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
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 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
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
Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The d...Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The diagnosis of early rheumatoid arthritis(ERA)is crucial for effective treatment and prognosis of patients.Urine,as a diagnostic medium,offers the advantages of non-invasive diagnosis.Urinary metabolites can serve as biomarkers for diagnosis,prognosis,and risk prediction,improving specificity and accuracy.Methods:We recruited 37 ERA patients with a history of less than 3 months and a score of 6,26 osteoarthritis(OA)patients,and 30 healthy controls(HC).Urine samples were collected for 16S rRNA sequencing,and untargeted liquid chromatography-mass spectrometry(LC-MS)was used to detect metabolites.Bioinformatics approaches were employed to identify pathogenic metabolites as specific risk factors for ERA precisely.Results:2-methylnaphthalene was identified as a biomarker for ERA in urine.Prevotella,a major part of the urinary microbiome in ERA patients,exhibited a positive correlation with 2-methylnaphthalene.Notably,there were significant variations in urine metabolites among patients with ERA,OA,and HC.2-Methylnaphthalene was found to be significantly enriched in ERA.Besides,inflammatory factors were elevated in ERA patients.The research further demonstrated a positive correlation between rheumatoid factor(RF),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and the metabolite 2-methylnaphthalene.Conclusion:The urine metabolite 2-methylnaphthalene can be a risk factor for early urinary tract infections and may contribute to accurately screening early-risk metabolites in ERA.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
Introduction: Among the chronic and feared complications of this disease, rheumatoid vasculitis stands out as one of the most severe, albeit rare. The most frequently affected sites by rheumatoid vasculitis are the sk...Introduction: Among the chronic and feared complications of this disease, rheumatoid vasculitis stands out as one of the most severe, albeit rare. The most frequently affected sites by rheumatoid vasculitis are the skin and the peripheral nervous system. We report a case of rheumatoid vasculitis complicating a 30-year history of untreated rheumatoid arthritis. Case Report: The patient is a 75-year-old male with a 30-year history of deforming and erosive seropositive rheumatoid arthritis. He presented with polyarthritis and digital necrosis. Physical examination revealed peripheral joint syndrome with characteristic deformities of rheumatoid arthritis. Additionally, there was well-demarcated dry gangrene affecting the first and second digits of the right hand. Laboratory findings indicated an inflammatory syndrome. Tests for antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) to investigate other causes of vasculitis were negative. The patient received a corticosteroid bolus. After two weeks, there was a marked reduction in pain and an improvement in the general condition. The dry gangrene remained stable. Conclusion: Rheumatoid vasculitis remains a serious and chronic complication of rheumatoid arthritis, associated with significant mortality. This case highlights the crucial importance of early diagnosis and effective management of rheumatoid arthritis.展开更多
Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation.Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of...Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation.Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of inflammatory responses.The most prevalent chronic inflammatory illness,rheumatoid arthritis(RA),is typified by persistent synovitis thatmakes it hard for the disease to go away on its own.Interestingly,a unique subset of eosinophils known as regulatory eosinophils has been found in RA patients’synovium,especially while the disease is in remission.Pro-resolving signatures of regulatory eosinophils in the synovium are distinct from those of their lung counterparts.The most recent research on eosinophils and their function in this disease pathogenesis is compiled in this review.Based on the role of regulatory eosinophils,a new pathological model of inflammation resolution in RA is proposed,and potential therapeutic strategies aimed at enhancing the action of regulatory eosinophils in RA are proposed.展开更多
