The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cel...The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.展开更多
Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains uncle...Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.展开更多
When mammals are exposed to cold,their metabolism undergoes substantial changes.The liver plays a central role in maintaining energy homeostasis by shifting from glucose metabolism to lipid catabolism.A recent study b...When mammals are exposed to cold,their metabolism undergoes substantial changes.The liver plays a central role in maintaining energy homeostasis by shifting from glucose metabolism to lipid catabolism.A recent study by Davidson et al.^([1]),published in Cell Metabolism,highlights a novel mechanism involving lysosomal lipid remodeling during cold adaptation.Specifically,the study reveals that cold exposure elevates hepatic levels of Bis(Monoacylglycerol)Phosphate(BMP)lipids,which are regulated by Transcription Factor EB(TFEB)and Phospholipase A2 group XV(PLA2G15).展开更多
The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced m...The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced myocardial remodeling by activating the PI3K/AKT1 pathway.The cardiac function of mice was evaluated by echocardiography,revealing that MgIG could improve left ventricular function.Pathological staining analysis showed that MgIG could reduce the degree of myocardial injury caused by ISO.Serum data detected by ELISA demonstrated that MgIG could decrease the levels of CK-MB,MDA,and LDH while increasing the activity of GSH-Px.Western blotting analysis revealed that protein expression levels of Collagen I,BNP,Bax,cleaved caspase-3,p-PI3K,and p-AKT1 were decreased,whereas the protein expressions of Bcl-2,COX2,and SOD1 were increased upon MgIG treatment.However,the activation of the PI3K pathway reversed the cardioprotective effects of MgIG,as evidenced by the addition of PI3K activators.Taken together,our comprehensive results suggested that MgIG could improve ISO-induced myocardial remodeling,potentially through its mechanism of inhibiting the PI3K/AKT1 pathway to regulate apoptosis and oxidative stress.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyl...Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyladenosine(m^(6)A)modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes.However,whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown.We found that expression of methyltransferase 14 protein(METTL14)in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels.Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury.Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction,we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner,thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration.Finally,we administered syringin,a stabilizer of METTL14,using molecular docking.Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14.Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)is characterized by hepatic steatosis and may progress to severe steatohepatitis with associated fibrosis[1].There is a notable lack of effective and widely a...Metabolic dysfunction-associated fatty liver disease(MAFLD)is characterized by hepatic steatosis and may progress to severe steatohepatitis with associated fibrosis[1].There is a notable lack of effective and widely accepted pharmacological interventions for MAFLD.The fruits of Forsythia suspensa has been used in the treatment of cholestatic liver injury,hepatitis,and liver fibrosis.However,the effective constituent remains unknown.展开更多
Astrocytes and microglia are emerging key regulators of activity-dependent synapse remodeling that engulf and remove synapses in response to changes in neural activity.Yet,the degree to which these cells communicate t...Astrocytes and microglia are emerging key regulators of activity-dependent synapse remodeling that engulf and remove synapses in response to changes in neural activity.Yet,the degree to which these cells communicate to coordinate this process remains an open question.Here,we use whisker removal in postnatal mice to induce activity-dependent synapse removal in the barrel cortex.We show that astrocytes do not engulf synapses in this paradigm.Instead,astrocytes reduce contact with synapses prior to microglia-mediated synapse engulfment.展开更多
