient analyzed the correlation between life satisfaction,pleasure level,and negative emotions.Linear regression analysis identified the factors affecting negative emotions.RESULTS The average DASS-21 score among patients with CRF was 51.90±2.30,with subscale scores of 17.90±1.50 for depression,18.53±1.18 for anxiety,and 15.47±2.36 for stress,all significantly higher than the domestic norm(P<0.05).The average SWLS score was 22.17±4.90.Correlation analysis revealed a negative correlation between the SWLS and total DASS-21 scores(P<0.05),but not with the individual depression,anxiety,or stress dimensions.The average TEPS score was 67.80±8.34.TEPS scores were negatively correlated with the DASS-21 score and the stress dimension(P<0.05),but not with depression or anxiety.Linear regression analysis showed that TEPS scores significantly influenced DASS-21 scores(P<0.05).CONCLUSION Patients with CRF experience high levels of negative emotions,which are negatively correlated with life satisfaction and pleasure.Furthermore,pleasure level had an impact on negative emotions.展开更多
BACKGROUND Congenital hypothyroidism(CH)is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality.The clinical association of refractory lactic acidosis ...BACKGROUND Congenital hypothyroidism(CH)is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality.The clinical association of refractory lactic acidosis and heart failure has rarely been observed in cases of pediatric patients with CH pathology.Here,we explored the etiological relationship between CH,heart failure,and refractory lactic acidosis to reflect the importance of thyroid function screening in neonates with heart disease.CASE SUMMARY A 33-day-old extremely premature female infant presented with tachypnea,respiratory distress,recurrent infections,and abdominal distension postnatal.On admission to our facility,she had cardiomegaly,hepatomegaly,and lactic acidosis(revealed on blood gas analysis),with lactate progressively rising to 25 mmol/L.Chest radiographs showed pulmonary congestion,while echocardiography revealed cardiac enlargement,left ventricular wall thickening,and pericardial effusion.Initial management aimed at correcting acidosis and treating heart failure proved ineffective.After reassessment,thyroid function tests showed significantly decreased triiodothyronine,free triiodothyronine,thyroxine,and free thyroxine levels,with a significantly increased thyroidstimulating hormone level,confirming a CH diagnosis.Levothyroxine was administered,resulting in rapid correction of lactic acidosis and gradual improvement of thyroid function and systemic symptoms,culminating in full recovery and discharge.We also reviewed the relevant literature on thyroid and cardiac dysfunctions in order to explore their deeper association.CONCLUSION This case links CH-induced heart failure with refractory lactic acidosis,urging prompt thyroid screening in affected neonates to reduce mortality.展开更多
Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend ...Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend against illness,and maintain homeostasis)syndrome is considered a critical syndrome in traditional Chinese medicine(TCM)and is associated with poor prognosis in heart failure(HF).This study investigates the clinical,metabolic,and transcriptomic differences between heart failure patients with and without Qi deficiency syndrome.Methods:56 heart failure patients were evaluated using a Qi deficiency syndrome scale and divided into Qi deficiency syndrome(QD)and non-Qi deficiency(non-QD)groups based on the median score.Clinical characteristics,including baseline N-terminal pro-B-type natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),total diuretic use during hospitalization,and 90-day rehospitalization rates,were compared between the groups.Differentially expressed genes(DEGs)and differential metabolites were identified,followed by enrichment analyses and validation using qPCR and Western blot in AC16 cardiomyocytes.Results:QD patients exhibited significantly higher NT-proBNP levels,lower LVEF,and increased 90-day rehospitalization rates.Metabolomic profiling revealed lipid metabolism disruptions,notably in linoleic acid and phospholipid pathways.Transcriptomic analysis highlighted 17 DEGs,including CISD2,a critical mitochondrial regulator,which was downregulated in QD patients.Correlation analysis identified significant associations between DEGs(e.g.,CISD2,BPGM)and lipid metabolites such as PC(16:0/P-16:0).Functional knockdown of CISD2 in AC16 cells led to upregulation of lipid oxidation enzymes ALOX15 and CYP1A2,linking CISD2 dysfunction to lipid metabolic dysregulation.Conclusion:Qi deficiency is associated with more severe heart failure symptoms,worse prognosis,and distinct metabolic and transcriptomic profiles,particularly in lipid metabolism.CISD2 emerges as a potential therapeutic target,offering new avenues for integrating molecular insights with TCM approaches to optimize HF management.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
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
Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided ...Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided into the following groups: ischemia group and non-ischemia group, heart function Ⅰ-Ⅱ group and heart function Ⅲ-Ⅳ group, event group and non-event group, and 50 healthy volunteers were included in the control group. Realtime PCR was used to detect transcription factors T-bet and GATA-3 of Th1 and Th2; flow cytometry was applied to determine the ratio of Th17 and Treg cells; ELISA was employed to test cytokines IFN-γ, IL-4, IL-17 and IL-10 of peripheral blood Th1, Th2, Th17 and Treg cells, respectively; ultrasonic cardiogram was used to exploit to LVEF and LVEDd; and electrochemilu minescene immunoassay was used to examine plasma BNP. The differences of all indexes of all groups were analyzed and the correlation between CD4 T cells and clinical indexes was analyzed by Pearson correlation analysis. Results: As compared to the control group, the transcription factors T-bet and GATA-3 of Th1 and Th2, the ratio of cytokines Th17 and IFN-γ, cytokines IL-17, T-bet/GATA-3, IFN-γ/IL-4, Th17 cells/Treg cells, IL-17/IL-10 of the ischemia group and non-ischemia group, heart functionⅠ-Ⅱgroup and heart function Ⅲ-Ⅳ group, event group and non-event group were all increased significantly, while their transcription factor GATA-3 of Th2, cytokines IL4, Treg cells ratio, cytokines IL10 were decreased obviously. The differences showed statistical significance (P < 0.05). The increase or decrease of the partial CD4+ T cells of the ischemia group, heart function Ⅲ-Ⅳ group and event group was more distinctly. The results of Pearson correlation analysis showed that IFN-γ and IL-17 were significantly positively correlated with LVEDd and BNP, IL-4 and IL-10 were also significantly positively correlated with LVEF, but correlated negatively with BNP, and IL-17 was negatively correlative with LVEF. Conclusions: There was a correlation between CHF and the dysfunction of CD4+ T cells showing immune activation phenomenons of deviations from the Th1/Th2 balance towards Th1 and from the Th17/Treg balance towards Th17, which was also related to the types, severity and prognosis of the disease.展开更多
BACKGROUND Chronic heart failure(CHF)is a complex syndrome characterized by a progressive reduction of the left ventricular(LV)contractility,low exercise tolerance,and increased mortality and morbidity.Diastolic dysfu...BACKGROUND Chronic heart failure(CHF)is a complex syndrome characterized by a progressive reduction of the left ventricular(LV)contractility,low exercise tolerance,and increased mortality and morbidity.Diastolic dysfunction(DD)of the LV,is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases.Also,it is well estimated that exercise training induces several beneficial effects on patients with CHF.AIM To evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction(EF)in patients with CHF.METHODS Thirty-two stable patients with CHF(age:56±10 years,EF:32%±8%,88%men)participated in an exercise rehabilitation program.They were randomly assigned to aerobic exercise(AER)or combined aerobic and strength training(COM),based on age and peak oxygen uptake,as stratified randomization criteria.Before and after the program,they underwent a symptom-limited maximal cardiopulmonary exercise testing(CPET)and serial echocardiography evaluation to evaluate peak oxygen uptake(VO2peak),peak workload(Wpeak),DD grade,right ventricular systolic pressure(RVSP),and EF.RESULTS The whole cohort improved VO2peak,and Wpeak,as well as DD grade(P<0.05).Overall,9 patients(28.1%)improved DD grade,while 23(71.9%)remained at the same DD grade;this was a significant difference,considering DD grade at baseline(P<0.05).In addition,the whole cohort improved RVSP and EF(P<0.05).Not any between-group differences were observed in the variables assessed(P>0.05).CONCLUSION Exercise rehabilitation improves indices of diastolic and systolic dysfunction.Exercise protocol was not observed to affect outcomes.These results need to be further investigated in larger samples.展开更多
OBJECTIVE To assess the role of beta-blockers(BB)in patients with chronic kidney disease(CKD)aged≥75 years.METHODS AND RESULTS From January 2008 to July 2014,we included 390 consecutive patients≥75 years of age with...OBJECTIVE To assess the role of beta-blockers(BB)in patients with chronic kidney disease(CKD)aged≥75 years.METHODS AND RESULTS From January 2008 to July 2014,we included 390 consecutive patients≥75 years of age with ejection fraction≤35%and glomerular filtration rate(GFR)≤60 m L/min per 1.73 m^2.We analyzed the relationship between treatment with BB and mortality or cardiovascular events.The mean age of our population was 82.6±4.1 years.Mean ejection fraction was 27.9%±6.5%.GFR was 60-45 m L/min per 1.73 m^2 in 50.3%of patients,45-30 m L/min per 1.73 m^2 in 37.4%,and<30 m L/min per 1.73 m^2 in 12.3%.At the conclusion of follow-up,67.4%of patients were receiving BB.The median follow-up was28.04(IR:19.41-36.67)months.During the study period,211 patients(54.1%)died and 257(65.9%)had a major cardiovascular event(death or hospitalization for heart failure).BB use was significantly associated with a reduced risk of death(HR=0.51,95%CI:0.35-0.74;P<0.001).Patients receiving BB consistently showed a reduced risk of death across the different stages of CKD:stage IIIa(GFR=30-45 m L/min per 1.73 m^2;HR=0.47,95%CI:0.26-0.86,P<0.0001),stage IIIb(GFR 30-45 m L/min per 1.73 m^2;HR=0.55,95%CI:0.26-1.06,P=0.007),and stages IV and V(GFR<30 m L/min per 1.73 m~2;HR=0.29,95%CI:0.11-0.76;P=0.047).CONCLUSIONS The use of BB in elderly patients with HFr EF and renal impairment was associated with a better prognosis.Use of BB should be encouraged when possible.展开更多
