Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remai...Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.展开更多
[Objective]Leaf diseases significantly affect both the yield and quality of tea throughout the year.To address the issue of inadequate segmentation finesse in the current tea spot segmentation models,a novel diagnosis...[Objective]Leaf diseases significantly affect both the yield and quality of tea throughout the year.To address the issue of inadequate segmentation finesse in the current tea spot segmentation models,a novel diagnosis of the severity of tea spots was proposed in this research,designated as MDC-U-Net3+,to enhance segmentation accuracy on the base framework of U-Net3+.[Methods]Multi-scale feature fusion module(MSFFM)was incorporated into the backbone network of U-Net3+to obtain feature information across multiple receptive fields of diseased spots,thereby reducing the loss of features within the encoder.Dual multi-scale attention(DMSA)was incorporated into the skip connection process to mitigate the segmentation boundary ambiguity issue.This integration facilitates the comprehensive fusion of fine-grained and coarse-grained semantic information at full scale.Furthermore,the segmented mask image was subjected to conditional random fields(CRF)to enhance the optimization of the segmentation results[Results and Discussions]The improved model MDC-U-Net3+achieved a mean pixel accuracy(mPA)of 94.92%,accompanied by a mean Intersection over Union(mIoU)ratio of 90.9%.When compared to the mPA and mIoU of U-Net3+,MDC-U-Net3+model showed improvements of 1.85 and 2.12 percentage points,respectively.These results illustrated a more effective segmentation performance than that achieved by other classical semantic segmentation models.[Conclusions]The methodology presented herein could provide data support for automated disease detection and precise medication,consequently reducing the losses associated with tea diseases.展开更多
Thrombospondin 4(THBS4;TSP4),a crucial component of the extracellular matrix(ECM),serves as an important regulator of tissue homeostasis and various pathophysiological processes.As a member of the evolutionarily conse...Thrombospondin 4(THBS4;TSP4),a crucial component of the extracellular matrix(ECM),serves as an important regulator of tissue homeostasis and various pathophysiological processes.As a member of the evolutionarily conserved thrombospondin family,THBS4 is a multidomain adhesive glycoprotein characterized by six distinct structural domains that mediate its diverse biological functions.Through dynamic interactions with various ECM components,THBS4 plays pivotal roles in cell adhesion,proliferation,inflammation regulation,and tissue remodeling,establishing it as a key modulator of microenvironmental organization.The transcription and translation of THBS4 gene,as well as the activity of the THBS4 protein,are tightly regulated by multiple signaling pathways and extracellular cues.Positive regulators of THBS4 include transforming growth factorβ(TGF-β),interferonγ(IFNγ),granulocyte-macrophage colony-stimulating factor(GM-CSF),bone morphogenetic proteins(BMP12/13),and other regulatory factors(such as B4GALNT1,ITGA2/ITGB1,PDGFRβ,etc.),which upregulate THBS4 at the mRNA and/or protein level.Conversely,oxidized low-density lipoprotein(OXLDL)acts as a potent negative regulator of THBS4.This intricate regulatory network ensures precise spatial and temporal control of THBS4 expression in response to diverse physiological and pathological stimuli.Functionally,THBS4 acts as a critical signaling hub,influencing multiple downstream pathways essential for cellular behavior and tissue homeostasis.The best-characterized pathways include:(1)the PI3K/AKT/mTOR axis,which THBS4 modulates through both direct and indirect interactions with integrins and growth factor receptors;(2)Wnt/β-catenin signaling,where THBS4 functions as either an activator or inhibitor depending on the cellular context;(3)the suppression of DBET/TRIM69,contributing to its diverse regulatory roles.These signaling connections position THBS4 as a master regulator of cellular responses to microenvironmental changes.Substantial evidence links aberrant THBS4 expression to a range of pathological conditions,including neoplastic diseases,cardiovascular disorders,fibrotic conditions,neurodegenerative diseases,musculoskeletal disorders,and atopic dermatitis.In cancer biology,THBS4 exhibits context-dependent roles,functioning either as a tumor suppressor or promoter depending on the tumor type and microenvironment.In the cardiovascular system,THBS4 contributes to both adaptive remodeling and maladaptive fibrotic responses.Its involvement in fibrotic diseases arises from its ability to regulate ECM deposition and turnover.The diagnostic and therapeutic potential of THBS4 is particularly promising in oncology and cardiovascular medicine.As a biomarker,THBS4 expression patterns correlate significantly with disease progression and patient outcomes.Therapeutically,targeting THBS4-mediated pathways offers novel opportunities for precision medicine approaches,including anti-fibrotic therapies,modulation of the tumor microenvironment,and enhancement of tissue repair.This comprehensive review systematically explores