BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and...BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and geographic features.Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis(JIA)allows us to shape the work of the pediatric rheumatology service in the region correctly,and optimize the healthcare system and the need for medica-tions.AIM To describe the epidemiological,demographic,clinical,and laboratory characteristics of children with JIA in the RS(Y)and evaluate the main outcomes.METHODS This retrospective cohort study assessed all the data from the medical histories of the patients(n=225)diagnosed with JIA(2016-2023)in the Cardiorheumatology Department of the M.E.Nikolaev National Center of Medicine.Pearson'sχ²test,Fisher's exact test,Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.RESULTS The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children,respectively.The prevalence of JIA among boys and girls in Sakha was similar,unlike in Russians,where the number of girls predominated.The JIA categories were as follows:(1)Systemic arthritis:3.5%;(2)Oligoarthritis(persistent and extended):33.8%;(3)Rheumatoid factor(RF)(+)polyarthritis:0.9%;(4)RF(-)polyarthritis:14.7%;(5)Enthesitis-related arthritis(ERA):44%;and(6)Psoriatic arthritis:3.1%.Prevalence of the ERA category was 4.4 times higher in Sakha children,but the prevalence of systemic arthritis was 2.9 times lower compared to Russians(P=0.0005).The frequency of uveitis was 10.2%,and the frequency of human leukocyte antigen(HLA)B27 was 39.6%in JIA children.Biologic treatment was received by 40.4%of JIA children and 45.3%achieved remission.CONCLUSION Higher JIA prevalence,male and ERA predominance,related to a higher frequency of HLA B27 are typical in RS(Y).These data might improve the pediatric rheumatology health service.展开更多
Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articul...Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.展开更多
The combination of Daphnes Cortex(DC)and Liquorice Root(LR),two traditional Chinese medicinal herbs,has shown significant therapeutic effects on rheumatoid arthritis(RA),but its synergistic mechanism of action remains...The combination of Daphnes Cortex(DC)and Liquorice Root(LR),two traditional Chinese medicinal herbs,has shown significant therapeutic effects on rheumatoid arthritis(RA),but its synergistic mechanism of action remains to be elucidated.Employing a network pharmacology and molecular docking approach,this study systematically investigated the synergistic mechanism of the herb pair DC and LR in RA treatment.Active components and their corresponding targets were retrieved from the TCMSP database and relevant literature,and RA-related targets were collected from established disease databases.A total of 73 overlapping targets between DC-LR and RA were identified,among which core targets such as AKT1,TNF,and CASP3 were highlighted.GO and KEGG enrichment analyses revealed that these targets are involved in biological processes such as oxidative stress response and cell migration,and are significantly enriched in key pathways including HIF-1,TNF,and PI3K-Akt signaling pathways.Compatibility analysis further revealed that the combination of DC and LR may enhance therapeutic effects through synergistic regulation of shared targets and complementary modulation of upstream and downstream pathway components.Molecular docking confirmed strong binding affinities between core active components and key targets.This study provides a multi-dimensional“component-target-pathway”perspective on the potential synergistic anti-RA mechanism of the DC-LR herb pair,offering a theoretical basis for further experimental validation and clinical application.展开更多
Rheumatoid arthritis(RA)patients face significant psychological challenges alongside physical symptoms,necessitating a comprehensive understanding of how psychological vulnerability and adaptation patterns evolve thro...Rheumatoid arthritis(RA)patients face significant psychological challenges alongside physical symptoms,necessitating a comprehensive understanding of how psychological vulnerability and adaptation patterns evolve throughout the disease course.This review examined 95 studies(2000-2025)from PubMed,Web of Science,and CNKI databases including longitudinal cohorts,randomized controlled trials,and mixed-methods research,to characterize the complex interplay between biological,psychological,and social factors affecting RA patients’mental health.Findings revealed three distinct vulnerability trajectories(45%persistently low,30%fluctuating improvement,25%persistently high)and four adaptation stages,with critical intervention periods occurring 3-6 months postdiagnosis and during disease flares.Multiple factors significantly influence psychological outcomes,including gender(females showing 1.8-fold increased risk),age(younger patients experiencing 42%higher vulnerability),pain intensity,inflammatory markers,and neuroendocrine dysregulation(48%showing cortisol rhythm disruption).Early psychological intervention(within 3 months of diagnosis)demonstrated robust benefits,reducing depression incidence by 42%with effects persisting 24-36 months,while different modalities showed complementary advantages:Cognitive behavioral therapy for depression(Cohen’s d=0.68),mindfulness for pain acceptance(38%improvement),and peer support for meaning reconstruction(25.6%increase).These findings underscore the importance of integrating routine psychological assessment into standard RA care,developing stage-appropriate interventions,and advancing research toward personalized biopsychosocial approaches that address the dynamic psychological dimensions of the disease.展开更多
Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,t...Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.展开更多
Arthritis,encompassing osteoarthritis(OA),rheumatoid arthritis(RA),and gouty arthritis(GA),is a prevalent inflammatory disease that significantly impacts quality of life.Natural products(NPs),derived from animals,plan...Arthritis,encompassing osteoarthritis(OA),rheumatoid arthritis(RA),and gouty arthritis(GA),is a prevalent inflammatory disease that significantly impacts quality of life.Natural products(NPs),derived from animals,plants,marine organisms,and microorganisms,have demonstrated beneficial effects in arthritis treatment both domestically and internationally.These natural compounds offer advantages in drug discovery due to their skeletal diversity,structural complexity,and multi-effect,multi-target,and low-toxicity properties compared to conventional small-molecule medicines.However,unclear mechanisms have hindered the development and clinical application of NPs.This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment,emphasizing key NPs with therapeutic effects on OA,RA,and GA.It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis.Furthermore,this review provides insights into the future prospects of NP research in this field,which is crucial for advancing NP-based arthritis treatments.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19...Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.展开更多