BACKGROUND:Acute liver failure(ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders,the accumulation of toxic substances and continuous release and accumulation of a large ...BACKGROUND:Acute liver failure(ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders,the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artif icial liver treatments for patients with acute liver failure(ALF) complicated by multiple organ dysfunction syndrome(MODS).METHODS:Thirty-one patients with mid- or late-stage liver failure complicated by MODS(score 4) were randomly divided into three treatment groups:plasmapheresis(PE) combined with hemoperfusion(HP) and continuous venovenous hemodiafiltration(CVVHDF),PE+CVVHDF,and HP+CVVHDF,respectively. Heart rate(HR) before and after treatment,mean arterial pressure(MAP),respiratory index(PaO2/FiO2),hepatic function,platelet count,and blood coagulation were determined.RESULTS:Signifi cant improvement was observed in HR,MAP,PaO2/FiO2,total bilirubin(TBIL) and alanine aminotransferase(ALT) levels after treatment(P<0.05). TBIL and ALT decreased more signifi cantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups(P<0.01). Prothrombin time(PT) and albumin were signifi cantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups(P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups(P<0.05). The survival rate of the patients was 58.1%(18/31),viral survival rate 36.4%(4/11),and non-viral survival rate 70%(14/20).CONCLUSION:Liver function was relatively improved after treatment,but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites,especially bilirubin. The survival rate was signifi cantly higher in the patients with non-viral liver failure than in those with viral liver failure.展开更多
The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial d...The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Interestingly, mitochondrial dysfunction has been observed to occur during the early onset of several neuropathological events associated to neurodegenerative diseases. The master regulator of mitochondrial quality control and energetic metabolism is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α). Additionally, it has been observed that PGC-1α appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1α downregulation in different brain areas(hippocampus, substantia nigra, cortex, striatum and spinal cord) that occurs in function of neurological damage including oxidative stress, neuronal loss, and motor disorders has been seen in several animal and cellular models of neurodegenerative diseases. Current evidence indicates that PGC-1α upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1α deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1α isoforms in the central nervous system that appear to exert a key role in the age of onset of neurodegenerative diseases and have a neuroprotective function in the central nervous system, thus opening a new molecular strategy for treatment of neurodegenerative diseases. The purpose of this review is to provide an up-to-date overview of the PGC-1α role in the physiopathology of neurodegenerative diseases, as well as establish the importance of PGC-1α function in synaptic transmission and neuronal survival.展开更多
This review highlights some established and some more contemporary mechanisms responsible for heart failure(HF)-induced skeletal muscle wasting and weakness.We first describe the effects of HF on the relationship betw...This review highlights some established and some more contemporary mechanisms responsible for heart failure(HF)-induced skeletal muscle wasting and weakness.We first describe the effects of HF on the relationship between protein synthesis and degradation rates,which determine muscle mass,the involvement of the satellite cells for continual muscle regeneration,and changes in myofiber calcium homeostasis linked to contractile dysfunction.We then highlight key mechanistic effects of both aerobic and resistance exercise training on skeletal muscle in HF and outline its application as a beneficial treatment.Overall,HF causes multiple impairments related to autophagy,anabolic-catabolic signaling,satellite cell proliferation,and calcium homeostasis,which together promote fiber atrophy,contractile dysfunction,and impaired regeneration.Although both wasting and weakness are partly rescued by aerobic and resistance exercise training in HF,the effects of satellite cell dynamics remain poorly explored.展开更多
