Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications wit...Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
Recently,Prevotella spp.,a major genus of gram-negative commensal bacteria in humans,have emerged as a key microbial contributor to host metabolism due to its ability to ferment dietary fibers,produce beneficial short...Recently,Prevotella spp.,a major genus of gram-negative commensal bacteria in humans,have emerged as a key microbial contributor to host metabolism due to its ability to ferment dietary fibers,produce beneficial short-chain fatty acids,and influence immune responses.However,their diversity and functional differences have created challenges for their development and therapeutic use.Recent studies have shown that specific Prevotella species,such as P.copri,P.intestinalis,and P.histicola,can strengthen gut barrier integrity and reduce metabolic imbalances.Notably,Prevotella populations can be increased through high-fiber or herbal-based treatments.Traditional herbal medicines,including fiber-rich decoctions,also demonstrate the potential to boost endogenous Prevotella communities,enhance microbial fermentation,and improve glucose and lipid balance.This perspective examines the context-dependent roles of Prevotella spp.,with emphasis on the functional heterogeneity of key species such as P.copri,suggests a framework for combining herbal modulation with species-level microbiota profiling,and outlines a research plan to explore microbe-herb synergy in treating obesity,type 2 diabetes,and related metabolic disorders.This strategy offers a new,ecology-based approach to complement standard metabolic interventions.展开更多
Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzhe...Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the...Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.展开更多
Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensiv...Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.展开更多
Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and ...Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and substantially increase adverse cardiovascular outcomes.To describe this interplay,the American Heart Association(AHA)recently proposed the concept of cardiovascular-kidney-metabolic(CKM)syndrome^([1]).However,its risk-enhancing factors and underlying mechanisms remain unclear.展开更多
Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its glo...Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.展开更多
Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease,particularly metabolic dysfunction-associated steatohep-atitis(MASH),a progressive form of metabolic dysfunction-asso...Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease,particularly metabolic dysfunction-associated steatohep-atitis(MASH),a progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD).With the rising global prevalence of MASLD—affecting over one-third of the adult population—and its close association with obesity,insulin resistance,and metabolic syndrome,there is an urgent need for inno-vative,minimally invasive therapies that can reverse liver fibrosis and prevent progression to cirrhosis and hepatocellular carcinoma.Traditional management of MASLD relies on lifestyle modifications and bariatric surgery,yet these app-roaches are hampered by issues of adherence,invasiveness,and accessibility.This review examines endoscopic bariatric metabolic therapies including endoscopic sleeve gastroplasty(ESG),intragastric balloons(IGB),duodenal mucosal resur-facing(DMR),and duodeno-jejunal bypass liners(DJBL),as well as revisional procedures like endoscopic revisional gastroplasty(ERG)and transoral outlet reduction(TORe).Clinical studies and meta-analyses indicate that metabolic en-doscopy is safe and effective for liver fibrosis in MASH.ESG appears to offer the greatest fibrosis reduction,while IGB and DJBL yield modest improvements,and DMR shows no significant effect.Among revisional therapies,ERG has dem-onstrated fibrosis reduction,although the benefits of TORe remain to be fully evaluated.展开更多
Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and ...Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.展开更多
