This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwid...This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.展开更多
The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver en...The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.展开更多
BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty...BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.AIM To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.METHODS A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and NAFLD.External validation encompassed 172 participants.NAFLD patients were divided based on liver fibrosis scores.The analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.RESULTS Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific BAs.In UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative correlation.Levels ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in NAFLD.The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.CONCLUSION This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.展开更多
The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease...The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.展开更多
Fatty liver disease(FLD)is a highly prevalent pathological liver disorder.It has many and varied etiologies and has heterogeneous clinical course and outcome.Its proper nomenclature and classification have been proble...Fatty liver disease(FLD)is a highly prevalent pathological liver disorder.It has many and varied etiologies and has heterogeneous clinical course and outcome.Its proper nomenclature and classification have been problematic since its initial recognition.Traditionally,it was divided into two main categories:Alcoholassociated liver disease and nonalcoholic FLD(NAFLD).Among these,the latter condition has been plagued with nomenclature and classification issues.The two main objections to its use have been the use of negative(non-alcoholic)and stigmatizing(fatty)terms in its nomenclature.Numerous attempts were made to address these issues but none achieved universal acceptance.Just recently,NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific methodology.FLD has been renamed steatotic liver disease(SLD),and NAFLD as metabolic dysfunction-associated SLD.Metabolic dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic steatohepatitis.This is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research,diagnosis,treatment,and prognosis of the disease in the future.展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies...Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.展开更多
Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were establi...Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease worldwide,affecting about 1/4th of the global population and causing a huge global economic burden.To date,no drugs have been approve...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease worldwide,affecting about 1/4th of the global population and causing a huge global economic burden.To date,no drugs have been approved for the treatment of NAFLD,making the correction of unhealthy lifestyles the principle method of treatment.Identifying patients with poor adherence to lifestyle correction and attempting to improve their adherence are therefore very important.AIM To develop and validate a scale that can rapidly assess the adherence of patients with NAFLD to lifestyle interventions.METHODS The Exercise and Diet Adherence Scale(EDAS)was designed based on com-pilation using the Delphi method,and its reliability was subsequently evaluated.Demographic and laboratory indicators were measured,and patients completed the EDAS questionnaire at baseline and after 6 months.The efficacy of the EDAS was evaluated in the initial cohort.Subsequently,the efficacy of the EDAS was internally verified in a validation cohort.RESULTS The EDAS consisted of 33 items in six dimensions,with a total of 165 points.Total EDAS score correlated significantly with daily number of exercise and daily reduction in calorie intake(P<0.05 each),but not with overall weight loss.A total score of 116 was excellent in predicting adherence to daily reduction in calorie intake(>500 kacl/d),(sensitivity/specificity was 100.0%/75.8%),while patients score below 97 could nearly rule out the possibility of daily exercise(sensitivity/specificity was 89.5%/44.4%).Total EDAS scores≥116,97-115,and<97 points were indicative of good,average,and poor adherence,respectively,to diet and exercise recommendations.CONCLUSION The EDAS can reliably assess the adherence of patients with NAFLD to lifestyle interventions and have clinical application in this population.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(N...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.展开更多
Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver diseas...Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.展开更多
The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbio...The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.展开更多
Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves o...Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.展开更多
Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH ...Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.展开更多
The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A com...The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.展开更多
BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations ...BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.展开更多