three key aspects of THBS4 research:(1)the fundamental biological functions of THBS4 in ECM organization;(2)its mechanistic involvement in various disease pathologies;(3)its emerging potential as both a diagnostic biomarker and therapeutic target.By integrating recent insights from molecular studies,animal models,and clinical investigations,this review provides a framework for understanding the multifaceted roles of THBS4 in health and disease.The synthesis of current knowledge highlights critical research gaps and future directions for exploring THBS4-targeted interventions across multiple disease contexts.Given its unique position at the intersection of ECM biology and cellular signaling,THBS4 represents a promising frontier for the development of novel diagnostic tools and therapeutic strategies in precision medicine.展开更多
Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,n...Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.展开更多
Cardiovascular disease(CVD)remains one of the leading causes of mortality among adults globally,with continuously rising morbidity and mortality rates.Metabolic disorders are closely linked to various cardiovascular d...Cardiovascular disease(CVD)remains one of the leading causes of mortality among adults globally,with continuously rising morbidity and mortality rates.Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression,involving multifaceted mechanisms such as altered substrate utilization,mitochondrial structural and functional dysfunction,and impaired ATP synthesis and transport.In recent years,the potential role of peroxisome proliferator-activated receptors(PPARs)in cardiovascular diseases has garnered significant attention,particularly peroxisome proliferator-activated receptor alpha(PPARα),which is recognized as a highly promising therapeutic target for CVD.PPARαregulates cardiovascular physiological and pathological processes through fatty acid metabolism.As a ligand-activated receptor within the nuclear hormone receptor family,PPARαis highly expressed in multiple organs,including skeletal muscle,liver,intestine,kidney,and heart,where it governs the metabolism of diverse substrates.Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions,PPARαexerts its cardioprotective effects through multiple pathways:modulating lipid metabolism,participating in cardiac energy metabolism,enhancing insulin sensitivity,suppressing inflammatory responses,improving vascular endothelial function,and inhibiting smooth muscle cell proliferation and migration.These mechanisms collectively reduce the risk of cardiovascular disease development.Thus,PPARαplays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation,anti-inflammatory actions,and anti-apoptotic effects.PPARαis activated by binding to natural or synthetic lipophilic ligands,including endogenous fatty acids and their derivatives(e.g.,linoleic acid,oleic acid,and arachidonic acid)as well as synthetic peroxisome proliferators.Upon ligand binding,PPARαactivates the nuclear receptor retinoid X receptor(RXR),forming a PPARα-RXR heterodimer.This heterodimer,in conjunction with coactivators,undergoes further activation and subsequently binds to peroxisome proliferator response elements(PPREs),thereby regulating the transcription of target genes critical for lipid and glucose homeostasis.Key genes include fatty acid translocase(FAT/CD36),diacylglycerol acyltransferase(DGAT),carnitine palmitoyltransferase I(CPT1),and glucose transporter(GLUT),which are primarily involved in fatty acid uptake,storage,oxidation,and glucose utilization processes.Advancing research on PPARαas a therapeutic target for cardiovascular diseases has underscored its growing clinical significance.Currently,PPARαactivators/agonists,such as fibrates(e.g.,fenofibrate and bezafibrate)and thiazolidinediones,have been extensively studied in clinical trials for CVD prevention.Traditional PPARαagonists,including fenofibrate and bezafibrate,are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol(HDL-C)levels.These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα,and their cardioprotective effects have been validated in numerous clinical studies.Recent research highlights that fibrates improve insulin resistance,regulate lipid metabolism,correct energy metabolism imbalances,and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells,thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure.Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications,activating PPARαmay serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy,atherosclerosis,ischemic cardiomyopathy,myocardial infarction,diabetic cardiomyopathy,and heart failure.This review comprehensively examines the regulatory roles of PPARαin cardiovascular diseases and evaluates its clinical application value,aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.展开更多