Rheumatoid arthritis(RA)is a prevalent and debilitating inflammatory disease that significantly impairs functional capacity and quality of life.RA accelerates musculoskeletal aging,leading to complications such as mus...Rheumatoid arthritis(RA)is a prevalent and debilitating inflammatory disease that significantly impairs functional capacity and quality of life.RA accelerates musculoskeletal aging,leading to complications such as muscle degeneration and sarcopenia.Recent research has identified myopenia as a condition of significant muscle loss associated with illness,distinct from the muscle wasting seen in other chronic diseases like cancer cachexia or heart failure.In RA,myopenia is characterized by muscle depletion without concurrent significant fat loss,and it can affect individuals of all ages.While inflammation plays a central role,it is not the sole factor contributing to the high incidence of muscle wasting in RA.In subsequent discussions,secondary sarcopenia will be considered alongside myopenia,as both involve muscle wasting decline primarily due to disease.This review summarizes recent findings on the impact of RA-related myopenia and secondary sarcopenia on functional capacity,explores its underlying mechanisms,and discusses contemporary strategies to mitigate the process of musculoskeletal aging in RA patients.展开更多
Itaconate,a macrophage-specific anti-inflammatory metabolite,has recently emerged as a critical regulator in rheumatoid arthritis pathogenesis.We found that itaconate is a TNF-αresponsive metabolite significantly ele...Itaconate,a macrophage-specific anti-inflammatory metabolite,has recently emerged as a critical regulator in rheumatoid arthritis pathogenesis.We found that itaconate is a TNF-αresponsive metabolite significantly elevated in the serum and synovial fluid of rheumatoid arthritis patients and we demonstrated that itaconate is primarily produced by inflammatory macrophages rather than osteoclasts or osteoblasts.In TNF-transgenic and Irg1−/−hybrid mice,a more severe bone destruction phenotype was observed.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflamm...Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflammatory mediators in this process is well-established,the contribution of non-inflammatory regulators in SFs to joint pathology remains poorly understood.In this study,we investigated the non-inflammatory role of SFs in RA using a co-culture model,and found that SFs from RA patients promote apoptosis of human chondrocytes.Mechanistic investigations reveal that SFs can secrete small extracellular vesicles(sEVs),which are taken up by chondrocytes and induce chondrocyte apoptosis in both normal chondrocytes and chondrocytes from patients with RA.sEV-derived miRNA 15-29148 are identified as key signaling molecules mediating the apoptosis effects of chondrocytes.Further studies reveal that SF-derived miRNA 15-29148 targeting CIAPIN1 results in increased chondrocyte apoptosis.We further demonstrate that SF-derived miRNA 15-29148 is transferred to chondrocytes,exacerbating cartilage damage in vivo.Moreover,chondrocyte-specific aptamer-modified polyamidoamine nanoparticles not only ameliorated RA but also prevented its onset.This study suggests that,in RA,the secretion of specific sEV-miRNAs from SFs plays a crucial role in promoting chondrocyte apoptosis,potentially through non-inflammatory regulation,and that sEV-miRNA inhibition in SFs may represent an early preventive treatment strategy for cartilage degradation in RA.展开更多
Post-traumatic osteoarthritis(PTOA)is a complex and painful problem in the foot and ankle.Ninety percent of osteoarthritis cases in the foot and ankle can be classified as post-traumatic.PTOA can affect any of the 33 ...Post-traumatic osteoarthritis(PTOA)is a complex and painful problem in the foot and ankle.Ninety percent of osteoarthritis cases in the foot and ankle can be classified as post-traumatic.PTOA can affect any of the 33 joints in the foot and the ankle.Distraction arthroplasty is a method for treatment of early arthritic joints without fusing or replacing them and its effectiveness has been well documented.The purpose of this case series is to present our successful experiences and positive results using distraction arthroplasty to treat PTOA in the ankle,subtalar,first metatarsophalangeal,and second tarsometatarsal joints,and to present distraction arthroplasty as a viable alternative to invasive joint sacrificing procedures such as arthrodesis or arthroplasty.Distraction Arthroplasty effectively and safely treats PTOA and improves the stability of joints in the Foot and Ankle.Additionally,the use of bone marrow aspirate concentrate as an adjuvant can improve the long-term functional and structural outcomes of the joint,and can prolong the need for further,more aggressive surgical interventions such as fusion or arthroplasty.展开更多
Objective To reveal the therapeutic effects of moxibustion in collagen-induced arthritis(CIA)rat models using the combined analysis of plasma and synovial membrane lipidomic profil-ing and to enhance the understanding...Objective To reveal the therapeutic effects of moxibustion in collagen-induced arthritis(CIA)rat models using the combined analysis of plasma and synovial membrane lipidomic profil-ing and to enhance the understanding of how moxibustion affects lipid metabolism in rheumatoid arthritis(RA).Methods A total of 32 male Sprague-Dawley(SD)rats were randomly assigned to four groups:control,moxibustion control(MC),model,and moxibustion model(MM)groups,with 8 rats in each group.CIA was induced in SD rats by two immunizations.The paw volume was mea-sured before the induction of CIA.Following induction,after assessing paw volume and arthritis index(AI)scores,the MC and MM groups received treatment at bilateral Shenshu(BL23)and Zusanli(ST36)acupoints for 10 min per acupoint.The intervention included three treatment courses,each spanning 6 d and followed by a 1-d interval.Paw volume and AI scores were assessed after each treatment course.After the completion of the three treatment courses,serum,plasma,synovial tissue,and ankle joint samples were collected.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-αin serum.Hematoxylin and eosin(HE)staining was per-formed for histopathological examination of the ankle joint tissues.Meanwhile,ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS)was utilized to analyze the plasma and synovial tissue sam-ples.In addition,multivariate statistical analysis was performed to identify differential lipid metabolites,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was applied to explore metabolic pathways modulated by moxibustion therapy.Results No significant difference in hind paw volume and AI scores was observed among the groups(P>0.05).After CIA induction,model group showed increased hind paw volume and AI scores compared with control group(P<0.05),which were significantly reduced after mox-ibustion treatment in MM group compared with model group(P<0.05).The levels of IL-6 and TNF-αwere significantly higher in model and MM groups compared with control group(P<0.05),but were lower in MM group than those in model group(P<0.05).Histopathologi-cal analysis showed improved cartilage and reduced inflammation in MM group.A total of 33 differential lipid metabolites in the plasma and 24 in the synovial membranes of CIA rat mod-els were identified when compared with control group.Among these lipid metabolites,31 