The global prevalence of metabolic-associated fatty liver disease(MAFLD)is on the rise,seriously threatening human health.Currently,no specific approved drugs are available for its treatment.This paper reviews the pat...The global prevalence of metabolic-associated fatty liver disease(MAFLD)is on the rise,seriously threatening human health.Currently,no specific approved drugs are available for its treatment.This paper reviews the pathogenesis of MAFLD,covering aspects like lipid accumulation and insulin resistance,oxidative stress,endoplasmic reticulum stress(ERS),lipotoxicity-induced hepatocyte damage,and fibrosis.It also elaborates on multiple treatment approaches for MAFLD,including metabolic regulation,improvement of the gut-liver axis interaction,modulation of immune and inflammatory pathways,enhancement of the adipose tissue-liver interaction,alleviation of fibrosis,prevention of hepatocyte injury,and traditional Chinese medicine(TCM)external therapies.Additionally,natural product research advancements,individual Chinese medicine components,and mixed herbal formulas for MAFLD treatment is provided.Many natural products and traditional Chinese medicines exhibit favorable effects in regulating lipid metabolism,anti-inflammation,and anti-oxidation,offering new directions and potential drug options for MAFLD treatment.This is expected to provide a reference for future clinical treatment and drug development.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
This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use o...This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has become a leading cause of liver-related morbidity worldwide.Despite broad consensus on the importance of diet in managing the disease,numerous myths a...Metabolic dysfunction-associated steatotic liver disease(MASLD)has become a leading cause of liver-related morbidity worldwide.Despite broad consensus on the importance of diet in managing the disease,numerous myths and miscon-ceptions persist among patients,healthcare professionals,and the general public.This article aims to critically review the main myths and facts surrounding the role of diet in MASLD,in light of the most current scientific evidence.展开更多
Gestational diabetes mellitus(GDM)is increasingly recognized not only for its immediate obstetric complications but also for its long-term metabolic consequences in both mothers and their offspring.Traditionally,resea...Gestational diabetes mellitus(GDM)is increasingly recognized not only for its immediate obstetric complications but also for its long-term metabolic consequences in both mothers and their offspring.Traditionally,research has emphasized the roles of pancreaticβ-cell dysfunction and placental dysregulation in GDM.However,emerging evidence highlights the maternal liver as a central metabolic hub during pregnancy coordinating glucose,lipid,and hormonal adaptations essential for fetal development.This review synthesizes current findings on how GDM disrupts the maternal liver’s adaptive roles,transforming it from a metabolic coordinator into a source of maladaptive endocrine,inflammatory,and nutrient signals.It outlines key mechanistic pathways through which maternal hepatic dysfunction may increase offspring susceptibility to non-alcoholic fatty liver disease and type 2 diabetes mellitus.These include hepatokine dysregulation,altered lipid metabolism,impaired insulin signaling,inflammatory and oxidative stress pathways,and epigenetic and transcriptomic reprogramming.In addition,it explores novel axes such as the gut-liver-placenta interplay,bile acid signaling disruptions,endoplasmic reticulum stress responses,and extracellular vesiclemediated communication.By reframing the maternal liver’s role in GDM pathophysiology,this review identifies critical windows for early clinical intervention and highlights the potential for liver-focused strategies to prevent the intergenerational transmission of metabolic disease.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease,affecting more than 30%of adults and 7%-14%of youths globally.MASLD and its advanced form of metabolic dysfunctio...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease,affecting more than 30%of adults and 7%-14%of youths globally.MASLD and its advanced form of metabolic dysfunctionassociated steatohepatitis(MASH)can progress to liver cirrhosis and hepatocellular carcinoma.Despite its growing burden,effective therapies for MASLD and MASH remain limited.Accumulating evidence indicates that short-chain fatty acids(SCFAs)modulate the activation of hepatic innate and adaptive immune cells,influencing liver inflammation and fibrosis.Moreover,SCFAs modulate liver lipid and glucose metabolism and insulin sensitivity,affecting MASLD progression.This review summarizes the cellular and molecular mechanisms through which SCFAs impact liver inflammation,fibrosis,and energy metabolism.Several key molecular signaling pathways are discussed.Clinical trials aiming to modulate SCFA production through different treatments are reviewed.Collectively,emerging evidence supports that targeting SCFA-mediated function represents a promising therapeutic strategy for MASLD and MASH.展开更多