Colorectal cancer(CRC)belongs to the class of significantly malignant tumors found in humans.Recently,dysregulated fatty acid metabolism(FAM)has been a topic of attention due to its modulation in cancer,specifically C...Colorectal cancer(CRC)belongs to the class of significantly malignant tumors found in humans.Recently,dysregulated fatty acid metabolism(FAM)has been a topic of attention due to its modulation in cancer,specifically CRC.However,the regulatory FAM pathways in CRC require comprehensive elucidation.Methods:The clinical and gene expression data of 175 fatty acid metabolic genes(FAMGs)linked with colon adenocarcinoma(COAD)and normal cornerstone genes were gathered through The Cancer Genome Atlas(TCGA)-COAD corroborating with the Molecular Signature Database v7.2(MSigDB).Initially,crucial prognostic genes were selected by uni-and multi-variate Cox proportional regression analyses;then,depending upon these identified signature genes and clinical variables,a nomogram was generated.Lastly,to assess tumor immune characteristics,concomitant evaluation of tumor immune evasion/risk scoring were elucidated.Results:A 8-gene signature,including ACBD4,ACOX1,CD36,CPT2,ELOVL3,ELOVL6,ENO3,and SUCLG2,was generated,and depending upon this,CRC patients were categorized within high-risk(H-R)and low-risk(L-R)cohorts.Furthermore,risk and age-based nomograms indicated moderate discrimination and good calibration.The data confirmed that the 8-gene model efficiently predicted CRC patients’prognosis.Moreover,according to the conjoint analysis of tumor immune evasion and the risk scorings,the H-R cohort had an immunosuppressive tumor microenvironment,which caused a substandard prognosis.Conclusion:This investigation established a FAMGs-based prognostic model with substantially high predictive value,providing the possibility for improved individualized treatment for CRC individuals.展开更多
This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and ...This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.展开更多
In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2...In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.展开更多
BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been hig...BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence.AIM To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization(MR)design.METHODS The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators,including hip circumference(HC),waist circumference(WC),waist-to-hip ratio(WHR),body mass index(BMI),and body fat percentage(BF).Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium.Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables.Univariable MR(UVMR)and multivariable MR(MVMR)designs with analytical approaches,including inverse variance weighted(IVW),MR-Egger,weighted median(WM),and weighted mode methods,were used to assess the causal relationships between anthropometric indicators and NAFLD.RESULTS Causal relationships were revealed by UVMR,indicating that a higher risk of NAFLD was associated with a perunit increase in WC[IVW:odds ratio(OR)=2.67,95%CI:1.42-5.02,P=2.25×10^(−3)],and BF was causally associated with an increased risk of NAFLD(WM:OR=2.23,95%CI:1.07-4.66,P=0.033).The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking.However,no causal association between BF and NAFLD was observed.In addition,other causal relationships of HC,WHR(BMI adjusted),and BMI with the risk of NAFLD were not retained after FDR correction.CONCLUSION This study establishes a causal relationship,indicating that an increase in WC is associated with a higher risk of NAFLD.This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.展开更多
基金Supported by National Natural Science Foundation of China,No.82000625the Doctoral Scientific Research Foundation of Liaoning Province,No.2020-BS-109.
文摘This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.
文摘The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.
基金Supported by the Scientific Research Projects of Jiangsu Provincial Health and Health Commission,No.ZDB2020034 and No.M2021056.
文摘BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.AIM To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.METHODS A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and NAFLD.External validation encompassed 172 participants.NAFLD patients were divided based on liver fibrosis scores.The analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.RESULTS Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific BAs.In UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative correlation.Levels ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in NAFLD.The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.CONCLUSION This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.
文摘The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.
文摘Fatty liver disease(FLD)is a highly prevalent pathological liver disorder.It has many and varied etiologies and has heterogeneous clinical course and outcome.Its proper nomenclature and classification have been problematic since its initial recognition.Traditionally,it was divided into two main categories:Alcoholassociated liver disease and nonalcoholic FLD(NAFLD).Among these,the latter condition has been plagued with nomenclature and classification issues.The two main objections to its use have been the use of negative(non-alcoholic)and stigmatizing(fatty)terms in its nomenclature.Numerous attempts were made to address these issues but none achieved universal acceptance.Just recently,NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific methodology.FLD has been renamed steatotic liver disease(SLD),and NAFLD as metabolic dysfunction-associated SLD.Metabolic dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic steatohepatitis.This is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research,diagnosis,treatment,and prognosis of the disease in the future.