in the plasma and all 24 in the synovial membranes were regulated by moxibustion treatment.Pathological analysis revealed upregulation of diacylglycerol(DG)and fatty acid(FA)levels,alongside downregulation of lysophosphatidylcholine(LPC),phosphatidylcholine(PC),and phosphatidylethanolamine(PE).Under physiological conditions,the treatment specifically reduced LPC and PC levels.Pathway enrichment analysis revealed that moxibustion predom-inantly affectedα-linolenic acid,glycerophospholipid,and sphingolipid metabolism under pathological conditions.Under physiological conditions,the regulation was centered aroundα-linolenic acid and glycerophospholipid metabolism.Conclusion The RA rat models exhibited significant lipid metabolic disturbances.Moxibus-tion alleviated paw swelling,reduced AI scores,modulated inflammatory cytokine levels,and partially corrected the altered levels of multiple lipid metabolites.The potential metabolic pathways implicated in the regulation of lipid metabolism under both physiological and pathological conditions includeα-linolenic acid,glycerophospholipid,and sphingolipid metabolism.展开更多
Rheumatoid arthritis(RA)is a common chronic autoimmune disease characterized by joint pain,swelling and dysfunction[1].According to epidemiologic statistics,the incidence of RA is 1%–2%,and in severe cases,it can dev...Rheumatoid arthritis(RA)is a common chronic autoimmune disease characterized by joint pain,swelling and dysfunction[1].According to epidemiologic statistics,the incidence of RA is 1%–2%,and in severe cases,it can develop into joint deformity and disability,which brings a heavy burden to the family and society[2].However,the pathogenesis of RA is complex and involves multiple cellular interactions,which increases the difficulty of curing RA.Current therapeutic options,such as disease-modifying antirheumatic drugs,non-steroidal anti-inflammatory drugs,and biologics,still face the challenge of relapse after drug discontinuation[3,4].Therefore,the pathogenesis of RA needs to be analyzed in depth to break through the existing therapeutic bottlenecks and promote the iterative innovation of individualized diagnosis and treatment.展开更多
BACKGROUND Juvenile arthritis damage index(JADI)is a tool that measures the degree of aggressiveness of the juvenile idiopathic arthritis(JIA)course and assesses articular[JADI-articular damage(JADI-A)]and extraarticu...BACKGROUND Juvenile arthritis damage index(JADI)is a tool that measures the degree of aggressiveness of the juvenile idiopathic arthritis(JIA)course and assesses articular[JADI-articular damage(JADI-A)]and extraarticular[JADI-extraarticular damage(JADI-E)]damage.While aggressive JIA often requires early bio-logic disease-modified antirheumatic drugs(bDMARDs),the utility of JADI as a predictor of treatment response remains underexplored.AIM To evaluate the potential of JADI as a predictor of bDMARD treatment response in JIA patients.METHODS This prospective study included 112 highly active non-systemic JIA biologic-naïve patients with a mean age of 12.2±4.6 years and a median disease duration of 2.5(interquartile range:1-5)years.Their clinical and radiological assessment,juvenile arthritis disease activity score 71,JADI-A,and JADI-E,were evaluated twice:Before the biologic initiation(baseline)and 12 months after(end of study).At baseline,50%had any damage,with 43%with articular damage and 23%with extraarticular damage.RESULTS During the study,JADI-A/JADI-E improved(33.9%/9.8%),worsened(8.9%/5.4%),or remained unchanged(57.1%/84.8%).Patients with baseline damage had higher markers of JIA activity:Polyarticular course,earlier onset age,ANA-positivity,and more active joints.Patients without initial structural damage(JADI“-”)were more likely(odds ratio=3.8,95%confidence interval:1.6-9.0,P<0.004)to achieve a low degree of activity or remission(46.2%),while on biological therapy,their scores were comparable to JADI-positive(18.3%).Pre-biological joint damage according to the JADI-A index(P=0.003),wrist(P=0.035),elbow(P=0.027),cervical spine limitation of motion(P=0.051),and erosions confirmed by magnetic resonance imaging(P=0.002),were associated with poor response to biological treatment and follow-up JIA activity.CONCLUSION Baseline structural damage in JIA is associated with diminished bDMARDs efficacy,increased disability,and shorter remission duration.JADI enhances conventional clinical risk stratification by facilitating timely initiation of bDMARDs,adherence to treat-to-target strategy and tailored patient care.展开更多
Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples...Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples from patients with different pathological processes were collected, and the correlations between the subsets of FLSs and STMs and pathological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell assays, CCK- 8 assays and cell coculture were used to assess cell proliferation, migration and secretion of inflammatory factors. A collagen- induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytometry, micro- CT and staining. Results : Unique subsets of FLSs and STMs, namely, FAPα ^(+)THY1 − FLSs, FAPα ^(+)THY1 ^(+)FLSs, and MerTK ^(pos) TREM2 ^(high) STMs, were identified in synovial tissues from RA patients. The number of MerTK ^(pos) TREM2 ^(high) STMs was negatively correlated with the degree of damage in RA, while the number of FAPα ^(+)THY1 − FLSs was positively correlated with damage. On the one hand, emodin promoted the aggregation of MerTKposTREM2high STMs. Moreover, MerTK pos TREM2 high STM- mediated secretion of exosomes was promoted, which can inhibit the secretion of pro- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs and promote the secretion of anti- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs, thereby inhibiting FAPα ^(+)THY1 − FLS proliferation and migration, improving the local immune microenvironment, and inhibiting RA damage. Conclusion : Emodin was shown to regulate the aggregation of STM subsets and exosome secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA patients, suggesting that it has important clinical value.展开更多
Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal a...Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.展开更多
Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine...Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine preparation used to treat RA.ZF may cause liver injury.In this study,we aimed to develop a prediction model for abnormal liver function caused by ZF.Methods This retrospective study collected data from multiple centers from January 2018 to April 2023.Abnormal liver function was set as the target variable according to the alanine transaminase(ALT)level.Features were screened through univariate analysis and sequential forward selection for modeling.Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data.Results This study included 1,913 eligible patients.The LightGBM model exhibited the best performance(accuracy=0.96)out of the 10 learning models.The predictive metrics of the LightGBM model were as follows:precision=0.99,recall rate=0.97,F1_score=0.98,area under the curve(AUC)=0.98,sensitivity=0.97 and specificity=0.85 for predicting ALT<40 U/L;precision=0.60,recall rate=0.83,F1_score=0.70,AUC=0.98,sensitivity=0.83 and specificity=0.97 for predicting 40≤ALT<80 U/L;and precision=0.83,recall rate=0.63,F1_score=0.71,AUC=0.97,sensitivity=0.63 and specificity=1.00 for predicting ALT≥80 U/L.ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels,the combination of TNF-αinhibitors,JAK inhibitors,methotrexate+nonsteroidal anti-inflammatory drugs,leflunomide,smoking,older age,and females in middle-age(45-65 years old).Conclusion This study developed a model for predicting ZF-induced abnormal liver function,which may help improve the safety of integrated administration of ZF and Western medicine.展开更多
Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint def...Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint deformity and dysfunction in severe cases.The pathologic development of RA involves complex interactions of multiple biomarkers,and detecting a single biomarker may produce falsepositive results due to other confounding factors.Therefore,fluorescent probes that can detect multiple biomarkers simultaneously are crucial for precise RA diagnosis.Peroxynitrite(ONOO^(-)) and viscosity are inflammation-related factors in cells.In this study,we developed a dual responsive near-infrared fluorescent probe,YLS,for ONOO^(-) and viscosity.The probe features dual-channel turn-on fluorescence responses at 625 and 760 nm upon the presence of ONOO^(-) and viscosity,respectively.Supported by YLS,we found that during RA pathology,lymphocyte infiltration not only increases the concentration of proteins in the joint fluid resulting in elevated viscosity;at the same time,the overproduction of ONOO^(-) exacerbates oxidative stress and inflammatory responses.This multiparameter assay is expected to improve the diagnostic accuracy of the early stages of RA,thus providing a scientific basis for early intervention and personalized treatment.展开更多
BACKGROUND This study investigates the impact of type 2 diabetes mellitus(T2DM)on the risk of interstitial lung disease(ILD)and its subtypes in patients with rheumatoid arthritis(RA).RA is often complicated by ILD.T2D...BACKGROUND This study investigates the impact of type 2 diabetes mellitus(T2DM)on the risk of interstitial lung disease(ILD)and its subtypes in patients with rheumatoid arthritis(RA).RA is often complicated by ILD.T2DM has systemic proinflam-matory effects,but its impact on RA-related ILD is unclear.This research aims to elucidate the interplay between these conditions to inform clinical management and patient care strategies.AIM To determine if RA patients with T2DM have a higher occurrence of ILD compar-ed to RA patients without T2DM.METHODS We conducted a retrospective cohort study using the 2019-2020 National Inpa-tient Sample.Adult RA patients with and without T2DM were identified via International Classification of Diseases,10th Revision(ICD-10)codes.Propensity score matching(1:1)balanced 15+confounders.Logistic regression assessed the association of T2DM with ILD(overall and by subtype)and secondary outcomes(acute respiratory distress syndrome,pneumothorax,pleural effusion,pulmonary hypertension).Missing data were excluded.ILD subtypes were included based on ICD-10 codes and case count.RESULTS Among 199380 RA inpatients,ILD was more common in those with T2DM(2.25%)vs without(1.11%).After matching(n=121046),ILD remained higher in RA+T2DM[odds ratio(OR)=2.02,95%CI:1.84-2.22,P<0.001],with an absolute risk increase of about 1.14%.T2DM was associated with higher odds of ILD subtypes including usual interstitial pneumonia(OR=3.20)and non-specific interstitial pneumonia(OR=3.50).Other subtypes showed elevated ORs;eosinophilic pneumonia showed an inverse association(OR=0.23).PAH and pneumo-thorax were also more common in RA+T2DM(OR=1.40 and 1.85,respectively).Acute respiratory distress syn-drome and pleural effusion rates did not differ by T2DM status.Rare subtype findings should be interpreted cautiously.CONCLUSION T2DM increases ILD risk in RA and is linked to higher rates of pulmonary hypertension and pneumothorax,suggesting a role in exacerbating RA-related lung complications.展开更多
Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate ...Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis.Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling,improved body weights,and attenuated pathological changes in joints of rats with adjuvant-induced arthritis.Additionally,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and IL-1β in the serum and ankle joints were reduced.Bioinformatics analysis,along with the spleen index and measurements of IL-17 and IL-10 levels,suggested a potential relationship between AS and Th17 cells under arthritic conditions.In vitro,AS was shown to block Th17 cell differentiation,as evidenced by the reduced percentages of CD4^(+)IL-17A^(+)T cells and decreased expression levels of RORγt,IL-17A,IL-17F,IL-21,and IL-22,without affecting the cell viability and apoptosis.This effect was attributed to the limited glycolysis,as indicated by metabolomics analysis,reduced glucose uptake,and p H measurements.Further investigation revealed that AS might bind to hexokinase2(HK2)to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase(GAPDH)or pyruvate kinase M2(PKM2),and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation.Furthermore,AS impaired the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signals in vivo and in vitro,which was abolished by the addition of lactate.In conclusion,AS significantly improved adjuvant-induced arthritis(AIA)in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.展开更多
文摘BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and geographic features.Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis(JIA)allows us to shape the work of the pediatric rheumatology service in the region correctly,and optimize the healthcare system and the need for medica-tions.AIM To describe the epidemiological,demographic,clinical,and laboratory characteristics of children with JIA in the RS(Y)and evaluate the main outcomes.METHODS This retrospective cohort study assessed all the data from the medical histories of the patients(n=225)diagnosed with JIA(2016-2023)in the Cardiorheumatology Department of the M.E.Nikolaev National Center of Medicine.Pearson'sχ²test,Fisher's exact test,Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.RESULTS The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children,respectively.The prevalence of JIA among boys and girls in Sakha was similar,unlike in Russians,where the number of girls predominated.The JIA categories were as follows:(1)Systemic arthritis:3.5%;(2)Oligoarthritis(persistent and extended):33.8%;(3)Rheumatoid factor(RF)(+)polyarthritis:0.9%;(4)RF(-)polyarthritis:14.7%;(5)Enthesitis-related arthritis(ERA):44%;and(6)Psoriatic arthritis:3.1%.Prevalence of the ERA category was 4.4 times higher in Sakha children,but the prevalence of systemic arthritis was 2.9 times lower compared to Russians(P=0.0005).The frequency of uveitis was 10.2%,and the frequency of human leukocyte antigen(HLA)B27 was 39.6%in JIA children.Biologic treatment was received by 40.4%of JIA children and 45.3%achieved remission.CONCLUSION Higher JIA prevalence,male and ERA predominance,related to a higher frequency of HLA B27 are typical in RS(Y).These data might improve the pediatric rheumatology health service.