Obesity is a major driver of metabolic dysfunction-associated steatotic liver disease(MASLD)and its progressive form,metabolic dysfunction-associated steatohepatitis(MASH).As the global prevalence of obesity continues...Obesity is a major driver of metabolic dysfunction-associated steatotic liver disease(MASLD)and its progressive form,metabolic dysfunction-associated steatohepatitis(MASH).As the global prevalence of obesity continues to rise,the burden of MASLD/MASH is increasing,posing significant challenges to healthcare systems.The use of anti-obesity medications(AOMs)in this population is complex due to altered hepatic metabolism,safety concerns,and potential hepatotoxicity.Recent advances in pharmacologic agents,such as glucagon-like peptide1(GLP-1)receptor agonists(GLP-1 RAs),dual GLP-1/glucose-gastric inhibitory polypeptide(GIP)agonists,and triple GLP-1/GIP/glucagon agonists,have shown promising metabolic effects in the general population.Among these,GLP-1 RAs(e.g.,liraglutide and semaglutide)consistently demonstrate hepatic benefits,including reductions in hepatic steatosis,improvements in liver enzyme profiles,and attenuation of fibrosis progression.Tirzepatide,a dual GLP-1/GIP agonist,has shown superior weight loss effects compared to GLP-1 receptor agonist monotherapy,with emerging but still limited data on hepatic outcomes in MASLD/MASH.Retatrutide,a triple agonist,has produced the most pronounced metabolic effects to date,although its impact on liver histology remains underexplored.Other AOMs,such as bupropion-naltrexone and phentermine-topiramate,require cautious use due to potential hepatotoxicity.Importantly,advanced MASLD may alter drug pharmacokinetics,underscoring the need for individualized therapy and close monitoring.This review provides an updated synthesis of the efficacy and safety of current and emerging AOMs in patients with MASLD/MASH and highlights the urgent need for further research to define optimal pharmacological strategies in this high-risk population.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highli...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.展开更多
This research is to explore the relationship between Helicobacter pylori (H. pylori)infection and the development of metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD), based on...This research is to explore the relationship between Helicobacter pylori (H. pylori)infection and the development of metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD), based on research by Ye et al.Their investigation analyzed the association of H. pylori infection with obesity,glucose, lipids, blood pressure, and MASLD in Chinese adults, through a crosssectionalstudy of 28624 participants. Clinical data analysis demonstrated thatH. pylori-positive participants exhibited significantly higher ages, blood glucose,total cholesterol, low-density lipoprotein, body mass index, systolic and diastolicblood pressure levels, and greater MASLD detection rates compare to the H. pylori-negative participants. These differences achieved statistical significance (P <0.05). Multivariate analysis identified, elevated glucose, body mass index, anddiastolic pressure as independent risk factors for H. pylori infection, while highdensitylipoprotein demonstrated protective effects. These findings suggest thatH. pylori infection may contribute to metabolic disturbances and MASLD.展开更多
Liver transplantation(LT)has significantly improved survival for patients with end-stage liver disease,but post-transplant metabolic syndrome(MetS)has emerged as a major challenge,affecting graft function and long-ter...Liver transplantation(LT)has significantly improved survival for patients with end-stage liver disease,but post-transplant metabolic syndrome(MetS)has emerged as a major challenge,affecting graft function and long-term outcomes.Characterized by obesity,dyslipidemia,hypertension,and insulin resistance,MetS increases the risk of cardiovascular disease,recurrent liver disease,and reduced graft survival.We systematically examine current literature on the diagnosis,risk stratification,and management of MetS in LT recipients,with a focus on lifestyle interventions,pharmacologic strategies,and potential modifications in immunosuppressive regimens.Additionally,we discuss the role of emerging therapies,including GLP-1 receptor agonists,PCSK-9 inhibitors,and bariatric interventions,in mitigating metabolic risk in this population.With cardiovascular complications being the leading cause of post-LT mortality,proactive management of MetS is crucial.A multidisciplinary approach integrating hepatology,endocrinology,and cardiology is essential to optimize patient outcomes.Future research should focus on personalized metabolic interventions and long-term strategies to enhance posttransplant survival and quality of life.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071383,82371392(to BN)the Natural Science Foundation of Shandong Province of China(Key Project),No.ZR2020KH007(to BN)+1 种基金“Taishan Scholar Distinguished Expert Program”of Shandong Province,No.tstp20231257(to BN)Health Commission Science and Technology Plan Project of Jinan,No.2023-1-8(to YZ).