Mechanical loading constitutes a fundamental determinant in the process of bone remodeling.This modeling encompasses the incorporation of mechanical stimuli,the involvement of cellular and molecular constituents,as we...Mechanical loading constitutes a fundamental determinant in the process of bone remodeling.This modeling encompasses the incorporation of mechanical stimuli,the involvement of cellular and molecular constituents,as well as the utilization of sophisticated computational methodologies.Such an approach is imperative for forecasting bone behaviour across varying environmental conditions.In the present study,key findings from bone mechanobiology are reviewed,along with the possibility that Functionally Graded Materials(FGM)enhances osseointegration and lowers the stress-shielding effect during bone remodeling and compared to titanium,FGM improves periprosthetic bone remodeling.To summarise some of the most important findings from computational models of bone mechanobiology,explaining how modifications to the mechanical environment affect implant design,growth of bone,and bone response.The impact that changes related to the mechanical environment have on bone response is examined using computational models and methods such as surface microtopography to determine how an implant’s bone density has increased over time.This review focuses on the refinement of advanced simulation frameworks and their synergy with imaging technologies to strengthen model validation,ultimately resulting in better clinical outcomes in the context of bone health treatments.展开更多
The insect fat body is comparable to the liver and adipose tissue in vertebrates,and plays a pivotal role in energy metabolism,nutrient storage,and reproduction.During metamorphosis,the fat body is disassembled via pr...The insect fat body is comparable to the liver and adipose tissue in vertebrates,and plays a pivotal role in energy metabolism,nutrient storage,and reproduction.During metamorphosis,the fat body is disassembled via programmed cell death and cell dissociation.After adult eclosion,the fat body is reconstructed either by repopulation from the remaining juvenile fat body cells or by differentiation from adult progenitor cells.This reconstruction is a prerequisite for initiating the extensive synthesis of vitellogenin(Vg),which is necessary for the maturation of eggs.Despite its significance,the underlying mechanisms of this reconstruction remain inadequately understood.Transcriptome analysis of the fat bodies from migratory locusts at 0-5 days post adult emergence revealed 79 genes associated with chromatin remodeling.Weighted gene co-expression network analysis indicated a positive correlation between chromatin remodeling and fat body reconstitution.Protein-protein interaction analysis revealed that brahma,which encodes the catalytic subunit of the SWI/SNF chromatin remodeling complex,is crucial for post-adult-eclosion fat body development.qRT-PCR analysis demonstrated that the levels of brahma mRNA in the fat body are progressively increased during the previtellogenic stage,then reach the peak and remain elevated in the vitellogenic phase.Furthermore,brahma is expressed in response to gonadotropic juvenile hormone(JH).Knockdown of brahma led to a marked reduction in Vg expression within the fat body,along with arrested ovarian growth.These findings shed light on the involvement of brahmamediated chromatin remodeling in JH-stimulated fat body reconstruction and reproduction of adult female locusts.展开更多
BACKGROUND Chronic heart failure(CHF)is a severe cardiovascular disease that significantly threatens human health.Depression,a common comorbidity,may substantially impact cardiac structure and function.However,the exa...BACKGROUND Chronic heart failure(CHF)is a severe cardiovascular disease that significantly threatens human health.Depression,a common comorbidity,may substantially impact cardiac structure and function.However,the exact relationship between depression and cardiac remodeling and left ventricular functional changes remains incompletely understood.This study sets out to explore,with a clinically grounded perspective,how depressive states may subtly or profoundly influence the trajectory of cardiac remodeling and the functional dynamics of the left ventricle in individuals grappling with CHF.Beyond mere observation,it also aims to untangle the underlying physiological or neurohormonal pathways that might bridge emotional distress and cardiac dysfunction.AIM To delve into how depressive symptoms might shape the progression of cardiac remodeling and impair left ventricular function among individuals living with CHF.Particular attention is given to the role of inflammatory signaling and disruptions in neuroendocrine balance as possible mediating factors.By examining these intertwined physiological and psychological processes,the study seeks to shed light on the reciprocal link between emotional distress and CHF,offering insights that may inform more precise,mechanism-based treatment strategies.METHODS In this retrospective clinical trial,248 patients diagnosed with CHF were analyzed in the tertiary treatment center between January 2018 and December 2022.According to Hamilton's Depression Scale score,participants were classified into two cohort of depression(score 17)and no significant depression characteristics(score 17).Cardiac morphology and functional parameters were assessed using a combination of hyperechocardiocardiocardiography,heart magnetic resonance,and associated blood biomarkers.RESULTS The results of this study underscore