文摘Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.
基金supported by National Training Program of Innovation and Entrepreneurship for Undergraduates(202510163044).
文摘The combination of Daphnes Cortex(DC)and Liquorice Root(LR),two traditional Chinese medicinal herbs,has shown significant therapeutic effects on rheumatoid arthritis(RA),but its synergistic mechanism of action remains to be elucidated.Employing a network pharmacology and molecular docking approach,this study systematically investigated the synergistic mechanism of the herb pair DC and LR in RA treatment.Active components and their corresponding targets were retrieved from the TCMSP database and relevant literature,and RA-related targets were collected from established disease databases.A total of 73 overlapping targets between DC-LR and RA were identified,among which core targets such as AKT1,TNF,and CASP3 were highlighted.GO and KEGG enrichment analyses revealed that these targets are involved in biological processes such as oxidative stress response and cell migration,and are significantly enriched in key pathways including HIF-1,TNF,and PI3K-Akt signaling pathways.Compatibility analysis further revealed that the combination of DC and LR may enhance therapeutic effects through synergistic regulation of shared targets and complementary modulation of upstream and downstream pathway components.Molecular docking confirmed strong binding affinities between core active components and key targets.This study provides a multi-dimensional“component-target-pathway”perspective on the potential synergistic anti-RA mechanism of the DC-LR herb pair,offering a theoretical basis for further experimental validation and clinical application.
基金Supported by Chongqing Health Commission and Chongqing Science and Technology Bureau,No.2023MSXM182。
文摘Rheumatoid arthritis(RA)patients face significant psychological challenges alongside physical symptoms,necessitating a comprehensive understanding of how psychological vulnerability and adaptation patterns evolve throughout the disease course.This review examined 95 studies(2000-2025)from PubMed,Web of Science,and CNKI databases including longitudinal cohorts,randomized controlled trials,and mixed-methods research,to characterize the complex interplay between biological,psychological,and social factors affecting RA patients’mental health.Findings revealed three distinct vulnerability trajectories(45%persistently low,30%fluctuating improvement,25%persistently high)and four adaptation stages,with critical intervention periods occurring 3-6 months postdiagnosis and during disease flares.Multiple factors significantly influence psychological outcomes,including gender(females showing 1.8-fold increased risk),age(younger patients experiencing 42%higher vulnerability),pain intensity,inflammatory markers,and neuroendocrine dysregulation(48%showing cortisol rhythm disruption).Early psychological intervention(within 3 months of diagnosis)demonstrated robust benefits,reducing depression incidence by 42%with effects persisting 24-36 months,while different modalities showed complementary advantages:Cognitive behavioral therapy for depression(Cohen’s d=0.68),mindfulness for pain acceptance(38%improvement),and peer support for meaning reconstruction(25.6%increase).These findings underscore the importance of integrating routine psychological assessment into standard RA care,developing stage-appropriate interventions,and advancing research toward personalized biopsychosocial approaches that address the dynamic psychological dimensions of the disease.
基金the National Natural Science Foundation of China(82204935)the construction project of Zhao Feng National Old Pharmacist Inheritance Studio of State Administration of Traditional Chinese Medicine(National Traditional Chinese Medicine Education Letter[2024]255)+1 种基金the open project of the Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine in Shaanxi Province(KF202302)the project of Xi’an Municipal Bureau of Science and Technology(23YXYJ0042)for financial support.
文摘Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.
基金supported by the National Natural Science Foundation of China(No.82373887)。
文摘Arthritis,encompassing osteoarthritis(OA),rheumatoid arthritis(RA),and gouty arthritis(GA),is a prevalent inflammatory disease that significantly impacts quality of life.Natural products(NPs),derived from animals,plants,marine organisms,and microorganisms,have demonstrated beneficial effects in arthritis treatment both domestically and internationally.These natural compounds offer advantages in drug discovery due to their skeletal diversity,structural complexity,and multi-effect,multi-target,and low-toxicity properties compared to conventional small-molecule medicines.However,unclear mechanisms have hindered the development and clinical application of NPs.This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment,emphasizing key NPs with therapeutic effects on OA,RA,and GA.It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis.Furthermore,this review provides insights into the future prospects of NP research in this field,which is crucial for advancing NP-based arthritis treatments.
基金supported by GILO Foundation.This research is in part supported by Korea Drug Development Fund funded by Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(RS-2023-00282595,Republic of Korea).
文摘Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.
基金supported in part by the National Natural Science Foundation of China(Grant No.82350710800,82374470,82202757)Shenzhen Medical Research Fund B2302005,and NHMRC,APP1163933.