Objective To perform an in silico bioinformatics analysis to identify differentially expressed microRNAs(miRNAs)implicated in rheumatoid arthritis(RA)pathogenesis and evaluate their potential as biomarkers for assessi...Objective To perform an in silico bioinformatics analysis to identify differentially expressed microRNAs(miRNAs)implicated in rheumatoid arthritis(RA)pathogenesis and evaluate their potential as biomarkers for assessing therapeutic efficacy and monitoring acupuncture treatment.Methods miRNA microarray data(CEL and TXT formats)were acquired from human and murine RA models,with the latter undergoing acupuncture treatment.Data were normalized using the robust multi-array average(RMA)method and analyzed for differential expression.Differential expression analysis identified miRNAs through a comparative analysis of RA human tissues,acupuncture-treated murine RA models,and a bibliographic search for miRNAs implicated in RA pathogenesis and acupuncture treatment.Bioinformatics analysis was performed to identify potential target genes for each miRNA and signaling pathways via search tools for the Retrieval of Interacting Genes/Proteins(STRING)and ShinyGO.Gene-drug interaction analysis was performed through Drug-Gene Interaction Database(DGIdb)screening.Interaction networks were constructed with the Cytoscape v3.10.3 software.Results The hsa-miR-125a-5p and hsa-miR-125b-5p were identified as potential biomarkers associated with RA pathogenesis,presenting 468 and 455 target genes,respectively.These genes were enriched in 20 signaling pathways,including Janus kinasa-signal transducer and activator of transcription(JAK-STAT),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase-protein kinase B(PI3K-Akt),and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway,which have been associated with RA pathogenesis and progression.Drug-gene interaction networks revealed that 22 genes were significantly associated with 58 RA treatment drugs,among which 13 genes interacted with members of the hsa-miR-125 family.Conclusion The hsa-miR-125a-5p and hsa-miR-125b-5p demonstrate critical regulatory role in RA pathogenesis by modulating signaling pathways,including JAK-STAT,MAPK,PI3K-Akt,and NF-κB.Our findings show that the hsa-miR-125a-5p and hsa-miR-125b-5p exhibit differential expression patterns in response to pharmacological intervention in various diseases,including RA management.This suggests their potential roles as biomarkers for monitoring acupuncture treatment.Although existing evidence indicates that acupuncture can modify miRNA expression profiles,rigorous validation through biological models remains essential to confirm these results.展开更多
Abnormal activation of macrophages and osteoclasts(OCs)contributes significantly to rheumatoid arthritis(RA)development by secretion of numerous inflammatory factors.Notably,these cells exhibit significant upregulatio...Abnormal activation of macrophages and osteoclasts(OCs)contributes significantly to rheumatoid arthritis(RA)development by secretion of numerous inflammatory factors.Notably,these cells exhibit significant upregulation of folate receptor proteins on their surfaces.Unfortunately,there is a current lack of safe and effective therapeutic drugs for RA.Xuetongsu(XTS),a triterpenoid compound extracted fromKadsura heteroclita Roxb Craib,has demonstrated the ability to significantly inhibit the proliferation of RA fibroblast-like synoviocytes(RAFLS).However,its clinical application is hampered by poor targeting and short half-life.To address these drawbacks,we previously developed a nano-drug system named HRPS nanoparticles(NPs),which effectively targets RAFLS and inhibits synovial hyperplasia.However,this system overlooked the essential role of OCs in RA-related bone destruction.Therefore,we designed a novel folate-modified biomimetic Prussian blue(PB)-XTS NP(FMPX NP)for the selective delivery of XTS into inflammatory macrophages and OCs.The NP exhibits an excellent photothermal effect when assisted by laser irradiation,facilitating targeted release of XTS within inflammatory macrophages and OCs.The synergistic anti-inflammatory and reactive oxygen species scavenging effects of PB NPs and XTS are mediated by the inhibition of the NF-κB signaling pathway in inflammatory macrophages and RANK/RANKL/NFATc1 signaling pathway in OCs.In vivo experiments showed that FMPX NPs extended the half-life of XTS by 2.32 times,decreased hind foot swelling from 12.10±0.49 mm to 8.24±0.09 mm in the model group,and prevented bone damage.In conclusion,this study introduces a novel dual-targeted nano-based therapy for RA joints and highlights its potential for biochemical photothermal triple therapy for RA.FMPX NPs inhibit arthritis-related inflammation and bone destruction through a dual-target strategy,providing new insights for targeted drug therapies in clinical RA treatment.展开更多
Invasive fibroblast-like synoviocytes(FLS),inflammatory macrophages and osteoclasts are the main three contributors to rheumatoid arthritis(RA)progression by promoting synovial inflammation and destructing cartilage a...Invasive fibroblast-like synoviocytes(FLS),inflammatory macrophages and osteoclasts are the main three contributors to rheumatoid arthritis(RA)progression by promoting synovial inflammation and destructing cartilage and bone.Targeting these three cell types for restoring the inflammatory homeostasis microenvironment may be a promising anti-RA strategy.Herein,we prepared a reactive oxygen species(ROS)-responsive micelles(DPTM)to co-load dexamethasone(DEX)and pristimerin(PRI)for RA therapy.This ROS-responsive system exhibits the following advantages:(1)It makes use of the“ELVIS”effect for passive delivery and targeting the ROS environment of RA-related cells to rapidly release the payload drugs DEX and PRI.(2)Compared with free drugs,DPTM showed stronger effect on the inhibition of RA-FLS proliferation and the promotion of RA-FLS apoptosis.Moreover,DPTM could significantly weaken the migration ability of RA-FLS as indicated by the results of wound healing assay and transwell assay.(3)DPTM exerted stronger cellular uptake and anti-inflammatory effect in M1 macrophages.(4)In the model studying receptor activator of nuclear factor kappa-B ligand(RANKL)-induced differentiation of bone marrow-derived macrophages(BMDMs)to osteoclasts,DPTM showed a stronger inhibitory activity on osteoclast formation as compared to free drugs.Taken together,these results highlighted the potential of DPTM for targeted RA therapy via inhibition of RA-FLS abnormal activation,macrophage polarization and osteoclastogenesis.展开更多