the significant effects that depression can have on both the structure and function of the heart in patients with CHF.In particular,the individuals in the cohort with depression were 42.3%±6.7%of the individuals without depression vs 51.6%±5.9%,P<0.01)In comparison,the left ventricular ejection fraction,an important measure of contractional performance,was significantly reduced,underlining the harmful physiological interaction between mood disorders and cardiac efficiency.The measurement of the left ventricular end-diastolic diameter showed a significant expansion of the ventricular envelope in the depression group(68.2±7.5 mm vs 59.6±6.3 mm,P<0.01).Inflammatory markers,including high-sensitivity C-reactive protein(hs-CRP)and tumor necrosis factor-α(TNF-α),were significantly elevated in the depressed group(hs-CRP:8.7±2.3 mg/L vs 4.5±1.6 mg/L;TNF-α:42.5±7.6 pg/mL vs 28.3±5.4 pg/mL).Both B-type natriuretic peptide(1256±345 pg/mL vs 756±234 pg/mL)and angiotensin II(86.4±15.7 ng/mL vs 62.5±12.3 ng/mL)levels were significantly higher in the depressed group.CONCLUSION Among people with CHF,the presence of depressive symptoms appears to be closely related to pronounced changes in heart structure and impaired functional abilities.It is likely that depressive states contribute to the progress of heart reform and deterioration of left stomach function,possibly due to increased inflammatory cascades and increased activation of neuroendocrine regulatory pathways.展开更多
BACKGROUND Aortic adverse remodeling remains a critical complication following thoracic endovascular aortic repair(TEVAR)for Stanford type B aortic dissection(TBAD),significantly impacting long-term survival.Accurate ...BACKGROUND Aortic adverse remodeling remains a critical complication following thoracic endovascular aortic repair(TEVAR)for Stanford type B aortic dissection(TBAD),significantly impacting long-term survival.Accurate risk prediction is essential for optimized clinical management.AIM To develop and validate a logistic regression-based risk prediction model for aortic adverse remodeling following TEVAR in patients with TBAD.METHODS This retrospective observational cohort study analyzed 140 TBAD patients undergoing TEVAR at a tertiary center(2019–2024).Based on European guidelines,patients were categorized into adverse remodeling(aortic growth rate>2.9 mm/year,n=45)and favorable remodeling groups(n=95).Comprehensive variables(clinical/imaging/surgical)were analyzed using multivariable logistic regression to develop a predictive model.Model performance was assessed via receiver operating characteristic-area under the curve(AUC)and Hosmer-Lemeshow tests.RESULTS Multivariable analysis identified several strong independent predictors of negative aortic remodeling.Larger false lumen diameter at the primary entry tear[odds ratio(OR):1.561,95%CI:1.197–2.035;P=0.001]and patency of the false lumen(OR:5.639,95%CI:4.372-8.181;P=0.004)were significant risk factors.False lumen involvement extending to the thoracoabdominal aorta was identified as the strongest predictor,significantly increasing the risk of adverse remodeling(OR:11.751,95%CI:9.841-15.612;P=0.001).Conversely,false lumen involvement confined to the thoracic aorta demonstrated a significant protective effect(OR:0.925,95%CI:0.614–0.831;P=0.015).The prediction model exhibited excellent discrimination(AUC=0.968)and calibration(Hosmer-Lemeshow P=0.824).CONCLUSION This validated risk prediction model identifies aortic adverse remodeling with high accuracy using routinely available clinical parameters.False lumen involvement thoracoabdominal aorta is the strongest predictor(11.751-fold increased risk).The tool enables preoperative risk stratification to guide tailored TEVAR strategies and improve long-term outcomes.展开更多
Aneurysms and dissections represent some of the most serious cardiovascular diseases.The prevailing theory posits that mechanical overloading of the vessel wall is the underlying cause.Inspired by Barkhordarian et al,...Aneurysms and dissections represent some of the most serious cardiovascular diseases.The prevailing theory posits that mechanical overloading of the vessel wall is the underlying cause.Inspired by Barkhordarian et al,the authors present matrix metalloproteinases(MMPs)and their inhibitors in immunohistological analyses as contributing factors in the pathophysiology of aortic aneurysms(AA).Data analysis of MMP-1,MMP-9,tissue inhibitors of metalloproteinases(TIMPs),including TIMP-1 and TIMP-2 expression reveals a varied distribution between the adventitia and media and a non-uniform expression of the investigated markers.These elements,as key components of the extracellular matrix(ECM),indicate that the formation of AA is not solely driven by endoluminal pressure loading of the aortic wall.Instead,degenerative processes within ECM elements contribute significantly.Importantly,AA do not necessarily imply dissection.Tissue destruction,allowing blood flow entry,arises from reduced oxygen supply to the media,primarily due to incomplete capillarization or neocapillarization.展开更多