文摘Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
基金supported by the National Research Foundation of Korea(2020R1F1A1074155).
文摘Recently,Prevotella spp.,a major genus of gram-negative commensal bacteria in humans,have emerged as a key microbial contributor to host metabolism due to its ability to ferment dietary fibers,produce beneficial short-chain fatty acids,and influence immune responses.However,their diversity and functional differences have created challenges for their development and therapeutic use.Recent studies have shown that specific Prevotella species,such as P.copri,P.intestinalis,and P.histicola,can strengthen gut barrier integrity and reduce metabolic imbalances.Notably,Prevotella populations can be increased through high-fiber or herbal-based treatments.Traditional herbal medicines,including fiber-rich decoctions,also demonstrate the potential to boost endogenous Prevotella communities,enhance microbial fermentation,and improve glucose and lipid balance.This perspective examines the context-dependent roles of Prevotella spp.,with emphasis on the functional heterogeneity of key species such as P.copri,suggests a framework for combining herbal modulation with species-level microbiota profiling,and outlines a research plan to explore microbe-herb synergy in treating obesity,type 2 diabetes,and related metabolic disorders.This strategy offers a new,ecology-based approach to complement standard metabolic interventions.
基金supported by National Institute on Aging(NIH-NIA)R01AG054459(to ALL).
文摘Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.
基金supported by a grant from the Dalian Science and Technology Innovation Fund Program(No.2024JJ13PT070)United Foundation for Dalian Institute of Chemical Physics,Chinese Academy of Sciences and the Second Hospital of Dalian Medical University(No.DMU-2&DICP UN202410)Dalian Life and Health Field Guidance Program Project(No.2024ZDJH01PT084).
文摘Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.
基金supported by the Natural Science Foundation of Beijing Municipality(Grant No.7234401)the Postdoctoral Research Foundation of China(Grant No.88014Y0226)。
文摘Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and substantially increase adverse cardiovascular outcomes.To describe this interplay,the American Heart Association(AHA)recently proposed the concept of cardiovascular-kidney-metabolic(CKM)syndrome^([1]).However,its risk-enhancing factors and underlying mechanisms remain unclear.
文摘Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.
文摘Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease,particularly metabolic dysfunction-associated steatohep-atitis(MASH),a progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD).With the rising global prevalence of MASLD—affecting over one-third of the adult population—and its close association with obesity,insulin resistance,and metabolic syndrome,there is an urgent need for inno-vative,minimally invasive therapies that can reverse liver fibrosis and prevent progression to cirrhosis and hepatocellular carcinoma.Traditional management of MASLD relies on lifestyle modifications and bariatric surgery,yet these app-roaches are hampered by issues of adherence,invasiveness,and accessibility.This review examines endoscopic bariatric metabolic therapies including endoscopic sleeve gastroplasty(ESG),intragastric balloons(IGB),duodenal mucosal resur-facing(DMR),and duodeno-jejunal bypass liners(DJBL),as well as revisional procedures like endoscopic revisional gastroplasty(ERG)and transoral outlet reduction(TORe).Clinical studies and meta-analyses indicate that metabolic en-doscopy is safe and effective for liver fibrosis in MASH.ESG appears to offer the greatest fibrosis reduction,while IGB and DJBL yield modest improvements,and DMR shows no significant effect.Among revisional therapies,ERG has dem-onstrated fibrosis reduction,although the benefits of TORe remain to be fully evaluated.
基金supported by the National Key Research and Development Program of China(No.2022YFC3702704)the National Natural Science Foundation of China(Nos.22376005,22076006 and 82073506).
文摘Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.