Systemic administration of the anti-rheumatic drug methotrexate(MTX)for a long period of time may lead to therapeutic tolerance,various adverse effects,and potential harm to the immune system.Therapeutic nano-delivery...Systemic administration of the anti-rheumatic drug methotrexate(MTX)for a long period of time may lead to therapeutic tolerance,various adverse effects,and potential harm to the immune system.Therapeutic nano-delivery carriers constructed based on biologically active phenols provide a promising approach to enhance the therapeutic effect of anti-rheumatic drugs.Caffeic acid,a natural compound with anti-inflammatory properties,holds significant potential in the treatment of diverse inflammatory conditions.In this paper,we first constructed a nano-delivery platform for MTX using caffeic acid-based polyphenol polymer Ph-CaA-OH(PCOH),and investigated the treatment of rheumatoid arthritis(RA)at low drug administration doses(2.5 mg/kg).PCOH nanoparticles(NPs)could inhibit lipopolysaccharidesstimulated macrophage inducible nitric oxide synthase(iNOS)expression and pro-inflammatory differentiation in vitro.In vivo imaging revealed the rapid accumulation and sustained presence of PCOH NPs at inflamed joints in collagen induced-arthritis(CIA)mice.Therapeutic evaluation of CIA mice demonstrated that MTX@PCOH NPs were superior to free MTX in reducing the progression of RA and decreasing the expression of multiple pro-inflammatory cytokines without significant toxic effects.By enhancing drug aggregation at inflammatory joints and capitalizing on the synergistic effects of active carriers,MTX@PCOH NPs effectively minimized the required drug dosage and mitigated toxic side effects in RA treatment.The application of PCOH NPs to RA treatment provides a new strategy for the development of safer and more effective anti-RA nanomedicines.展开更多
Kinesiophobia is recognized as one of the primary barriers for patients participating in physical rehabilitation.This fear can create psychological obstacles to engaging in rehabilitation exercises or daily activities...Kinesiophobia is recognized as one of the primary barriers for patients participating in physical rehabilitation.This fear can create psychological obstacles to engaging in rehabilitation exercises or daily activities,leading to a significant decline in health-related quality of life.Currently,kinesiophobia has primarily been studied in the context of chronic pain and cardiovascular diseases,while its awareness and intervention in the field of Rheumatoid Arthritis have not received sufficient attention.Assisting patients in overcoming kinesiophobia is particularly crucial for initiating physical activity in Rheumatoid Arthritis.This article aims to review the assessment tools,influencing factors,and intervention strategies for kinesiophobia in patients with Rheumatoid Arthritis,with the goal of providing clinical healthcare professionals with references and insights for developing and implementing interventions,thereby promoting active rehabilitation among patients.展开更多
BACKGROUND Elevated liver enzymes in rheumatoid arthritis(RA)are often attributed to multiple factors including disease activity and treatment-related adverse effects.Tumor necrosis factor inhibitors(TNFi)have shown m...BACKGROUND Elevated liver enzymes in rheumatoid arthritis(RA)are often attributed to multiple factors including disease activity and treatment-related adverse effects.Tumor necrosis factor inhibitors(TNFi)have shown mixed effects on liver function,with varying safety profiles among agents.AIM To evaluate the hepatic safety of TNFi therapy—etanercept and adalimumab—in RA patients with elevated liver enzymes.METHODS A retrospective chart review was conducted for RA patients with elevated liver enzymes receiving TNFi at a single center between January 1,2019,and September 30,2024.Out of the patients screened,9 met the inclusion criteria.Trends in liver enzymes,fibrosis-4(FIB-4)score,and changes in the Child-Pugh class were analyzed at 1-year and 3-year follow-up periods.RESULTS Among 9 patients(4 on adalimumab,5 on etanercept),the median age was 56 years[interquartile range(IQR):49.5–64.5 years],77.8%were female,and the median body mass index was 36.99 kg/m²(IQR:30.95–43.43 kg/m²).Median baseline FIB-4 was 1.25(IQR:1.02–1.65),with no cirrhosis observed at baseline.Aspartate aminotransferase,alanine aminotransferase,and alkaline phosphatase levels declined consistently,with significant reductions from baseline to 3 years(P=0.003).FIB-4 scores also significantly decreased(P=0.003),while albumin,bilirubin,and Child-Pugh class remained stable at the 3-year follow-up.At 3 years,66.7%achieved RA remission(P=0.03).CONCLUSION TNFi therapy(adalimumab or etanercept)was associated with significant improvement in liver enzymes and FIB-4 without hepatic decompensation,supporting its safety in our cohort of RA patients with liver involvement.Larger prospective studies are warranted to further validate these findings.展开更多