The paradigm-shifting efficacy of immune checkpoint inhibitors in microsatellite instability-high colorectal cancer demands a critical appraisal of their long-term tissue effects.This editorial is a landmark case repo...The paradigm-shifting efficacy of immune checkpoint inhibitors in microsatellite instability-high colorectal cancer demands a critical appraisal of their long-term tissue effects.This editorial is a landmark case report revealing spontaneous colonic transection following pathological complete response to pembrolizumab-a first-in-medicine finding.Despite radiological resolution of disease,profound immune-mediated tissue remodeling resulted in catastrophic structural failure at the tumor site.This phenomenon exposes critical limitations in current imaging modalities to detect immunotherapy-induced bowel wall fragility and necessitates heightened awareness among surgeons.As immune checkpoint inhibitors move into neoadjuvant settings with rising complete response rates,we must reassess surgical planning,consider prophylactic interventions for high-risk anatomy,and develop biomarkers for tissue integrity.This case underscores that tumor reg-ression does not equate to restored organ function,urging multidisciplinary vigilance against delayed structural toxicity.展开更多
The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is la...The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.展开更多
Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and infl...Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.展开更多
LIM zinc finger domain containing 1(LIMS1),an evolutionarily conserved LIM domain adaptor protein,is implicated in diverse pathologies,including cancer and neurological disorders.However,its roles in cardiac diseases ...LIM zinc finger domain containing 1(LIMS1),an evolutionarily conserved LIM domain adaptor protein,is implicated in diverse pathologies,including cancer and neurological disorders.However,its roles in cardiac diseases and the underlying mechanisms remain unclear.Here,we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure.We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy and murine cardiomyocytes,suggesting that LIMS1 dysregulation contributes to cardiac pathology.Using CRISPR/Cas9 technology,we generate a zebrafish model of lims1 loss-offunction mutant,which exhibits severe cardiac chamber remodeling,systolic dysfunction,and premature mortality,demonstrating the essential role of lims1 in maintaining cardiac integrity.Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1-deficient hearts.Strikingly,pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes.Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation,offering insights into cardiac remodeling and potential therapeutic strategies.展开更多
Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequentl...Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.展开更多
Background:Left atrioventricular coupling index(LACI)is a promising marker for predicting major adverse cardiac events in individuals with acute ST-segment elevation myocardial infarction(STEMI).However,the relationsh...Background:Left atrioventricular coupling index(LACI)is a promising marker for predicting major adverse cardiac events in individuals with acute ST-segment elevation myocardial infarction(STEMI).However,the relationship between LACI and adverse left ventricular(LV)remodeling(ALVR)in patients with STEMI remains to be fully elucidated.Methods:In this retrospective study,143 patients with STEMI who had undergone primary percutaneous coronary inter-vention(PCI)underwent cardiovascular magnetic resonance(CMR)imaging.The examinations were performed at 5±2 days(baseline)after PCI and at 6 months after STEMI.Left atrial and LV structural and functional indicators were evaluated.ALVR was defined as an increase of≥20%in LV end-diastolic volume(LVEDV)or an increase of≥15%in LV end-systolic volume at 6 months on CMR images.The patients were divided into two groups depending on the presence or absence of ALVR,and the CMR features were compared between the two groups.Results:Overall,51 patients(mean age 57±11 years;42 men)experienced ALVR after 6 months.In the univariable regression analysis,LVEDV index and LACI were significantly correlated with ALVR(odds ratio[OR]:0.989,95%confidence interval[CI]:0.979-0.999,p=0.025;OR:1.046,95%CI:1.012-1.080,p=0.007,respectively).Following adjustment for fundamental clinical variables,multivariate logistic regression analysis showed that baseline LACI was an independent predictor of ALVR at 6 months(OR:1.324,95%CI:1.055-1.662,p=0.016).Conclusions:CMR-derived LACI in patients with acute STEMI was an independent predictor of ALVR.展开更多
基金supported by Grant 3195 from Paralyzed Veterans of America Research Foundation (to BRK)
文摘The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.