基金supported by the National Natural Science Foundation of China(82574477)the Jiangsu Provincial Traditional Chinese Medicine Science and Technology Development Plan(QN202426)+5 种基金Jiangsu Province“333 High-level Talents Training Project”((2024)3-0189)Youth Talent Support Project of the Jiangsu Association for Science and Technology(TJ-2023-053)Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials(KF202401)Fundamental Research Program of Shanxi Province(202403021221211)the research project supported by the Shanxi Scholarship Council of China(No.2023-158)Open Project of Key Laboratory of Tibetan Medicine Basic Research,Ministry of Education.
文摘The global prevalence of metabolic-associated fatty liver disease(MAFLD)is on the rise,seriously threatening human health.Currently,no specific approved drugs are available for its treatment.This paper reviews the pathogenesis of MAFLD,covering aspects like lipid accumulation and insulin resistance,oxidative stress,endoplasmic reticulum stress(ERS),lipotoxicity-induced hepatocyte damage,and fibrosis.It also elaborates on multiple treatment approaches for MAFLD,including metabolic regulation,improvement of the gut-liver axis interaction,modulation of immune and inflammatory pathways,enhancement of the adipose tissue-liver interaction,alleviation of fibrosis,prevention of hepatocyte injury,and traditional Chinese medicine(TCM)external therapies.Additionally,natural product research advancements,individual Chinese medicine components,and mixed herbal formulas for MAFLD treatment is provided.Many natural products and traditional Chinese medicines exhibit favorable effects in regulating lipid metabolism,anti-inflammation,and anti-oxidation,offering new directions and potential drug options for MAFLD treatment.This is expected to provide a reference for future clinical treatment and drug development.
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This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has become a leading cause of liver-related morbidity worldwide.Despite broad consensus on the importance of diet in managing the disease,numerous myths and miscon-ceptions persist among patients,healthcare professionals,and the general public.This article aims to critically review the main myths and facts surrounding the role of diet in MASLD,in light of the most current scientific evidence.
文摘Gestational diabetes mellitus(GDM)is increasingly recognized not only for its immediate obstetric complications but also for its long-term metabolic consequences in both mothers and their offspring.Traditionally,research has emphasized the roles of pancreaticβ-cell dysfunction and placental dysregulation in GDM.However,emerging evidence highlights the maternal liver as a central metabolic hub during pregnancy coordinating glucose,lipid,and hormonal adaptations essential for fetal development.This review synthesizes current findings on how GDM disrupts the maternal liver’s adaptive roles,transforming it from a metabolic coordinator into a source of maladaptive endocrine,inflammatory,and nutrient signals.It outlines key mechanistic pathways through which maternal hepatic dysfunction may increase offspring susceptibility to non-alcoholic fatty liver disease and type 2 diabetes mellitus.These include hepatokine dysregulation,altered lipid metabolism,impaired insulin signaling,inflammatory and oxidative stress pathways,and epigenetic and transcriptomic reprogramming.In addition,it explores novel axes such as the gut-liver-placenta interplay,bile acid signaling disruptions,endoplasmic reticulum stress responses,and extracellular vesiclemediated communication.By reframing the maternal liver’s role in GDM pathophysiology,this review identifies critical windows for early clinical intervention and highlights the potential for liver-focused strategies to prevent the intergenerational transmission of metabolic disease.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease,affecting more than 30%of adults and 7%-14%of youths globally.MASLD and its advanced form of metabolic dysfunctionassociated steatohepatitis(MASH)can progress to liver cirrhosis and hepatocellular carcinoma.Despite its growing burden,effective therapies for MASLD and MASH remain limited.Accumulating evidence indicates that short-chain fatty acids(SCFAs)modulate the activation of hepatic innate and adaptive immune cells,influencing liver inflammation and fibrosis.Moreover,SCFAs modulate liver lipid and glucose metabolism and insulin sensitivity,affecting MASLD progression.This review summarizes the cellular and molecular mechanisms through which SCFAs impact liver inflammation,fibrosis,and energy metabolism.Several key molecular signaling pathways are discussed.Clinical trials aiming to modulate SCFA production through different treatments are reviewed.Collectively,emerging evidence supports that targeting SCFA-mediated function represents a promising therapeutic strategy for MASLD and MASH.