Heart failure(HF)is a major global public health concern,and one of the less commonly known risk factors for HF development is metabolic dysfunction-associated steatotic liver disease(MASLD),as they share a similar pa...Heart failure(HF)is a major global public health concern,and one of the less commonly known risk factors for HF development is metabolic dysfunction-associated steatotic liver disease(MASLD),as they share a similar pathophysio-logical background.In this article,we evaluated a recently published review article by Arriola-Montenegro et al.This article briefly summarizes the common pathophysiology of HF and MASLD development and evaluates the available therapeutic options to treat both conditions.Clinical practice guidelines highlight the importance of initiating and titrating guideline-directed medication therapy(GDMT)for patients with HF with reduced ejection fraction.GDMT is comprised of the four pillars currently proposed in most clinical practice guidelines,namely angiotensin-converting enzyme inhibitors(ACEIs),angiotensin receptor blockers(ARBs),angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocor-ticoid receptor antagonists,and sodium-glucose co-transporter 2 inhibitors(SGLT-2i).Given the similarity of pathophysiology and risk factors,recent studies for GDMT regarding ACEIs,ARBs,mineralocorticoid receptor antagonists,and SGLT-2i have shown beneficial effects on MASLD.Nonetheless,other medications for both conditions and novel therapies require more robust data and well-designed clinical studies to demonstrate their efficacies in both conditions.展开更多
Background and Objective Diastolic dysfunction of the left ventricle is a mechanical abnormality diagnosed primarily by echocardiogram, and can be distinguished into three separate degrees based on the severity of red...Background and Objective Diastolic dysfunction of the left ventricle is a mechanical abnormality diagnosed primarily by echocardiogram, and can be distinguished into three separate degrees based on the severity of reduction in passive compliance and active myocardial relaxation. Methods A literature search was performed for basic science studies, clinical studies and major practice guidelines on the subject of diastolic dysfunction and diastolic heart failure. Important findings were analyzed and correlated with regard to clinical relevance. Results Left ventricular diastolic dysfunction appears to compromise exercise tolerance and is believed to contribute to the pathophysiology in patients with diastolic heart failure. In the clinical setting, however, oftentimes no clear distinction is made between echocardiographically diagnosed diastolic dysfunction and diastolic heart failure, and adequate treatment recommendations are sparse and aimed to prevent worsening and progression of clinical symptoms. To date, there is a lack of high powered trials assessing the possible progression rate from echocardiographically diagnosed diastolic dysfunction to the clinical diagnosis of diastolic heart failure. Furthermore, there are no solid indices to assess the degree of severity of diastolic dysfunction or its progression. Pure right ventricular diastolic dysfunction appears to be even less understood and under-recognized, although it may play a role in the development of both right and left heart failure. Currently there are few but interesting data on the possible interaction between ventricles with diastolic dysfunction and the overall affect on the development of heart failure. Conclusions The timeline and progression of diastolic dysfunction to diastolic heart failure have not been well established and warrant further investigation.展开更多
BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mecha...BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines.CONCLUSION The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling,leading to advanced HBV-ACLF.These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.展开更多
基金Supported by Wenzhou Science Technology Bureau Foundation,No.2022Y0726.
文摘Heart failure(HF)with preserved ejection fraction(HFpEF)has exceeded HF with reduced ejection fraction(HFrEF),becoming the most common type of HF.Unlike HFrEF,HFpEF is primarily a chronic low-grade inflammatory process closely associated with metabolic disorders.The coexistence of HFpEF and metabolic dysfunction-associated steatotic liver disease(MASLD)presents significant clinical challenges due to shared metabolic pathophysiology and complex inter-play.Management strategies for HFpEF and MASLD remain challenging.Sodium-glucose cotransporter 2 inhibitors have shown benefits in managing both conditions.Additionally,glucagon-like peptide-1 receptor agonists are being actively investigated for their potential benefits,particularly in MASLD.A comprehensive,patient-centered approach that combines metabolic and cardiova-scular care is essential for improving outcomes in patients with HFpEF and MASLD,addressing the global metabolic health challenges.
基金supported by Russian Science Foundation,RSF 23-75-00009(part of the study corresponding to finding 1)Part of the study corresponding to finding 2 was carried out within the state assignment,FSR No.:122020300045-5(03.02.2022).