文摘Rheumatoid arthritis(RA)is a prevalent and debilitating inflammatory disease that significantly impairs functional capacity and quality of life.RA accelerates musculoskeletal aging,leading to complications such as muscle degeneration and sarcopenia.Recent research has identified myopenia as a condition of significant muscle loss associated with illness,distinct from the muscle wasting seen in other chronic diseases like cancer cachexia or heart failure.In RA,myopenia is characterized by muscle depletion without concurrent significant fat loss,and it can affect individuals of all ages.While inflammation plays a central role,it is not the sole factor contributing to the high incidence of muscle wasting in RA.In subsequent discussions,secondary sarcopenia will be considered alongside myopenia,as both involve muscle wasting decline primarily due to disease.This review summarizes recent findings on the impact of RA-related myopenia and secondary sarcopenia on functional capacity,explores its underlying mechanisms,and discusses contemporary strategies to mitigate the process of musculoskeletal aging in RA patients.
基金supported by the National Natural Science Foundation of China(NSFC)(No.82130073,No.82372430,No.31871431,No.31821002,No.32101011,No.22177073)Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System+3 种基金Shanghai Science and Technology Committee(No.23ZR1437600,No.24410710600,No.24141901302)Shenzhen Medical Research Fund(No.B2302005)The Open Project Funding of Shanghai Key Laboratory of Orthopedics(No.KFKT202201)Biomaterials and Regenerative Medicine Institute Cooperative,Research Project,Shanghai Jiao Tong University School of Medicine(No.2022LHA01).
文摘Itaconate,a macrophage-specific anti-inflammatory metabolite,has recently emerged as a critical regulator in rheumatoid arthritis pathogenesis.We found that itaconate is a TNF-αresponsive metabolite significantly elevated in the serum and synovial fluid of rheumatoid arthritis patients and we demonstrated that itaconate is primarily produced by inflammatory macrophages rather than osteoclasts or osteoblasts.In TNF-transgenic and Irg1−/−hybrid mice,a more severe bone destruction phenotype was observed.
基金the National Natural Science Foundation of China(82372412)the Social Development Project of Jiangsu Province(BE2022701)+4 种基金the Top Talent Support Program for Young and Middle-aged People of the Wuxi Health Committee(BJ2020044,BJ2020057,HB2020043)the Fundamental Research Funds of the Health and Family Planning Commission of Wuxi(M202024)the Special Program for Translational Medicine Research of the Wuxi Translational Medicine Center(2020DHYB07,2020DHYB03)the Key Special Project of Precision Medicine of the Wuxi Health Commission(J202101)peking union medical college hospital talent cultivation program(UHB50192).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflammatory mediators in this process is well-established,the contribution of non-inflammatory regulators in SFs to joint pathology remains poorly understood.In this study,we investigated the non-inflammatory role of SFs in RA using a co-culture model,and found that SFs from RA patients promote apoptosis of human chondrocytes.Mechanistic investigations reveal that SFs can secrete small extracellular vesicles(sEVs),which are taken up by chondrocytes and induce chondrocyte apoptosis in both normal chondrocytes and chondrocytes from patients with RA.sEV-derived miRNA 15-29148 are identified as key signaling molecules mediating the apoptosis effects of chondrocytes.Further studies reveal that SF-derived miRNA 15-29148 targeting CIAPIN1 results in increased chondrocyte apoptosis.We further demonstrate that SF-derived miRNA 15-29148 is transferred to chondrocytes,exacerbating cartilage damage in vivo.Moreover,chondrocyte-specific aptamer-modified polyamidoamine nanoparticles not only ameliorated RA but also prevented its onset.This study suggests that,in RA,the secretion of specific sEV-miRNAs from SFs plays a crucial role in promoting chondrocyte apoptosis,potentially through non-inflammatory regulation,and that sEV-miRNA inhibition in SFs may represent an early preventive treatment strategy for cartilage degradation in RA.
文摘Post-traumatic osteoarthritis(PTOA)is a complex and painful problem in the foot and ankle.Ninety percent of osteoarthritis cases in the foot and ankle can be classified as post-traumatic.PTOA can affect any of the 33 joints in the foot and the ankle.Distraction arthroplasty is a method for treatment of early arthritic joints without fusing or replacing them and its effectiveness has been well documented.The purpose of this case series is to present our successful experiences and positive results using distraction arthroplasty to treat PTOA in the ankle,subtalar,first metatarsophalangeal,and second tarsometatarsal joints,and to present distraction arthroplasty as a viable alternative to invasive joint sacrificing procedures such as arthrodesis or arthroplasty.Distraction Arthroplasty effectively and safely treats PTOA and improves the stability of joints in the Foot and Ankle.Additionally,the use of bone marrow aspirate concentrate as an adjuvant can improve the long-term functional and structural outcomes of the joint,and can prolong the need for further,more aggressive surgical interventions such as fusion or arthroplasty.