基金supported by the National Natural Science Foundation of China (32072936 and 32273080)。
文摘Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.
文摘When mammals are exposed to cold,their metabolism undergoes substantial changes.The liver plays a central role in maintaining energy homeostasis by shifting from glucose metabolism to lipid catabolism.A recent study by Davidson et al.^([1]),published in Cell Metabolism,highlights a novel mechanism involving lysosomal lipid remodeling during cold adaptation.Specifically,the study reveals that cold exposure elevates hepatic levels of Bis(Monoacylglycerol)Phosphate(BMP)lipids,which are regulated by Transcription Factor EB(TFEB)and Phospholipase A2 group XV(PLA2G15).
基金Jiangxi Provincial Department of Education Science and Technology Project(Grant No.GJJ2401615)Jiangxi Provincial Department of Education Teaching Reform Project(Grant No.JXJG-24-15-15).
文摘The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced myocardial remodeling by activating the PI3K/AKT1 pathway.The cardiac function of mice was evaluated by echocardiography,revealing that MgIG could improve left ventricular function.Pathological staining analysis showed that MgIG could reduce the degree of myocardial injury caused by ISO.Serum data detected by ELISA demonstrated that MgIG could decrease the levels of CK-MB,MDA,and LDH while increasing the activity of GSH-Px.Western blotting analysis revealed that protein expression levels of Collagen I,BNP,Bax,cleaved caspase-3,p-PI3K,and p-AKT1 were decreased,whereas the protein expressions of Bcl-2,COX2,and SOD1 were increased upon MgIG treatment.However,the activation of the PI3K pathway reversed the cardioprotective effects of MgIG,as evidenced by the addition of PI3K activators.Taken together,our comprehensive results suggested that MgIG could improve ISO-induced myocardial remodeling,potentially through its mechanism of inhibiting the PI3K/AKT1 pathway to regulate apoptosis and oxidative stress.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
基金supported by the National Natural Science Foundation of China,Nos.82030071(to JH),82272495(to YC)Science and Technology Major Project of Changsha,No.kh2103008(to JH)Graduate Students’Independent Innovative Projects of Hunan Province,No.CX20230311(to YJ)。
文摘Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyladenosine(m^(6)A)modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes.However,whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown.We found that expression of methyltransferase 14 protein(METTL14)in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels.Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury.Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction,we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner,thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration.Finally,we administered syringin,a stabilizer of METTL14,using molecular docking.Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14.Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.
基金supported by National Key Research and Development Program of China(Grant Nos.:2024YFC3506500/01,and 2023YFA0914100)the National Natural Science Foundation of China(Grant Nos.:82425059,and 82173950).
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is characterized by hepatic steatosis and may progress to severe steatohepatitis with associated fibrosis[1].There is a notable lack of effective and widely accepted pharmacological interventions for MAFLD.The fruits of Forsythia suspensa has been used in the treatment of cholestatic liver injury,hepatitis,and liver fibrosis.However,the effective constituent remains unknown.
文摘Astrocytes and microglia are emerging key regulators of activity-dependent synapse remodeling that engulf and remove synapses in response to changes in neural activity.Yet,the degree to which these cells communicate to coordinate this process remains an open question.Here,we use whisker removal in postnatal mice to induce activity-dependent synapse removal in the barrel cortex.We show that astrocytes do not engulf synapses in this paradigm.Instead,astrocytes reduce contact with synapses prior to microglia-mediated synapse engulfment.
文摘Mechanical loading constitutes a fundamental determinant in the process of bone remodeling.This modeling encompasses the incorporation of mechanical stimuli,the involvement of cellular and molecular constituents,as well as the utilization of sophisticated computational methodologies.Such an approach is imperative for forecasting bone behaviour across varying environmental conditions.In the present study,key findings from bone mechanobiology are reviewed,along with the possibility that Functionally Graded Materials(FGM)enhances osseointegration and lowers the stress-shielding effect during bone remodeling and compared to titanium,FGM improves periprosthetic bone remodeling.To summarise some of the most important findings from computational models of bone mechanobiology,explaining how modifications to the mechanical environment affect implant design,growth of bone,and bone response.The impact that changes related to the mechanical environment have on bone response is examined using computational models and methods such as surface microtopography to determine how an implant’s bone density has increased over time.This review focuses on the refinement of advanced simulation frameworks and their synergy with imaging technologies to strengthen model validation,ultimately resulting in better clinical outcomes in the context of bone health treatments.