文摘Objectives To compare respiratory parameters of peripheral blood mononuclear cell mitochondria and iron metabolism indicators in patients with different NYHA functional classes of ischemic heart failure(HF).Methods This single center, prospective, non-blinded study enrolled 20 patients with diagnosed chronic HF of ischemic genesis with reduced and mildly reduced left ventricle ejection fraction. The maximum oxygen consumption at the peak of the exercise test(VO2peak), iron metabolism parameters and respiratory activity of peripheral blood mononuclear cell mitochondria were assessed.Results Among the patients, a half of individuals were diagnosed with iron deficiency. Subgroups of patients with different HF severity did not significant differ in VO2peak(P=0.209), serum iron(P=0.468) and ferritin(P=0.235) levels. But there was a trend in increasing in these parameters with increasing NYHA HF functional class. Respiratory control coefficient(RC) in NADdependent and FAD-dependent mitochondrial oxidation were lower in patients with NYHA HF Ⅲ functional class compared to individuals with NYHA HF I functional class(P=0.028 and P=0.040, respectively). Serum iron(P=0.026), ferritin(P=0.045)levels, transferrin saturation(P=0.006) were negatively correlated with RC in NAD-dependent mitochondrial oxidation.Conclusions In aggravation of ischemic HF NYHA FC, there is a decrease in RC of PBMC mitochondria during the oxidation of NAD-dependent and FAD-dependent substrates. In the whole sample, patients with laboratory-confirmed iron deficiency accounted a half of the total number. Iron metabolism parameters had a paradoxical inverse relationship with the level of RC in PBMC mitochondria of patients with HF.
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.
文摘BACKGROUND Anxiety,depression,and other negative emotions are common among patients with chronic renal failure(CRF).Analyzing the factors related to negative emotions is necessary to provide targeted nursing care.AIM To explore the correlations among life satisfaction,pleasure levels,and negative emotions in patients with CRF.METHODS One hundred patients with CRF who received therapy at the First Affiliated Hospital of Jinzhou Medical University between December 2022 and February 2025 were included.The Depression,Anxiety,and Stress Scale(DASS-21),Satisfaction with Life Scale(SWLS),and Temporal Experience of Pleasure Scale(TEPS)were used to evaluate negative emotions,life satisfaction,and pleasure level,respectively.Pearson’s correlation coefficient analyzed the correlation between life satisfaction,pleasure level,and negative emotions.Linear regression analysis identified the factors affecting negative emotions.RESULTS The average DASS-21 score among patients with CRF was 51.90±2.30,with subscale scores of 17.90±1.50 for depression,18.53±1.18 for anxiety,and 15.47±2.36 for stress,all significantly higher than the domestic norm(P<0.05).The average SWLS score was 22.17±4.90.Correlation analysis revealed a negative correlation between the SWLS and total DASS-21 scores(P<0.05),but not with the individual depression,anxiety,or stress dimensions.The average TEPS score was 67.80±8.34.TEPS scores were negatively correlated with the DASS-21 score and the stress dimension(P<0.05),but not with depression or anxiety.Linear regression analysis showed that TEPS scores significantly influenced DASS-21 scores(P<0.05).CONCLUSION Patients with CRF experience high levels of negative emotions,which are negatively correlated with life satisfaction and pleasure.Furthermore,pleasure level had an impact on negative emotions.
文摘BACKGROUND Congenital hypothyroidism(CH)is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality.The clinical association of refractory lactic acidosis and heart failure has rarely been observed in cases of pediatric patients with CH pathology.Here,we explored the etiological relationship between CH,heart failure,and refractory lactic acidosis to reflect the importance of thyroid function screening in neonates with heart disease.CASE SUMMARY A 33-day-old extremely premature female infant presented with tachypnea,respiratory distress,recurrent infections,and abdominal distension postnatal.On admission to our facility,she had cardiomegaly,hepatomegaly,and lactic acidosis(revealed on blood gas analysis),with lactate progressively rising to 25 mmol/L.Chest radiographs showed pulmonary congestion,while echocardiography revealed cardiac enlargement,left ventricular wall thickening,and pericardial effusion.Initial management aimed at correcting acidosis and treating heart failure proved ineffective.After reassessment,thyroid function tests showed significantly decreased triiodothyronine,free triiodothyronine,thyroxine,and free thyroxine levels,with a significantly increased thyroidstimulating hormone level,confirming a CH diagnosis.Levothyroxine was administered,resulting in rapid correction of lactic acidosis and gradual improvement of thyroid function and systemic symptoms,culminating in full recovery and discharge.We also reviewed the relevant literature on thyroid and cardiac dysfunctions in order to explore their deeper association.CONCLUSION This case links CH-induced heart failure with refractory lactic acidosis,urging prompt thyroid screening in affected neonates to reduce mortality.
基金supported by the Sanming Project of Medicine in Shenzhen[SZZYSM202206001]National Natural Science Foundation of China[82004320 and 82374383]+3 种基金Natural Science Foundation of Guangdong Province of China[2022A1515011710 and 2022A1515010679]Shenzhen Science and Technology Innovation Committee[JCYJ20220530141407017 and JCYJ20240813153619026]2024 High-quality Development Research Project of Shenzhen Bao’an Public Hospital[YNXM2024078]and Shenzhen Bao’an Chinese Medicine Hospital Research Program[BAZYY20220702].