Parkinson’s disease(PD)is a common neurodegenerative disorder with profound impact on patients’quality of life and long-term health,and early detection and intervention are particularly critical.In recent years,the ...Parkinson’s disease(PD)is a common neurodegenerative disorder with profound impact on patients’quality of life and long-term health,and early detection and intervention are particularly critical.In recent years,the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD.In this paper,we systematically evaluated potential biomarkers,including proteins,metabolites,epigenetic markers,and exosomes,in the peripheral blood of PD patients.Protein markers are one of the main directions of biomarker research in PD.In particular,α‑synuclein and its phosphorylated form play a key role in the pathological process of PD.It has been shown that aggregation ofα-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD.In terms of metabolites,uric acid,as a metabolite,plays an important role in oxidative stress and neuroprotection in PD.It has been found that changes in uric acid levels may be associated with the onset and progression of PD,showing its potential as an early diagnostic marker.Epigenetic markers,such as DNA methylation modifications and miRNAs,have also attracted much attention in Parkinson’s disease research.Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease,providing new research perspectives for the early diagnosis of PD.In addition,exosomes,as a potential biomarker carrier for PD,are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation.Studies have shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide a new breakthrough for early diagnosis.It has been shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide new breakthroughs in early diagnosis.In summary,through in-depth evaluation of biomarkers in the peripheral blood of PD patients,this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms.Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.展开更多
Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)hav...Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.展开更多
Objective:To evaluate the predictive value of the neutrophil⁃to⁃lymphocyte ratio(NLR)and the systemic immune⁃inflammation index(SII)in predicting patients with anti⁃melanoma differentiation⁃associated gene 5⁃positive(...Objective:To evaluate the predictive value of the neutrophil⁃to⁃lymphocyte ratio(NLR)and the systemic immune⁃inflammation index(SII)in predicting patients with anti⁃melanoma differentiation⁃associated gene 5⁃positive(anti⁃MDA5+)dermatomyositis(DM)develop into the rapidly progressive interstitial lung disease(RPILD).Methods:We retrospectively analyzed the clinical and laboratory data of 124 anti⁃MDA5+DM patients from the First Affiliated Hospital of Nanjing Medical University between March 2019 and September 2023.We identified independent risk factors associated with the development and mortality of RPILD with the Cox regression analysis,and determined the optimal cut⁃off values for predicting adverse outcomes with the receiver operating characteristic(ROC)curve analysis.Results:Among the 124 patients,36 patients(29.03%)developed RPILD,and 39 patients(31.45%)died during the follow⁃up period.The results of multivariate Cox regression analysis showed that the elevated NLR was an independent risk factor for RPILD development,while the elevated SII expression was independently associated with the increased mortality of RPILD.Based on the ROC curve analysis,NLR>6.12 was a predictor for RPILD,and SII>875.79 was associated with increased mortality risk of RPILD.Conclusion:Both NLR and SII are accessible,cost⁃effective,and reliable prognostic indicators for the prognosis of patients with anti⁃MDA5^(+)DM,providing a valuable guidance for clinical management and risk stratification of the disease.展开更多
Currently,research on N^(6)-methyladenine(m^(6)A)is extensive in the field of oncology,while studies involving m^(6)A and skin diseases remain relatively limited.Based on existing reports,we searched PubMed and Web of...Currently,research on N^(6)-methyladenine(m^(6)A)is extensive in the field of oncology,while studies involving m^(6)A and skin diseases remain relatively limited.Based on existing reports,we searched PubMed and Web of Science for literature related to m^(6)A and dermatological conditions.Analysis of citation counts and journal impact factors revealed a significant upward trend in the volume of m^(6)A-related research.Term frequency analysis of titles and abstracts indicated that studies mainly focus on skin tumors and inflammatory or immune-related skin diseases,particularly melanoma,psoriasis,and skin development.Transcriptomic data from the Gene Expression Omnibus(GEO)were analyzed,revealing differential expression of m^(6)A-related genes in 4 types of skin tumors(including squamous cell carcinoma and basal cell carcinoma)as well as in inflammatory skin diseases such as psoriasis and atopic dermatitis,and potential mechanisms of action were also explored.Findings suggest that m^(6)A modifications exhibit heterogeneity between neoplastic and nonneoplastic skin diseases.However,the regulatory mechanisms of m^(6)A dynamic modifications on key genes involved in dermatological disorders remain unclear and warrant further investigation.展开更多