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
文摘Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.
基金supported by the National Natural Science Foundation of China(81971875,82300661)Natural Science Foundation of Anhui province(2308085QH246)+3 种基金Natural Science Foundation of the Anhui Higher Education Institutions(KJ2021A0205)Basic and Clinical Cooperative Research Program of Anhui Medical University(2019xkjT002,2019xkjT022,2022xkjT013)Talent Training Program,School of Basic Medical Sciences,Anhui Medical University(2022YPJH102)National College Students Innovation and Entrepreneurship Training Program of China(202210366024)。
文摘Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.
基金the Science and Technology Foundation of Tianjin Municipal Health Bureau,No.12KG119Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-059B+1 种基金Tianjin Health Science and Technology Project key discipline special,No.TJWJ2022XK034Research project of Chinese traditional medicine and Chinese traditional medicine combined with Western medicine of Tianjin municipal health and Family Planning Commission,No.2021022.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease worldwide,affecting about 1/4th of the global population and causing a huge global economic burden.To date,no drugs have been approved for the treatment of NAFLD,making the correction of unhealthy lifestyles the principle method of treatment.Identifying patients with poor adherence to lifestyle correction and attempting to improve their adherence are therefore very important.AIM To develop and validate a scale that can rapidly assess the adherence of patients with NAFLD to lifestyle interventions.METHODS The Exercise and Diet Adherence Scale(EDAS)was designed based on com-pilation using the Delphi method,and its reliability was subsequently evaluated.Demographic and laboratory indicators were measured,and patients completed the EDAS questionnaire at baseline and after 6 months.The efficacy of the EDAS was evaluated in the initial cohort.Subsequently,the efficacy of the EDAS was internally verified in a validation cohort.RESULTS The EDAS consisted of 33 items in six dimensions,with a total of 165 points.Total EDAS score correlated significantly with daily number of exercise and daily reduction in calorie intake(P<0.05 each),but not with overall weight loss.A total score of 116 was excellent in predicting adherence to daily reduction in calorie intake(>500 kacl/d),(sensitivity/specificity was 100.0%/75.8%),while patients score below 97 could nearly rule out the possibility of daily exercise(sensitivity/specificity was 89.5%/44.4%).Total EDAS scores≥116,97-115,and<97 points were indicative of good,average,and poor adherence,respectively,to diet and exercise recommendations.CONCLUSION The EDAS can reliably assess the adherence of patients with NAFLD to lifestyle interventions and have clinical application in this population.
基金Supported by National Institute of Environmental Health,No.R01ES030691No.R01ES030364,No.R01ES029944,No.U01HG013288,No.T32-ES013678,No.P30ES007048,No.U2CES030859,No.R01ES032831,No.R01ES033688,No.P30ES023515,and No.P2CES033433+8 种基金National Human Genome Research Institute and National Institute of Environmental Health,No.U01HG013288California Environmental Protection Agency,No.20-E0017National Cancer Institute and National Institute of Environmental Health,No.P01CA196569Ministry of Science and Innovation and State Research Agency,No.CEX2018-000806-SEuropean Union(“NextGenerationEU/PRTR”),No.IJC2020-043630-IEuropean Union’s Horizon Europe Research And Innovation Programme Under the Marie Skłodowska-Curie Actions Postdoctoral Fellowships,No.101059245United States Department of Agriculture,No.6250-51000-053National Institutes of Health,No.R01DK128117-01A1The Teen-LABS Consortium:National Institute of Diabetes and Digestive and Kidney Diseases,No.UM1DK072493 and No.UM1DK095710.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.
文摘Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.
基金the National Natural Science Foundation of China,No.82104525the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.21KJB360009Health Commission of Zhejiang Province Scientific Research Foundation,No.2024KY247.
文摘The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.
基金funded by grants from the National Key R&D Program of China(2016YFD0500604)。
文摘Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.
文摘Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.