基金supported by the National Natural Science Foundation of China(32172389)the Excellent Youth Foundation of Henan Province,China(232300421029)the Key Research and Development Project of Henan Province,China(221111112200)。
文摘The insect fat body is comparable to the liver and adipose tissue in vertebrates,and plays a pivotal role in energy metabolism,nutrient storage,and reproduction.During metamorphosis,the fat body is disassembled via programmed cell death and cell dissociation.After adult eclosion,the fat body is reconstructed either by repopulation from the remaining juvenile fat body cells or by differentiation from adult progenitor cells.This reconstruction is a prerequisite for initiating the extensive synthesis of vitellogenin(Vg),which is necessary for the maturation of eggs.Despite its significance,the underlying mechanisms of this reconstruction remain inadequately understood.Transcriptome analysis of the fat bodies from migratory locusts at 0-5 days post adult emergence revealed 79 genes associated with chromatin remodeling.Weighted gene co-expression network analysis indicated a positive correlation between chromatin remodeling and fat body reconstitution.Protein-protein interaction analysis revealed that brahma,which encodes the catalytic subunit of the SWI/SNF chromatin remodeling complex,is crucial for post-adult-eclosion fat body development.qRT-PCR analysis demonstrated that the levels of brahma mRNA in the fat body are progressively increased during the previtellogenic stage,then reach the peak and remain elevated in the vitellogenic phase.Furthermore,brahma is expressed in response to gonadotropic juvenile hormone(JH).Knockdown of brahma led to a marked reduction in Vg expression within the fat body,along with arrested ovarian growth.These findings shed light on the involvement of brahmamediated chromatin remodeling in JH-stimulated fat body reconstruction and reproduction of adult female locusts.
文摘BACKGROUND Chronic heart failure(CHF)is a severe cardiovascular disease that significantly threatens human health.Depression,a common comorbidity,may substantially impact cardiac structure and function.However,the exact relationship between depression and cardiac remodeling and left ventricular functional changes remains incompletely understood.This study sets out to explore,with a clinically grounded perspective,how depressive states may subtly or profoundly influence the trajectory of cardiac remodeling and the functional dynamics of the left ventricle in individuals grappling with CHF.Beyond mere observation,it also aims to untangle the underlying physiological or neurohormonal pathways that might bridge emotional distress and cardiac dysfunction.AIM To delve into how depressive symptoms might shape the progression of cardiac remodeling and impair left ventricular function among individuals living with CHF.Particular attention is given to the role of inflammatory signaling and disruptions in neuroendocrine balance as possible mediating factors.By examining these intertwined physiological and psychological processes,the study seeks to shed light on the reciprocal link between emotional distress and CHF,offering insights that may inform more precise,mechanism-based treatment strategies.METHODS In this retrospective clinical trial,248 patients diagnosed with CHF were analyzed in the tertiary treatment center between January 2018 and December 2022.According to Hamilton's Depression Scale score,participants were classified into two cohort of depression(score 17)and no significant depression characteristics(score 17).Cardiac morphology and functional parameters were assessed using a combination of hyperechocardiocardiocardiography,heart magnetic resonance,and associated blood biomarkers.RESULTS The results of this study underscore the significant effects that depression can have on both the structure and function of the heart in patients with CHF.In particular,the individuals in the cohort with depression were 42.3%±6.7%of the individuals without depression vs 51.6%±5.9%,P<0.01)In comparison,the left ventricular ejection fraction,an important measure of contractional performance,was significantly reduced,underlining the harmful physiological interaction between mood disorders and cardiac efficiency.The measurement of the left ventricular end-diastolic diameter showed a significant expansion of the ventricular envelope in the depression group(68.2±7.5 mm vs 59.6±6.3 mm,P<0.01).Inflammatory markers,including high-sensitivity C-reactive protein(hs-CRP)and tumor necrosis factor-α(TNF-α),were significantly elevated in the depressed group(hs-CRP:8.7±2.3 mg/L vs 4.5±1.6 mg/L;TNF-α:42.5±7.6 pg/mL vs 28.3±5.4 pg/mL).Both B-type natriuretic peptide(1256±345 pg/mL vs 756±234 pg/mL)and angiotensin II(86.4±15.7 ng/mL vs 62.5±12.3 ng/mL)levels were significantly higher in the depressed group.CONCLUSION Among people with CHF,the presence of depressive symptoms appears to be closely related to pronounced changes in heart structure and impaired functional abilities.It is likely that depressive states contribute to the progress of heart reform and deterioration of left stomach function,possibly due to increased inflammatory cascades and increased activation of neuroendocrine regulatory pathways.