Verticillium wilt,caused by the infamous pathogen Verticillium dahliae,presents a primary constraint on cotton cul-tivation worldwide.The complexity of disease resistance in cotton and the largely unexplored interacti...Verticillium wilt,caused by the infamous pathogen Verticillium dahliae,presents a primary constraint on cotton cul-tivation worldwide.The complexity of disease resistance in cotton and the largely unexplored interaction dynamics between the cotton plant host and V.dahliae pathogen pose a crucial predicament for effectively managing cotton Verticillium wilt.Nevertheless,the most cost-effective approach to controlling this disease involves breeding and cul-tivating resistant cotton varieties,demanding a meticulous analysis of the mechanisms underlying cotton’s resistance to Verticillium wilt and the identification of pivotal genes.These aspects constitute focal points in disease-resistance breeding programs.In this review,we comprehensively discuss genetic inheritance associated with Verticillium wilt resistance in cotton,the advancements in molecular markers for disease resistance,the functional investiga-tion of resistance genes in cotton,the analysis of pathogenicity genes in V.dahliae,as well as the intricate interplay between cotton and this fungus.Moreover,we delve into the future prospects of cutting-edge research on cotton Verticillium wilt,aiming to proffer valuable insights for the effective management of this devastating fungus.展开更多
Soybean frogeye leaf spot(FLS)disease is a worldwide disease caused by Cercospora sojina Hara.It is one of the major diseases suffered by soybean during the growth cycle,which seriously damages the yield and seed qual...Soybean frogeye leaf spot(FLS)disease is a worldwide disease caused by Cercospora sojina Hara.It is one of the major diseases suffered by soybean during the growth cycle,which seriously damages the yield and seed quality of soybean.The current resistant varieties are difficult to meet the production demand.The breeders have identified 50 different physiological small species and discussed the physiological and biochemical characteristics of soybean resistance to FLS.In soybean disease resistance breeding,resistance resources are screened for the main physiological races in different countries,resistance materials are created,more than 100 genome regions associated with resistance are located,and 12 resistance-related genes are identified.In order to promote the research of soybean disease resistance breeding,this paper expounded and analyzed the pathogenesis characteristics of soybean FLS,the division of races,the physiological and biochemical mechanism of soybean resistance to FLS disease,quantitative trait locus(QTL),quantitative trait nucleotides(QTN),genes of resistance sites,the screening of resistant germplasm resources,and the breeding of new varieties,so as to gain an in-depth understanding of the pathogenesis principle of soybean FLS disease.In order to provide a theoretical basis and technical support for the breeding of soybean FLS disease,the resistance mechanism of soybean FLS disease was analyzed from the molecular level.展开更多
Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sam...Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and...Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and cirrhosis.Although NAFLD is a disease of disordered metabolism,it also involves several immune cell-mediated inflammatory processes,either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process.However,the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation,leaving many open-ended questions.In this review,we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD.We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD.We hope that this review will help guide the development of future NAFLD therapeutics.展开更多
Objective The aim of this study was to assess quality of results of elderly patients with coronary disease after medical or revascularisation therapy. Methods In this study, we enrolled 103 patients aged 75 years or o...Objective The aim of this study was to assess quality of results of elderly patients with coronary disease after medical or revascularisation therapy. Methods In this study, we enrolled 103 patients aged 75 years or older with chronic angina in which 47 patients were assigned coronary angiography and revascularisation and 56 patients with optimised medical therapy. The primary endpoint was quality of life after 6 months, as assessed by questionnaire and the presence of major adverse cardiac events (death, non fatal myocardial infarction, or hospital admission for acute coronary syndrome with or without the need for revascularisation). Results After 6 months follow up, angina severity decreased and measures of quality of life increased in both treatment groups( P <0.05 ); however, these improvements were significantly greater after revascularisation( P <0.01 ). Major adverse cardiac events occurred in 30 ( 53.6% ) of patients in the medical group and 9 ( 19.1% ) in the invasive group ( P <0.01 ).Conclusions Patients aged 75 years or older with angina benefit more from revascularisation than from optimised medical therapy in terms of symptom relief and quality of life. Therefore, these patients should be offered invasive assessment despite their high risk profile followed by revascularisation if feasible.展开更多
基金supported by grants from the Open Research Fund of the Zhejiang Key Laboratory of Precision Psychiatry(2025A2)the Natural Science Foundation of Zhejiang Province(LY23C090002)。
文摘Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.