This study aimed to systematically evaluate the clinical efficacy of combining wax therapy with conventional drug therapy for rheumatoid arthritis(RA)and to provide evidence supporting its clinical application.A compr...This study aimed to systematically evaluate the clinical efficacy of combining wax therapy with conventional drug therapy for rheumatoid arthritis(RA)and to provide evidence supporting its clinical application.A comprehensive search was conducted across PubMed,Cochrane Library,China Biomedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their inception to May 2024.Randomized controlled trials(RCTs)investigating the combination of wax therapy and conventional drug therapy for RA were included in the analysis.Statistical analysis was performed using Review Manager 5.3 software.Nine studies,encompassing a total of 843 patients,were included.The results demonstrated that the combination therapy significantly improved clinical efficacy compared to conventional drug therapy alone[RR=1.22,95%CI(1.11,1.34)].Moreover,the combination therapy led to notable improvements in DAS 28 scores[MD=-0.90,95%CI(-1.23,-0.57),P<0.00001],VAS scores[MD=-0.90,95%CI(-1.13,-0.66),P<0.00001],reduction in joint tenderness[MD=-1.27,95%CI(-1.81,-0.72),P<0.00001],decreased duration of morning stiffness[MD=-25.47,95%CI(-34.33,-16.61),P<0.00001],and lowered C-reactive protein levels[MD=-6.29,95%CI(-12.02,-0.57),P<0.05].In conclusion,wax therapy combined with conventional anti-rheumatic drugs significantly enhanced the clinical outcomes for RA patients by alleviating symptoms,reducing joint pain and morning stiffness,and decreasing inflammatory markers more effectively than conventional drug therapy alone.展开更多
Rheumatoid arthritis(RA),an autoimmune disease characterized by chronic inflammation of synovial tissue,is divided into two subtypes-anti-citrullinated protein antibody(ACPA)-positive and ACPA-negative RA.While the pa...Rheumatoid arthritis(RA),an autoimmune disease characterized by chronic inflammation of synovial tissue,is divided into two subtypes-anti-citrullinated protein antibody(ACPA)-positive and ACPA-negative RA.While the pathogenic mechanisms of ACPA-positive RA are well-understood,the etiology of ACPA-negative RA remains largely unknown.The association between RA and periodontitis(PD)has been observed since the early 190os,with the two diseases sharing common genetic and environmental risk factors that lead to the progressive destruction of bone and connective tissue.However,the associations between PD and the two subtypes of RA differ.This comprehensive review aims to provide an updated understanding of the epidemiological association between RA and PD,explore potential pathogenic mechanisms linking the two diseases,and highlight the key distinctions between the subtypes of RA and their respective associations with PD.We also discuss the possibility of early intervention or the treatment of the two diseases.Ultimately,this review aims to provide valuable insights for future research in this field.展开更多
Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was employed to analyze the chemical composition of three Clematidis Radix et Rhizoma sourced from different origins.Common characteristic c...Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was employed to analyze the chemical composition of three Clematidis Radix et Rhizoma sourced from different origins.Common characteristic components were identified through comprehensive literature review and the integration of fragment ion data.A rheumatoid arthritis(AA)model was induced in Sprague-Dawley(SD)rats using Freund’s complete adjuvant,and simultaneous administration of extracts from the three original plants of Clematidis Radix et Rhizoma,along with different doses of magnoflorine,was conducted to evaluate differences in therapeutic efficacy.A common characteristic component was identified,magnoflorine,present in Clematis chinensis Osbeck.Clematis hexapetala Pall.,and Clematis manshurica Rupr.Extracts from all three original plants,as well as each dose group of the Rhizomas of Clematis chinensis Osbeck.Clematis hexapetala Pall.,Clematis manshurica Rupr.,and magnoflorine,demonstrated efficacy in alleviating rheumatoid arthritis symptoms by enhancing cellular infiltration,reducing vascular opacification,and lowering serum levels of inflammatory factors.Magnoflorine has the potential to be used as a quality marker for the three original plants of Clematidis Radix et Rhizoma.Additionally,both the three original plants and magnoflorine exhibit therapeutic potential for rheumatoid arthritis,which provides a solid theoretical and experimental basis for the establishment of more scientifically grounded quality standards of Clematidis Radix et Rhizoma and promotes the rational utilization of medicinal resources.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
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
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.