文摘Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend against illness,and maintain homeostasis)syndrome is considered a critical syndrome in traditional Chinese medicine(TCM)and is associated with poor prognosis in heart failure(HF).This study investigates the clinical,metabolic,and transcriptomic differences between heart failure patients with and without Qi deficiency syndrome.Methods:56 heart failure patients were evaluated using a Qi deficiency syndrome scale and divided into Qi deficiency syndrome(QD)and non-Qi deficiency(non-QD)groups based on the median score.Clinical characteristics,including baseline N-terminal pro-B-type natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),total diuretic use during hospitalization,and 90-day rehospitalization rates,were compared between the groups.Differentially expressed genes(DEGs)and differential metabolites were identified,followed by enrichment analyses and validation using qPCR and Western blot in AC16 cardiomyocytes.Results:QD patients exhibited significantly higher NT-proBNP levels,lower LVEF,and increased 90-day rehospitalization rates.Metabolomic profiling revealed lipid metabolism disruptions,notably in linoleic acid and phospholipid pathways.Transcriptomic analysis highlighted 17 DEGs,including CISD2,a critical mitochondrial regulator,which was downregulated in QD patients.Correlation analysis identified significant associations between DEGs(e.g.,CISD2,BPGM)and lipid metabolites such as PC(16:0/P-16:0).Functional knockdown of CISD2 in AC16 cells led to upregulation of lipid oxidation enzymes ALOX15 and CYP1A2,linking CISD2 dysfunction to lipid metabolic dysregulation.Conclusion:Qi deficiency is associated with more severe heart failure symptoms,worse prognosis,and distinct metabolic and transcriptomic profiles,particularly in lipid metabolism.CISD2 emerges as a potential therapeutic target,offering new avenues for integrating molecular insights with TCM approaches to optimize HF management.
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.
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 Brainstorm Project of Guizhou Science and Technology Office (Grant No.SY 20133016)Guiyang Science and Technology Planning Project (Grand No.20151001)
文摘Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided into the following groups: ischemia group and non-ischemia group, heart function Ⅰ-Ⅱ group and heart function Ⅲ-Ⅳ group, event group and non-event group, and 50 healthy volunteers were included in the control group. Realtime PCR was used to detect transcription factors T-bet and GATA-3 of Th1 and Th2; flow cytometry was applied to determine the ratio of Th17 and Treg cells; ELISA was employed to test cytokines IFN-γ, IL-4, IL-17 and IL-10 of peripheral blood Th1, Th2, Th17 and Treg cells, respectively; ultrasonic cardiogram was used to exploit to LVEF and LVEDd; and electrochemilu minescene immunoassay was used to examine plasma BNP. The differences of all indexes of all groups were analyzed and the correlation between CD4 T cells and clinical indexes was analyzed by Pearson correlation analysis. Results: As compared to the control group, the transcription factors T-bet and GATA-3 of Th1 and Th2, the ratio of cytokines Th17 and IFN-γ, cytokines IL-17, T-bet/GATA-3, IFN-γ/IL-4, Th17 cells/Treg cells, IL-17/IL-10 of the ischemia group and non-ischemia group, heart functionⅠ-Ⅱgroup and heart function Ⅲ-Ⅳ group, event group and non-event group were all increased significantly, while their transcription factor GATA-3 of Th2, cytokines IL4, Treg cells ratio, cytokines IL10 were decreased obviously. The differences showed statistical significance (P < 0.05). The increase or decrease of the partial CD4+ T cells of the ischemia group, heart function Ⅲ-Ⅳ group and event group was more distinctly. The results of Pearson correlation analysis showed that IFN-γ and IL-17 were significantly positively correlated with LVEDd and BNP, IL-4 and IL-10 were also significantly positively correlated with LVEF, but correlated negatively with BNP, and IL-17 was negatively correlative with LVEF. Conclusions: There was a correlation between CHF and the dysfunction of CD4+ T cells showing immune activation phenomenons of deviations from the Th1/Th2 balance towards Th1 and from the Th17/Treg balance towards Th17, which was also related to the types, severity and prognosis of the disease.