文摘[Objective]Leaf diseases significantly affect both the yield and quality of tea throughout the year.To address the issue of inadequate segmentation finesse in the current tea spot segmentation models,a novel diagnosis of the severity of tea spots was proposed in this research,designated as MDC-U-Net3+,to enhance segmentation accuracy on the base framework of U-Net3+.[Methods]Multi-scale feature fusion module(MSFFM)was incorporated into the backbone network of U-Net3+to obtain feature information across multiple receptive fields of diseased spots,thereby reducing the loss of features within the encoder.Dual multi-scale attention(DMSA)was incorporated into the skip connection process to mitigate the segmentation boundary ambiguity issue.This integration facilitates the comprehensive fusion of fine-grained and coarse-grained semantic information at full scale.Furthermore,the segmented mask image was subjected to conditional random fields(CRF)to enhance the optimization of the segmentation results[Results and Discussions]The improved model MDC-U-Net3+achieved a mean pixel accuracy(mPA)of 94.92%,accompanied by a mean Intersection over Union(mIoU)ratio of 90.9%.When compared to the mPA and mIoU of U-Net3+,MDC-U-Net3+model showed improvements of 1.85 and 2.12 percentage points,respectively.These results illustrated a more effective segmentation performance than that achieved by other classical semantic segmentation models.[Conclusions]The methodology presented herein could provide data support for automated disease detection and precise medication,consequently reducing the losses associated with tea diseases.
文摘Thrombospondin 4(THBS4;TSP4),a crucial component of the extracellular matrix(ECM),serves as an important regulator of tissue homeostasis and various pathophysiological processes.As a member of the evolutionarily conserved thrombospondin family,THBS4 is a multidomain adhesive glycoprotein characterized by six distinct structural domains that mediate its diverse biological functions.Through dynamic interactions with various ECM components,THBS4 plays pivotal roles in cell adhesion,proliferation,inflammation regulation,and tissue remodeling,establishing it as a key modulator of microenvironmental organization.The transcription and translation of THBS4 gene,as well as the activity of the THBS4 protein,are tightly regulated by multiple signaling pathways and extracellular cues.Positive regulators of THBS4 include transforming growth factorβ(TGF-β),interferonγ(IFNγ),granulocyte-macrophage colony-stimulating factor(GM-CSF),bone morphogenetic proteins(BMP12/13),and other regulatory factors(such as B4GALNT1,ITGA2/ITGB1,PDGFRβ,etc.),which upregulate THBS4 at the mRNA and/or protein level.Conversely,oxidized low-density lipoprotein(OXLDL)acts as a potent negative regulator of THBS4.This intricate regulatory network ensures precise spatial and temporal control of THBS4 expression in response to diverse physiological and pathological stimuli.Functionally,THBS4 acts as a critical signaling hub,influencing multiple downstream pathways essential for cellular behavior and tissue homeostasis.The best-characterized pathways include:(1)the PI3K/AKT/mTOR axis,which THBS4 modulates through both direct and indirect interactions with integrins and growth factor receptors;(2)Wnt/β-catenin signaling,where THBS4 functions as either an activator or inhibitor depending on the cellular context;(3)the suppression of DBET/TRIM69,contributing to its diverse regulatory roles.These signaling connections position THBS4 as a master regulator of cellular responses to microenvironmental changes.Substantial evidence links aberrant THBS4 expression to a range of pathological conditions,including neoplastic diseases,cardiovascular disorders,fibrotic conditions,neurodegenerative diseases,musculoskeletal disorders,and atopic dermatitis.In cancer biology,THBS4 exhibits context-dependent roles,functioning either as a tumor suppressor or promoter depending on the tumor type and microenvironment.In the cardiovascular system,THBS4 contributes to both adaptive remodeling and maladaptive fibrotic responses.Its involvement in fibrotic diseases arises from its ability to regulate ECM deposition and turnover.The diagnostic and therapeutic potential of THBS4 is particularly promising in oncology and cardiovascular medicine.As a biomarker,THBS4 expression patterns correlate significantly with disease progression and patient outcomes.Therapeutically,targeting THBS4-mediated pathways offers novel opportunities for precision medicine approaches,including anti-fibrotic therapies,modulation of the tumor microenvironment,and