文摘Obesity is a major driver of metabolic dysfunction-associated steatotic liver disease(MASLD)and its progressive form,metabolic dysfunction-associated steatohepatitis(MASH).As the global prevalence of obesity continues to rise,the burden of MASLD/MASH is increasing,posing significant challenges to healthcare systems.The use of anti-obesity medications(AOMs)in this population is complex due to altered hepatic metabolism,safety concerns,and potential hepatotoxicity.Recent advances in pharmacologic agents,such as glucagon-like peptide1(GLP-1)receptor agonists(GLP-1 RAs),dual GLP-1/glucose-gastric inhibitory polypeptide(GIP)agonists,and triple GLP-1/GIP/glucagon agonists,have shown promising metabolic effects in the general population.Among these,GLP-1 RAs(e.g.,liraglutide and semaglutide)consistently demonstrate hepatic benefits,including reductions in hepatic steatosis,improvements in liver enzyme profiles,and attenuation of fibrosis progression.Tirzepatide,a dual GLP-1/GIP agonist,has shown superior weight loss effects compared to GLP-1 receptor agonist monotherapy,with emerging but still limited data on hepatic outcomes in MASLD/MASH.Retatrutide,a triple agonist,has produced the most pronounced metabolic effects to date,although its impact on liver histology remains underexplored.Other AOMs,such as bupropion-naltrexone and phentermine-topiramate,require cautious use due to potential hepatotoxicity.Importantly,advanced MASLD may alter drug pharmacokinetics,underscoring the need for individualized therapy and close monitoring.This review provides an updated synthesis of the efficacy and safety of current and emerging AOMs in patients with MASLD/MASH and highlights the urgent need for further research to define optimal pharmacological strategies in this high-risk population.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.
基金Supported by National Natural Science Foundation of China,No.82270594.
文摘This research is to explore the relationship between Helicobacter pylori (H. pylori)infection and the development of metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD), based on research by Ye et al.Their investigation analyzed the association of H. pylori infection with obesity,glucose, lipids, blood pressure, and MASLD in Chinese adults, through a crosssectionalstudy of 28624 participants. Clinical data analysis demonstrated thatH. pylori-positive participants exhibited significantly higher ages, blood glucose,total cholesterol, low-density lipoprotein, body mass index, systolic and diastolicblood pressure levels, and greater MASLD detection rates compare to the H. pylori-negative participants. These differences achieved statistical significance (P <0.05). Multivariate analysis identified, elevated glucose, body mass index, anddiastolic pressure as independent risk factors for H. pylori infection, while highdensitylipoprotein demonstrated protective effects. These findings suggest thatH. pylori infection may contribute to metabolic disturbances and MASLD.
文摘Liver transplantation(LT)has significantly improved survival for patients with end-stage liver disease,but post-transplant metabolic syndrome(MetS)has emerged as a major challenge,affecting graft function and long-term outcomes.Characterized by obesity,dyslipidemia,hypertension,and insulin resistance,MetS increases the risk of cardiovascular disease,recurrent liver disease,and reduced graft survival.We systematically examine current literature on the diagnosis,risk stratification,and management of MetS in LT recipients,with a focus on lifestyle interventions,pharmacologic strategies,and potential modifications in immunosuppressive regimens.Additionally,we discuss the role of emerging therapies,including GLP-1 receptor agonists,PCSK-9 inhibitors,and bariatric interventions,in mitigating metabolic risk in this population.With cardiovascular complications being the leading cause of post-LT mortality,proactive management of MetS is crucial.A multidisciplinary approach integrating hepatology,endocrinology,and cardiology is essential to optimize patient outcomes.Future research should focus on personalized metabolic interventions and long-term strategies to enhance posttransplant survival and quality of life.