文摘BACKGROUND Chronic heart failure(CHF)is a complex syndrome characterized by a progressive reduction of the left ventricular(LV)contractility,low exercise tolerance,and increased mortality and morbidity.Diastolic dysfunction(DD)of the LV,is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases.Also,it is well estimated that exercise training induces several beneficial effects on patients with CHF.AIM To evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction(EF)in patients with CHF.METHODS Thirty-two stable patients with CHF(age:56±10 years,EF:32%±8%,88%men)participated in an exercise rehabilitation program.They were randomly assigned to aerobic exercise(AER)or combined aerobic and strength training(COM),based on age and peak oxygen uptake,as stratified randomization criteria.Before and after the program,they underwent a symptom-limited maximal cardiopulmonary exercise testing(CPET)and serial echocardiography evaluation to evaluate peak oxygen uptake(VO2peak),peak workload(Wpeak),DD grade,right ventricular systolic pressure(RVSP),and EF.RESULTS The whole cohort improved VO2peak,and Wpeak,as well as DD grade(P<0.05).Overall,9 patients(28.1%)improved DD grade,while 23(71.9%)remained at the same DD grade;this was a significant difference,considering DD grade at baseline(P<0.05).In addition,the whole cohort improved RVSP and EF(P<0.05).Not any between-group differences were observed in the variables assessed(P>0.05).CONCLUSION Exercise rehabilitation improves indices of diastolic and systolic dysfunction.Exercise protocol was not observed to affect outcomes.These results need to be further investigated in larger samples.
文摘OBJECTIVE To assess the role of beta-blockers(BB)in patients with chronic kidney disease(CKD)aged≥75 years.METHODS AND RESULTS From January 2008 to July 2014,we included 390 consecutive patients≥75 years of age with ejection fraction≤35%and glomerular filtration rate(GFR)≤60 m L/min per 1.73 m^2.We analyzed the relationship between treatment with BB and mortality or cardiovascular events.The mean age of our population was 82.6±4.1 years.Mean ejection fraction was 27.9%±6.5%.GFR was 60-45 m L/min per 1.73 m^2 in 50.3%of patients,45-30 m L/min per 1.73 m^2 in 37.4%,and<30 m L/min per 1.73 m^2 in 12.3%.At the conclusion of follow-up,67.4%of patients were receiving BB.The median follow-up was28.04(IR:19.41-36.67)months.During the study period,211 patients(54.1%)died and 257(65.9%)had a major cardiovascular event(death or hospitalization for heart failure).BB use was significantly associated with a reduced risk of death(HR=0.51,95%CI:0.35-0.74;P<0.001).Patients receiving BB consistently showed a reduced risk of death across the different stages of CKD:stage IIIa(GFR=30-45 m L/min per 1.73 m^2;HR=0.47,95%CI:0.26-0.86,P<0.0001),stage IIIb(GFR 30-45 m L/min per 1.73 m^2;HR=0.55,95%CI:0.26-1.06,P=0.007),and stages IV and V(GFR<30 m L/min per 1.73 m~2;HR=0.29,95%CI:0.11-0.76;P=0.047).CONCLUSIONS The use of BB in elderly patients with HFr EF and renal impairment was associated with a better prognosis.Use of BB should be encouraged when possible.
基金supported by a grant from Xuzhou Municipal,China
文摘BACKGROUND:Acute liver failure(ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders,the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artif icial liver treatments for patients with acute liver failure(ALF) complicated by multiple organ dysfunction syndrome(MODS).METHODS:Thirty-one patients with mid- or late-stage liver failure complicated by MODS(score 4) were randomly divided into three treatment groups:plasmapheresis(PE) combined with hemoperfusion(HP) and continuous venovenous hemodiafiltration(CVVHDF),PE+CVVHDF,and HP+CVVHDF,respectively. Heart rate(HR) before and after treatment,mean arterial pressure(MAP),respiratory index(PaO2/FiO2),hepatic function,platelet count,and blood coagulation were determined.RESULTS:Signifi cant improvement was observed in HR,MAP,PaO2/FiO2,total bilirubin(TBIL) and alanine aminotransferase(ALT) levels after treatment(P<0.05). TBIL and ALT decreased more signifi cantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups(P<0.01). Prothrombin time(PT) and albumin were signifi cantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups(P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups(P<0.05). The survival rate of the patients was 58.1%(18/31),viral survival rate 36.4%(4/11),and non-viral survival rate 70%(14/20).CONCLUSION:Liver function was relatively improved after treatment,but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites,especially bilirubin. The survival rate was signifi cantly higher in the patients with non-viral liver failure than in those with viral liver failure.