enhancement of tissue repair.This comprehensive review systematically explores three key aspects of THBS4 research:(1)the fundamental biological functions of THBS4 in ECM organization;(2)its mechanistic involvement in various disease pathologies;(3)its emerging potential as both a diagnostic biomarker and therapeutic target.By integrating recent insights from molecular studies,animal models,and clinical investigations,this review provides a framework for understanding the multifaceted roles of THBS4 in health and disease.The synthesis of current knowledge highlights critical research gaps and future directions for exploring THBS4-targeted interventions across multiple disease contexts.Given its unique position at the intersection of ECM biology and cellular signaling,THBS4 represents a promising frontier for the development of novel diagnostic tools and therapeutic strategies in precision medicine.
文摘Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.
文摘Cardiovascular disease(CVD)remains one of the leading causes of mortality among adults globally,with continuously rising morbidity and mortality rates.Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression,involving multifaceted mechanisms such as altered substrate utilization,mitochondrial structural and functional dysfunction,and impaired ATP synthesis and transport.In recent years,the potential role of peroxisome proliferator-activated receptors(PPARs)in cardiovascular diseases has garnered significant attention,particularly peroxisome proliferator-activated receptor alpha(PPARα),which is recognized as a highly promising therapeutic target for CVD.PPARαregulates cardiovascular physiological and pathological processes through fatty acid metabolism.As a ligand-activated receptor within the nuclear hormone receptor family,PPARαis highly expressed in multiple organs,including skeletal muscle,liver,intestine,kidney,and heart,where it governs the metabolism of diverse substrates.Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions,PPARαexerts its cardioprotective effects through multiple pathways:modulating lipid metabolism,participating in cardiac energy metabolism,enhancing insulin sensitivity,suppressing inflammatory responses,improving vascular endothelial function,and inhibiting smooth muscle cell proliferation and migration.These mechanisms collectively reduce the risk of cardiovascular disease development.Thus,PPARαplays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation,anti-inflammatory actions,and anti-apoptotic effects.PPARαis activated by binding to natural or synthetic lipophilic ligands,including endogenous fatty acids and their derivatives(e.g.,linoleic acid,oleic acid,and arachidonic acid)as well as synthetic peroxisome proliferators.Upon ligand binding,PPARαactivates the nuclear receptor retinoid X receptor(RXR),forming a PPARα-RXR heterodimer.This heterodimer,in conjunction with coactivators,undergoes further activation and subsequently binds to peroxisome proliferator response elements(PPREs),thereby regulating the transcription of target genes critical for lipid and glucose homeostasis.Key genes include fatty acid translocase(FAT/CD36),diacylglycerol acyltransferase(DGAT),carnitine palmitoyltransferase I(CPT1),and glucose transporter(GLUT),which are primarily involved in fatty acid uptake,storage,oxidation,and glucose utilization processes.Advancing research on PPARαas a therapeutic target for cardiovascular diseases has underscored its growing clinical significance.Currently,PPARαactivators/agonists,such as fibrates(e.g.,fenofibrate and bezafibrate)and thiazolidinediones,have been extensively studied in clinical trials for CVD prevention.Traditional PPARαagonists,including fenofibrate and bezafibrate,are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol(HDL-C)levels.These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα,and their cardioprotective effects have been validated in numerous clinical studies.Recent research highlights that fibrates improve insulin resistance,regulate lipid metabolism,correct energy metabolism imbalances,and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells,thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure.Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications,activating PPARαmay serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy,atherosclerosis,ischemic cardiomyopathy,myocardial infarction,diabetic cardiomyopathy,and heart failure.This review comprehensively examines the regulatory roles of PPARαin cardiovascular diseases and evaluates its clinical application value,aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.