基金Supported by Zhangjiajie"Xiao He(Young Talent)"Project,No.2024XHRC03Jishou University School-Level Research Project.
文摘BACKGROUND Aortic adverse remodeling remains a critical complication following thoracic endovascular aortic repair(TEVAR)for Stanford type B aortic dissection(TBAD),significantly impacting long-term survival.Accurate risk prediction is essential for optimized clinical management.AIM To develop and validate a logistic regression-based risk prediction model for aortic adverse remodeling following TEVAR in patients with TBAD.METHODS This retrospective observational cohort study analyzed 140 TBAD patients undergoing TEVAR at a tertiary center(2019–2024).Based on European guidelines,patients were categorized into adverse remodeling(aortic growth rate>2.9 mm/year,n=45)and favorable remodeling groups(n=95).Comprehensive variables(clinical/imaging/surgical)were analyzed using multivariable logistic regression to develop a predictive model.Model performance was assessed via receiver operating characteristic-area under the curve(AUC)and Hosmer-Lemeshow tests.RESULTS Multivariable analysis identified several strong independent predictors of negative aortic remodeling.Larger false lumen diameter at the primary entry tear[odds ratio(OR):1.561,95%CI:1.197–2.035;P=0.001]and patency of the false lumen(OR:5.639,95%CI:4.372-8.181;P=0.004)were significant risk factors.False lumen involvement extending to the thoracoabdominal aorta was identified as the strongest predictor,significantly increasing the risk of adverse remodeling(OR:11.751,95%CI:9.841-15.612;P=0.001).Conversely,false lumen involvement confined to the thoracic aorta demonstrated a significant protective effect(OR:0.925,95%CI:0.614–0.831;P=0.015).The prediction model exhibited excellent discrimination(AUC=0.968)and calibration(Hosmer-Lemeshow P=0.824).CONCLUSION This validated risk prediction model identifies aortic adverse remodeling with high accuracy using routinely available clinical parameters.False lumen involvement thoracoabdominal aorta is the strongest predictor(11.751-fold increased risk).The tool enables preoperative risk stratification to guide tailored TEVAR strategies and improve long-term outcomes.
文摘Aneurysms and dissections represent some of the most serious cardiovascular diseases.The prevailing theory posits that mechanical overloading of the vessel wall is the underlying cause.Inspired by Barkhordarian et al,the authors present matrix metalloproteinases(MMPs)and their inhibitors in immunohistological analyses as contributing factors in the pathophysiology of aortic aneurysms(AA).Data analysis of MMP-1,MMP-9,tissue inhibitors of metalloproteinases(TIMPs),including TIMP-1 and TIMP-2 expression reveals a varied distribution between the adventitia and media and a non-uniform expression of the investigated markers.These elements,as key components of the extracellular matrix(ECM),indicate that the formation of AA is not solely driven by endoluminal pressure loading of the aortic wall.Instead,degenerative processes within ECM elements contribute significantly.Importantly,AA do not necessarily imply dissection.Tissue destruction,allowing blood flow entry,arises from reduced oxygen supply to the media,primarily due to incomplete capillarization or neocapillarization.