基金supported by Fondecyt 1200908(to JF)the Conicyt 21141247(to JDP)。
文摘The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Interestingly, mitochondrial dysfunction has been observed to occur during the early onset of several neuropathological events associated to neurodegenerative diseases. The master regulator of mitochondrial quality control and energetic metabolism is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α). Additionally, it has been observed that PGC-1α appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1α downregulation in different brain areas(hippocampus, substantia nigra, cortex, striatum and spinal cord) that occurs in function of neurological damage including oxidative stress, neuronal loss, and motor disorders has been seen in several animal and cellular models of neurodegenerative diseases. Current evidence indicates that PGC-1α upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1α deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1α isoforms in the central nervous system that appear to exert a key role in the age of onset of neurodegenerative diseases and have a neuroprotective function in the central nervous system, thus opening a new molecular strategy for treatment of neurodegenerative diseases. The purpose of this review is to provide an up-to-date overview of the PGC-1α role in the physiopathology of neurodegenerative diseases, as well as establish the importance of PGC-1α function in synaptic transmission and neuronal survival.
基金supported by Heart Research UK(Grant number 119191)British Heart Foundation(Grant number 124055)。
文摘This review highlights some established and some more contemporary mechanisms responsible for heart failure(HF)-induced skeletal muscle wasting and weakness.We first describe the effects of HF on the relationship between protein synthesis and degradation rates,which determine muscle mass,the involvement of the satellite cells for continual muscle regeneration,and changes in myofiber calcium homeostasis linked to contractile dysfunction.We then highlight key mechanistic effects of both aerobic and resistance exercise training on skeletal muscle in HF and outline its application as a beneficial treatment.Overall,HF causes multiple impairments related to autophagy,anabolic-catabolic signaling,satellite cell proliferation,and calcium homeostasis,which together promote fiber atrophy,contractile dysfunction,and impaired regeneration.Although both wasting and weakness are partly rescued by aerobic and resistance exercise training in HF,the effects of satellite cell dynamics remain poorly explored.
文摘Heart failure(HF)is a major global public health concern,and one of the less commonly known risk factors for HF development is metabolic dysfunction-associated steatotic liver disease(MASLD),as they share a similar pathophysio-logical background.In this article,we evaluated a recently published review article by Arriola-Montenegro et al.This article briefly summarizes the common pathophysiology of HF and MASLD development and evaluates the available therapeutic options to treat both conditions.Clinical practice guidelines highlight the importance of initiating and titrating guideline-directed medication therapy(GDMT)for patients with HF with reduced ejection fraction.GDMT is comprised of the four pillars currently proposed in most clinical practice guidelines,namely angiotensin-converting enzyme inhibitors(ACEIs),angiotensin receptor blockers(ARBs),angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocor-ticoid receptor antagonists,and sodium-glucose co-transporter 2 inhibitors(SGLT-2i).Given the similarity of pathophysiology and risk factors,recent studies for GDMT regarding ACEIs,ARBs,mineralocorticoid receptor antagonists,and SGLT-2i have shown beneficial effects on MASLD.Nonetheless,other medications for both conditions and novel therapies require more robust data and well-designed clinical studies to demonstrate their efficacies in both conditions.
文摘Background and Objective Diastolic dysfunction of the left ventricle is a mechanical abnormality diagnosed primarily by echocardiogram, and can be distinguished into three separate degrees based on the severity of reduction in passive compliance and active myocardial relaxation. Methods A literature search was performed for basic science studies, clinical studies and major practice guidelines on the subject of diastolic dysfunction and diastolic heart failure. Important findings were analyzed and correlated with regard to clinical relevance. Results Left ventricular diastolic dysfunction appears to compromise exercise tolerance and is believed to contribute to the pathophysiology in patients with diastolic heart failure. In the clinical setting, however, oftentimes no clear distinction is made between echocardiographically diagnosed diastolic dysfunction and diastolic heart failure, and adequate treatment recommendations are sparse and aimed to prevent worsening and progression of clinical symptoms. To date, there is a lack of high powered trials assessing the possible progression rate from echocardiographically diagnosed diastolic dysfunction to the clinical diagnosis of diastolic heart failure. Furthermore, there are no solid indices to assess the degree of severity of diastolic dysfunction or its progression. Pure right ventricular diastolic dysfunction appears to be even less understood and under-recognized, although it may play a role in the development of both right and left heart failure. Currently there are few but interesting data on the possible interaction between ventricles with diastolic dysfunction and the overall affect on the development of heart failure. Conclusions The timeline and progression of diastolic dysfunction to diastolic heart failure have not been well established and warrant further investigation.
基金the Domestic First-class Construction Disciplines of the Hunan University of Chinese MedicinePostgraduate Research Innovation Program of Hunan Province,No.CX20220771Clinical MedTech Innovation Project of Hunan Province,No.2021SK51415.
文摘BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines.CONCLUSION The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling,leading to advanced HBV-ACLF.These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.