文摘Parkinson’s disease(PD)is a common neurodegenerative disorder with profound impact on patients’quality of life and long-term health,and early detection and intervention are particularly critical.In recent years,the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD.In this paper,we systematically evaluated potential biomarkers,including proteins,metabolites,epigenetic markers,and exosomes,in the peripheral blood of PD patients.Protein markers are one of the main directions of biomarker research in PD.In particular,α‑synuclein and its phosphorylated form play a key role in the pathological process of PD.It has been shown that aggregation ofα-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD.In terms of metabolites,uric acid,as a metabolite,plays an important role in oxidative stress and neuroprotection in PD.It has been found that changes in uric acid levels may be associated with the onset and progression of PD,showing its potential as an early diagnostic marker.Epigenetic markers,such as DNA methylation modifications and miRNAs,have also attracted much attention in Parkinson’s disease research.Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease,providing new research perspectives for the early diagnosis of PD.In addition,exosomes,as a potential biomarker carrier for PD,are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation.Studies have shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide a new breakthrough for early diagnosis.It has been shown that exosomes may play an important role in the pathogenesis of PD,and their detection in blood may provide new breakthroughs in early diagnosis.In summary,through in-depth evaluation of biomarkers in the peripheral blood of PD patients,this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms.Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.
文摘Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.
文摘Objective:To evaluate the predictive value of the neutrophil⁃to⁃lymphocyte ratio(NLR)and the systemic immune⁃inflammation index(SII)in predicting patients with anti⁃melanoma differentiation⁃associated gene 5⁃positive(anti⁃MDA5+)dermatomyositis(DM)develop into the rapidly progressive interstitial lung disease(RPILD).Methods:We retrospectively analyzed the clinical and laboratory data of 124 anti⁃MDA5+DM patients from the First Affiliated Hospital of Nanjing Medical University between March 2019 and September 2023.We identified independent risk factors associated with the development and mortality of RPILD with the Cox regression analysis,and determined the optimal cut⁃off values for predicting adverse outcomes with the receiver operating characteristic(ROC)curve analysis.Results:Among the 124 patients,36 patients(29.03%)developed RPILD,and 39 patients(31.45%)died during the follow⁃up period.The results of multivariate Cox regression analysis showed that the elevated NLR was an independent risk factor for RPILD development,while the elevated SII expression was independently associated with the increased mortality of RPILD.Based on the ROC curve analysis,NLR>6.12 was a predictor for RPILD,and SII>875.79 was associated with increased mortality risk of RPILD.Conclusion:Both NLR and SII are accessible,cost⁃effective,and reliable prognostic indicators for the prognosis of patients with anti⁃MDA5^(+)DM,providing a valuable guidance for clinical management and risk stratification of the disease.
基金supported by the National Natural Science Foundation,China(82103704).
文摘Currently,research on N^(6)-methyladenine(m^(6)A)is extensive in the field of oncology,while studies involving m^(6)A and skin diseases remain relatively limited.Based on existing reports,we searched PubMed and Web of Science for literature related to m^(6)A and dermatological conditions.Analysis of citation counts and journal impact factors revealed a significant upward trend in the volume of m^(6)A-related research.Term frequency analysis of titles and abstracts indicated that studies mainly focus on skin tumors and inflammatory or immune-related skin diseases,particularly melanoma,psoriasis,and skin development.Transcriptomic data from the Gene Expression Omnibus(GEO)were analyzed,revealing differential expression of m^(6)A-related genes in 4 types of skin tumors(including squamous cell carcinoma and basal cell carcinoma)as well as in inflammatory skin diseases such as psoriasis and atopic dermatitis,and potential mechanisms of action were also explored.Findings suggest that m^(6)A modifications exhibit heterogeneity between neoplastic and nonneoplastic skin diseases.However,the regulatory mechanisms of m^(6)A dynamic modifications on key genes involved in dermatological disorders remain unclear and warrant further investigation.