基金National Natural Science Foundation of China(81774383)Major Project of Philosophy and Social Science Research in Colleges and Universities of Jiangsu Province (2020SJA0335)Graduate Research and Innovation Projects of Jiangsu Province (SJCX23_0735)。
文摘Objective To reveal the therapeutic effects of moxibustion in collagen-induced arthritis(CIA)rat models using the combined analysis of plasma and synovial membrane lipidomic profil-ing and to enhance the understanding of how moxibustion affects lipid metabolism in rheumatoid arthritis(RA).Methods A total of 32 male Sprague-Dawley(SD)rats were randomly assigned to four groups:control,moxibustion control(MC),model,and moxibustion model(MM)groups,with 8 rats in each group.CIA was induced in SD rats by two immunizations.The paw volume was mea-sured before the induction of CIA.Following induction,after assessing paw volume and arthritis index(AI)scores,the MC and MM groups received treatment at bilateral Shenshu(BL23)and Zusanli(ST36)acupoints for 10 min per acupoint.The intervention included three treatment courses,each spanning 6 d and followed by a 1-d interval.Paw volume and AI scores were assessed after each treatment course.After the completion of the three treatment courses,serum,plasma,synovial tissue,and ankle joint samples were collected.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-αin serum.Hematoxylin and eosin(HE)staining was per-formed for histopathological examination of the ankle joint tissues.Meanwhile,ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS)was utilized to analyze the plasma and synovial tissue sam-ples.In addition,multivariate statistical analysis was performed to identify differential lipid metabolites,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was applied to explore metabolic pathways modulated by moxibustion therapy.Results No significant difference in hind paw volume and AI scores was observed among the groups(P>0.05).After CIA induction,model group showed increased hind paw volume and AI scores compared with control group(P<0.05),which were significantly reduced after mox-ibustion treatment in MM group compared with model group(P<0.05).The levels of IL-6 and TNF-αwere significantly higher in model and MM groups compared with control group(P<0.05),but were lower in MM group than those in model group(P<0.05).Histopathologi-cal analysis showed improved cartilage and reduced inflammation in MM group.A total of 33 differential lipid metabolites in the plasma and 24 in the synovial membranes of CIA rat mod-els were identified when compared with control group.Among these lipid metabolites,31 in the plasma and all 24 in the synovial membranes were regulated by moxibustion treatment.Pathological analysis revealed upregulation of diacylglycerol(DG)and fatty acid(FA)levels,alongside downregulation of lysophosphatidylcholine(LPC),phosphatidylcholine(PC),and phosphatidylethanolamine(PE).Under physiological conditions,the treatment specifically reduced LPC and PC levels.Pathway enrichment analysis revealed that moxibustion predom-inantly affectedα-linolenic acid,glycerophospholipid,and sphingolipid metabolism under pathological conditions.Under physiological conditions,the regulation was centered aroundα-linolenic acid and glycerophospholipid metabolism.Conclusion The RA rat models exhibited significant lipid metabolic disturbances.Moxibus-tion alleviated paw swelling,reduced AI scores,modulated inflammatory cytokine levels,and partially corrected the altered levels of multiple lipid metabolites.The potential metabolic pathways implicated in the regulation of lipid metabolism under both physiological and pathological conditions includeα-linolenic acid,glycerophospholipid,and sphingolipid metabolism.
文摘Rheumatoid arthritis(RA)is a common chronic autoimmune disease characterized by joint pain,swelling and dysfunction[1].According to epidemiologic statistics,the incidence of RA is 1%–2%,and in severe cases,it can develop into joint deformity and disability,which brings a heavy burden to the family and society[2].However,the pathogenesis of RA is complex and involves multiple cellular interactions,which increases the difficulty of curing RA.Current therapeutic options,such as disease-modifying antirheumatic drugs,non-steroidal anti-inflammatory drugs,and biologics,still face the challenge of relapse after drug discontinuation[3,4].Therefore,the pathogenesis of RA needs to be analyzed in depth to break through the existing therapeutic bottlenecks and promote the iterative innovation of individualized diagnosis and treatment.
文摘BACKGROUND Juvenile arthritis damage index(JADI)is a tool that measures the degree of aggressiveness of the juvenile idiopathic arthritis(JIA)course and assesses articular[JADI-articular damage(JADI-A)]and extraarticular[JADI-extraarticular damage(JADI-E)]damage.While aggressive JIA often requires early bio-logic disease-modified antirheumatic drugs(bDMARDs),the utility of JADI as a predictor of treatment response remains underexplored.AIM To evaluate the potential of JADI as a predictor of bDMARD treatment response in JIA patients.METHODS This prospective study included 112 highly active non-systemic JIA biologic-naïve patients with a mean age of 12.2±4.6 years and a median disease duration of 2.5(interquartile range:1-5)years.Their clinical and radiological assessment,juvenile arthritis disease activity score 71,JADI-A,and JADI-E,were evaluated twice:Before the biologic initiation(baseline)and 12 months after(end of study).At baseline,50%had any damage,with 43%with articular damage and 23%with extraarticular damage.RESULTS During the study,JADI-A/JADI-E improved(33.9%/9.8%),worsened(8.9%/5.4%),or remained unchanged(57.1%/84.8%).Patients with baseline damage had higher markers of JIA activity:Polyarticular course,earlier onset age,ANA-positivity,and more active joints.Patients without initial structural damage(JADI“-”)were more likely(odds ratio=3.8,95%confidence interval:1.6-9.0,P<0.004)to achieve a low degree of activity or remission(46.2%),while on biological therapy,their scores were comparable to JADI-positive(18.3%).Pre-biological joint damage according to the JADI-A index(P=0.003),wrist(P=0.035),elbow(P=0.027),cervical spine limitation of motion(P=0.051),and erosions confirmed by magnetic resonance imaging(P=0.002),were associated with poor response to biological treatment and follow-up JIA activity.CONCLUSION Baseline structural damage in JIA is associated with diminished bDMARDs efficacy,increased disability,and shorter remission duration.JADI enhances conventional clinical risk stratification by facilitating timely initiation of bDMARDs,adherence to treat-to-target strategy and tailored patient care.
文摘Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples from patients with different pathological processes were collected, and the correlations between the subsets of FLSs and STMs and pathological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell assays, CCK- 8 assays and cell coculture were used to assess cell proliferation, migration and secretion of inflammatory factors. A collagen- induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytometry, micro- CT and staining. Results : Unique subsets of FLSs and STMs, namely, FAPα ^(+)THY1 − FLSs, FAPα ^(+)THY1 ^(+)FLSs, and MerTK ^(pos) TREM2 ^(high) STMs, were identified in synovial tissues from RA patients. The number of MerTK ^(pos) TREM2 ^(high) STMs was negatively correlated with the degree of damage in RA, while the number of FAPα ^(+)THY1 − FLSs was positively correlated with damage. On the one hand, emodin promoted the aggregation of MerTKposTREM2high STMs. Moreover, MerTK pos TREM2 high STM- mediated secretion of exosomes was promoted, which can inhibit the secretion of pro- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs and promote the secretion of anti- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs, thereby inhibiting FAPα ^(+)THY1 − FLS proliferation and migration, improving the local immune microenvironment, and inhibiting RA damage. Conclusion : Emodin was shown to regulate the aggregation of STM subsets and exosome secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA patients, suggesting that it has important clinical value.
文摘Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.