基金Supported by Beijing Tsinghua Changgung Hospital Youth Fund,No.12021C1011。
文摘The paradigm-shifting efficacy of immune checkpoint inhibitors in microsatellite instability-high colorectal cancer demands a critical appraisal of their long-term tissue effects.This editorial is a landmark case report revealing spontaneous colonic transection following pathological complete response to pembrolizumab-a first-in-medicine finding.Despite radiological resolution of disease,profound immune-mediated tissue remodeling resulted in catastrophic structural failure at the tumor site.This phenomenon exposes critical limitations in current imaging modalities to detect immunotherapy-induced bowel wall fragility and necessitates heightened awareness among surgeons.As immune checkpoint inhibitors move into neoadjuvant settings with rising complete response rates,we must reassess surgical planning,consider prophylactic interventions for high-risk anatomy,and develop biomarkers for tissue integrity.This case underscores that tumor reg-ression does not equate to restored organ function,urging multidisciplinary vigilance against delayed structural toxicity.
文摘The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.
基金supported by grants from National Natural Science Foundation of China(32125038)National Key Research and Development Program of China(grant number 2023YFD1801100 and 2023YFD1800804)+1 种基金the Key Research and Development Program of the Xinjiang Uygur Autonomous Region(No.2024B02016)the 2115 Talent Development Program of China Agricultural University.
文摘Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.
基金the National Natural Science Foundation of China(82070394,82371863,31970504,82100491,and 82000307)the Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control project(HPKL2023001)for their support of this research.
文摘LIM zinc finger domain containing 1(LIMS1),an evolutionarily conserved LIM domain adaptor protein,is implicated in diverse pathologies,including cancer and neurological disorders.However,its roles in cardiac diseases and the underlying mechanisms remain unclear.Here,we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure.We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy and murine cardiomyocytes,suggesting that LIMS1 dysregulation contributes to cardiac pathology.Using CRISPR/Cas9 technology,we generate a zebrafish model of lims1 loss-offunction mutant,which exhibits severe cardiac chamber remodeling,systolic dysfunction,and premature mortality,demonstrating the essential role of lims1 in maintaining cardiac integrity.Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1-deficient hearts.Strikingly,pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes.Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation,offering insights into cardiac remodeling and potential therapeutic strategies.
基金Supported by Science and Technology Department of Yunnan Province-Kunming Medical University,Kunming Medical Joint Special Project-Surface Project,No.202401AY070001-164Yunnan Provincial Clinical Research Center Cardiovascular Diseases-New Technology Research for Development Project for Diagnosis and Treatment Cardiovascular Diseases,No.202102AA310002the Key Technology Research and Device Development Project for Innovative Diagnosis and Treatment of Structural Heart Disease in the Southwest Plateau Region,No.202302AA310045.
文摘Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.
基金supported by the National Natural Science Foundation of China(Grant 82471937)Beijing Hospitals Authority Youth Programme(Grant QML20230610).
文摘Background:Left atrioventricular coupling index(LACI)is a promising marker for predicting major adverse cardiac events in individuals with acute ST-segment elevation myocardial infarction(STEMI).However,the relationship between LACI and adverse left ventricular(LV)remodeling(ALVR)in patients with STEMI remains to be fully elucidated.Methods:In this retrospective study,143 patients with STEMI who had undergone primary percutaneous coronary inter-vention(PCI)underwent cardiovascular magnetic resonance(CMR)imaging.The examinations were performed at 5±2 days(baseline)after PCI and at 6 months after STEMI.Left atrial and LV structural and functional indicators were evaluated.ALVR was defined as an increase of≥20%in LV end-diastolic volume(LVEDV)or an increase of≥15%in LV end-systolic volume at 6 months on CMR images.The patients were divided into two groups depending on the presence or absence of ALVR,and the CMR features were compared between the two groups.Results:Overall,51 patients(mean age 57±11 years;42 men)experienced ALVR after 6 months.In the univariable regression analysis,LVEDV index and LACI were significantly correlated with ALVR(odds ratio[OR]:0.989,95%confidence interval[CI]:0.979-0.999,p=0.025;OR:1.046,95%CI:1.012-1.080,p=0.007,respectively).Following adjustment for fundamental clinical variables,multivariate logistic regression analysis showed that baseline LACI was an independent predictor of ALVR at 6 months(OR:1.324,95%CI:1.055-1.662,p=0.016).Conclusions:CMR-derived LACI in patients with acute STEMI was an independent predictor of ALVR.