基金supported by National Natural Science Foundation of China(32201752)Xinjiang Tianchi Talents Program (TCYC2023TP02)Key Project of the Natural Science Foundation of Xinjiang Production and Construction Corps (2024DA001)
文摘Verticillium wilt,caused by the infamous pathogen Verticillium dahliae,presents a primary constraint on cotton cul-tivation worldwide.The complexity of disease resistance in cotton and the largely unexplored interaction dynamics between the cotton plant host and V.dahliae pathogen pose a crucial predicament for effectively managing cotton Verticillium wilt.Nevertheless,the most cost-effective approach to controlling this disease involves breeding and cul-tivating resistant cotton varieties,demanding a meticulous analysis of the mechanisms underlying cotton’s resistance to Verticillium wilt and the identification of pivotal genes.These aspects constitute focal points in disease-resistance breeding programs.In this review,we comprehensively discuss genetic inheritance associated with Verticillium wilt resistance in cotton,the advancements in molecular markers for disease resistance,the functional investiga-tion of resistance genes in cotton,the analysis of pathogenicity genes in V.dahliae,as well as the intricate interplay between cotton and this fungus.Moreover,we delve into the future prospects of cutting-edge research on cotton Verticillium wilt,aiming to proffer valuable insights for the effective management of this devastating fungus.
基金Supported by the 14th Five-Year National Key Research and Development Program(2021YFD1201103–01–05)the National Natural Science Foundation of China(32301819)the Cooperation Project of Research and Development Center between Wudalianchi Government and Northeast Agricultural University.
文摘Soybean frogeye leaf spot(FLS)disease is a worldwide disease caused by Cercospora sojina Hara.It is one of the major diseases suffered by soybean during the growth cycle,which seriously damages the yield and seed quality of soybean.The current resistant varieties are difficult to meet the production demand.The breeders have identified 50 different physiological small species and discussed the physiological and biochemical characteristics of soybean resistance to FLS.In soybean disease resistance breeding,resistance resources are screened for the main physiological races in different countries,resistance materials are created,more than 100 genome regions associated with resistance are located,and 12 resistance-related genes are identified.In order to promote the research of soybean disease resistance breeding,this paper expounded and analyzed the pathogenesis characteristics of soybean FLS,the division of races,the physiological and biochemical mechanism of soybean resistance to FLS disease,quantitative trait locus(QTL),quantitative trait nucleotides(QTN),genes of resistance sites,the screening of resistant germplasm resources,and the breeding of new varieties,so as to gain an in-depth understanding of the pathogenesis principle of soybean FLS disease.In order to provide a theoretical basis and technical support for the breeding of soybean FLS disease,the resistance mechanism of soybean FLS disease was analyzed from the molecular level.
基金This work was supported by the National Natural Science Foundation (82273506,82273508)the Hunan Provincial Health Commission Scientific Research Plan Project (D202304128334),China。
文摘Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and cirrhosis.Although NAFLD is a disease of disordered metabolism,it also involves several immune cell-mediated inflammatory processes,either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process.However,the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation,leaving many open-ended questions.In this review,we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD.We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD.We hope that this review will help guide the development of future NAFLD therapeutics.
文摘Objective The aim of this study was to assess quality of results of elderly patients with coronary disease after medical or revascularisation therapy. Methods In this study, we enrolled 103 patients aged 75 years or older with chronic angina in which 47 patients were assigned coronary angiography and revascularisation and 56 patients with optimised medical therapy. The primary endpoint was quality of life after 6 months, as assessed by questionnaire and the presence of major adverse cardiac events (death, non fatal myocardial infarction, or hospital admission for acute coronary syndrome with or without the need for revascularisation). Results After 6 months follow up, angina severity decreased and measures of quality of life increased in both treatment groups( P <0.05 ); however, these improvements were significantly greater after revascularisation( P <0.01 ). Major adverse cardiac events occurred in 30 ( 53.6% ) of patients in the medical group and 9 ( 19.1% ) in the invasive group ( P <0.01 ).Conclusions Patients aged 75 years or older with angina benefit more from revascularisation than from optimised medical therapy in terms of symptom relief and quality of life. Therefore, these patients should be offered invasive assessment despite their high risk profile followed by revascularisation if feasible.