基金supported by the Budgeted Fund of Shanghai University of Traditional Chinese Medicine(Natural Science)(No.2021LK037)the Open Project of Qinghai Province Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation(No.2021-ZY-03).
文摘Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine preparation used to treat RA.ZF may cause liver injury.In this study,we aimed to develop a prediction model for abnormal liver function caused by ZF.Methods This retrospective study collected data from multiple centers from January 2018 to April 2023.Abnormal liver function was set as the target variable according to the alanine transaminase(ALT)level.Features were screened through univariate analysis and sequential forward selection for modeling.Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data.Results This study included 1,913 eligible patients.The LightGBM model exhibited the best performance(accuracy=0.96)out of the 10 learning models.The predictive metrics of the LightGBM model were as follows:precision=0.99,recall rate=0.97,F1_score=0.98,area under the curve(AUC)=0.98,sensitivity=0.97 and specificity=0.85 for predicting ALT<40 U/L;precision=0.60,recall rate=0.83,F1_score=0.70,AUC=0.98,sensitivity=0.83 and specificity=0.97 for predicting 40≤ALT<80 U/L;and precision=0.83,recall rate=0.63,F1_score=0.71,AUC=0.97,sensitivity=0.63 and specificity=1.00 for predicting ALT≥80 U/L.ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels,the combination of TNF-αinhibitors,JAK inhibitors,methotrexate+nonsteroidal anti-inflammatory drugs,leflunomide,smoking,older age,and females in middle-age(45-65 years old).Conclusion This study developed a model for predicting ZF-induced abnormal liver function,which may help improve the safety of integrated administration of ZF and Western medicine.
基金the National Natural Science Foundation of China(Nos.22325703,22377071,U23A6009)Research Project Supported by Shanxi Scholarship Council of China(No.2022-002)+1 种基金the Shanxi Province Science Foundation(No.202203021221009)Shanxi Province Science and Technology activities for overseas people selected funding project(No.2024001)。
文摘Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint deformity and dysfunction in severe cases.The pathologic development of RA involves complex interactions of multiple biomarkers,and detecting a single biomarker may produce falsepositive results due to other confounding factors.Therefore,fluorescent probes that can detect multiple biomarkers simultaneously are crucial for precise RA diagnosis.Peroxynitrite(ONOO^(-)) and viscosity are inflammation-related factors in cells.In this study,we developed a dual responsive near-infrared fluorescent probe,YLS,for ONOO^(-) and viscosity.The probe features dual-channel turn-on fluorescence responses at 625 and 760 nm upon the presence of ONOO^(-) and viscosity,respectively.Supported by YLS,we found that during RA pathology,lymphocyte infiltration not only increases the concentration of proteins in the joint fluid resulting in elevated viscosity;at the same time,the overproduction of ONOO^(-) exacerbates oxidative stress and inflammatory responses.This multiparameter assay is expected to improve the diagnostic accuracy of the early stages of RA,thus providing a scientific basis for early intervention and personalized treatment.
文摘BACKGROUND This study investigates the impact of type 2 diabetes mellitus(T2DM)on the risk of interstitial lung disease(ILD)and its subtypes in patients with rheumatoid arthritis(RA).RA is often complicated by ILD.T2DM has systemic proinflam-matory effects,but its impact on RA-related ILD is unclear.This research aims to elucidate the interplay between these conditions to inform clinical management and patient care strategies.AIM To determine if RA patients with T2DM have a higher occurrence of ILD compar-ed to RA patients without T2DM.METHODS We conducted a retrospective cohort study using the 2019-2020 National Inpa-tient Sample.Adult RA patients with and without T2DM were identified via International Classification of Diseases,10th Revision(ICD-10)codes.Propensity score matching(1:1)balanced 15+confounders.Logistic regression assessed the association of T2DM with ILD(overall and by subtype)and secondary outcomes(acute respiratory distress syndrome,pneumothorax,pleural effusion,pulmonary hypertension).Missing data were excluded.ILD subtypes were included based on ICD-10 codes and case count.RESULTS Among 199380 RA inpatients,ILD was more common in those with T2DM(2.25%)vs without(1.11%).After matching(n=121046),ILD remained higher in RA+T2DM[odds ratio(OR)=2.02,95%CI:1.84-2.22,P<0.001],with an absolute risk increase of about 1.14%.T2DM was associated with higher odds of ILD subtypes including usual interstitial pneumonia(OR=3.20)and non-specific interstitial pneumonia(OR=3.50).Other subtypes showed elevated ORs;eosinophilic pneumonia showed an inverse association(OR=0.23).PAH and pneumo-thorax were also more common in RA+T2DM(OR=1.40 and 1.85,respectively).Acute respiratory distress syn-drome and pleural effusion rates did not differ by T2DM status.Rare subtype findings should be interpreted cautiously.CONCLUSION T2DM increases ILD risk in RA and is linked to higher rates of pulmonary hypertension and pneumothorax,suggesting a role in exacerbating RA-related lung complications.
基金supported by the project of Central Funds Guiding the Local Science and Technology Development(No.20212ZDD02010)。
文摘Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis.Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling,improved body weights,and attenuated pathological changes in joints of rats with adjuvant-induced arthritis.Additionally,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and IL-1β in the serum and ankle joints were reduced.Bioinformatics analysis,along with the spleen index and measurements of IL-17 and IL-10 levels,suggested a potential relationship between AS and Th17 cells under arthritic conditions.In vitro,AS was shown to block Th17 cell differentiation,as evidenced by the reduced percentages of CD4^(+)IL-17A^(+)T cells and decreased expression levels of RORγt,IL-17A,IL-17F,IL-21,and IL-22,without affecting the cell viability and apoptosis.This effect was attributed to the limited glycolysis,as indicated by metabolomics analysis,reduced glucose uptake,and p H measurements.Further investigation revealed that AS might bind to hexokinase2(HK2)to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase(GAPDH)or pyruvate kinase M2(PKM2),and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation.Furthermore,AS impaired the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signals in vivo and in vitro,which was abolished by the addition of lactate.In conclusion,AS significantly improved adjuvant-induced arthritis(AIA)in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