基金supported by National Natural Science Foundation of China(NSFC:82073538 and 81773433)by the 2018 Chinese Nutrition Society(CNS)Nutrition Research Foundation-DSM Research Fund(CNS-DSM2018A30)。
文摘The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.
基金National Natural Science Foundation of China,No.72101236China Postdoctoral Science Foundation,No.2022M722900+1 种基金Collaborative Innovation Project of Zhengzhou City,No.XTCX2023006Nursing Team Project of the First Affiliated Hospital of Zhengzhou University,No.HLKY2023005.
文摘BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.
基金supported by the Doctoral Fund of Jining No.1 People’s Hospital(2021-BS-002).
文摘Colorectal cancer(CRC)belongs to the class of significantly malignant tumors found in humans.Recently,dysregulated fatty acid metabolism(FAM)has been a topic of attention due to its modulation in cancer,specifically CRC.However,the regulatory FAM pathways in CRC require comprehensive elucidation.Methods:The clinical and gene expression data of 175 fatty acid metabolic genes(FAMGs)linked with colon adenocarcinoma(COAD)and normal cornerstone genes were gathered through The Cancer Genome Atlas(TCGA)-COAD corroborating with the Molecular Signature Database v7.2(MSigDB).Initially,crucial prognostic genes were selected by uni-and multi-variate Cox proportional regression analyses;then,depending upon these identified signature genes and clinical variables,a nomogram was generated.Lastly,to assess tumor immune characteristics,concomitant evaluation of tumor immune evasion/risk scoring were elucidated.Results:A 8-gene signature,including ACBD4,ACOX1,CD36,CPT2,ELOVL3,ELOVL6,ENO3,and SUCLG2,was generated,and depending upon this,CRC patients were categorized within high-risk(H-R)and low-risk(L-R)cohorts.Furthermore,risk and age-based nomograms indicated moderate discrimination and good calibration.The data confirmed that the 8-gene model efficiently predicted CRC patients’prognosis.Moreover,according to the conjoint analysis of tumor immune evasion and the risk scorings,the H-R cohort had an immunosuppressive tumor microenvironment,which caused a substandard prognosis.Conclusion:This investigation established a FAMGs-based prognostic model with substantially high predictive value,providing the possibility for improved individualized treatment for CRC individuals.
基金the National Natural Science Foundation of China(Grant Nos.82072816 and 81672553)the Natural Science Foundation of Shandong Province(Grant No.ZR2021LZY003).
文摘This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.
基金Supported by the Kuwait Foundation for the Advancement of Sciences(KFAS)and Dasman Diabetes Institute,No.RACB-2021-007.
文摘In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.
基金Supported by Science and Technology Research Project of Sichuan Administration of Traditional Chinese Medicine,No.2023MS419.
文摘BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence.AIM To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization(MR)design.METHODS The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators,including hip circumference(HC),waist circumference(WC),waist-to-hip ratio(WHR),body mass index(BMI),and body fat percentage(BF).Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium.Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables.Univariable MR(UVMR)and multivariable MR(MVMR)designs with analytical approaches,including inverse variance weighted(IVW),MR-Egger,weighted median(WM),and weighted mode methods,were used to assess the causal relationships between anthropometric indicators and NAFLD.RESULTS Causal relationships were revealed by UVMR,indicating that a higher risk of NAFLD was associated with a perunit increase in WC[IVW:odds ratio(OR)=2.67,95%CI:1.42-5.02,P=2.25×10^(−3)],and BF was causally associated with an increased risk of NAFLD(WM:OR=2.23,95%CI:1.07-4.66,P=0.033).The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking.However,no causal association between BF and NAFLD was observed.In addition,other causal relationships of HC,WHR(BMI adjusted),and BMI with the risk of NAFLD were not retained after FDR correction.CONCLUSION This study establishes a causal relationship,indicating that an increase in WC is associated with a higher risk of NAFLD.This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.