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.
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.
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financially supported by the Natural Science Foundation of China(No.82003766)Taishan Scholars Program(NO.tsqn202211219)+1 种基金the Key Research and Development Project of Shandong Province(No.2021ZDSYS27)Shandong Province nature fund surface project(Grant No.ZR2024MH088)。
文摘Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The diagnosis of early rheumatoid arthritis(ERA)is crucial for effective treatment and prognosis of patients.Urine,as a diagnostic medium,offers the advantages of non-invasive diagnosis.Urinary metabolites can serve as biomarkers for diagnosis,prognosis,and risk prediction,improving specificity and accuracy.Methods:We recruited 37 ERA patients with a history of less than 3 months and a score of 6,26 osteoarthritis(OA)patients,and 30 healthy controls(HC).Urine samples were collected for 16S rRNA sequencing,and untargeted liquid chromatography-mass spectrometry(LC-MS)was used to detect metabolites.Bioinformatics approaches were employed to identify pathogenic metabolites as specific risk factors for ERA precisely.Results:2-methylnaphthalene was identified as a biomarker for ERA in urine.Prevotella,a major part of the urinary microbiome in ERA patients,exhibited a positive correlation with 2-methylnaphthalene.Notably,there were significant variations in urine metabolites among patients with ERA,OA,and HC.2-Methylnaphthalene was found to be significantly enriched in ERA.Besides,inflammatory factors were elevated in ERA patients.The research further demonstrated a positive correlation between rheumatoid factor(RF),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and the metabolite 2-methylnaphthalene.Conclusion:The urine metabolite 2-methylnaphthalene can be a risk factor for early urinary tract infections and may contribute to accurately screening early-risk metabolites in ERA.
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.
文摘Introduction: Among the chronic and feared complications of this disease, rheumatoid vasculitis stands out as one of the most severe, albeit rare. The most frequently affected sites by rheumatoid vasculitis are the skin and the peripheral nervous system. We report a case of rheumatoid vasculitis complicating a 30-year history of untreated rheumatoid arthritis. Case Report: The patient is a 75-year-old male with a 30-year history of deforming and erosive seropositive rheumatoid arthritis. He presented with polyarthritis and digital necrosis. Physical examination revealed peripheral joint syndrome with characteristic deformities of rheumatoid arthritis. Additionally, there was well-demarcated dry gangrene affecting the first and second digits of the right hand. Laboratory findings indicated an inflammatory syndrome. Tests for antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) to investigate other causes of vasculitis were negative. The patient received a corticosteroid bolus. After two weeks, there was a marked reduction in pain and an improvement in the general condition. The dry gangrene remained stable. Conclusion: Rheumatoid vasculitis remains a serious and chronic complication of rheumatoid arthritis, associated with significant mortality. This case highlights the crucial importance of early diagnosis and effective management of rheumatoid arthritis.
基金supported by NIH grants to M Bukrinsky P30 AI117970by the“Creation of Experimental Laboratories in the Natural Sciences Program”and Basic Research Program at the Higher School of Economics University.
文摘Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation.Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of inflammatory responses.The most prevalent chronic inflammatory illness,rheumatoid arthritis(RA),is typified by persistent synovitis thatmakes it hard for the disease to go away on its own.Interestingly,a unique subset of eosinophils known as regulatory eosinophils has been found in RA patients’synovium,especially while the disease is in remission.Pro-resolving signatures of regulatory eosinophils in the synovium are distinct from those of their lung counterparts.The most recent research on eosinophils and their function in this disease pathogenesis is compiled in this review.Based on the role of regulatory eosinophils,a new pathological model of inflammation resolution in RA is proposed,and potential therapeutic strategies aimed at enhancing the action of regulatory eosinophils in RA are proposed.
基金Programa de Investigadores e Investigadoras of the Consejo Mexiquense de Ciencia y Tecnología(COMECYT)(EESP2024-0038)。
文摘Objective To perform an in silico bioinformatics analysis to identify differentially expressed microRNAs(miRNAs)implicated in rheumatoid arthritis(RA)pathogenesis and evaluate their potential as biomarkers for assessing therapeutic efficacy and monitoring acupuncture treatment.Methods miRNA microarray data(CEL and TXT formats)were acquired from human and murine RA models,with the latter undergoing acupuncture treatment.Data were normalized using the robust multi-array average(RMA)method and analyzed for differential expression.Differential expression analysis identified miRNAs through a comparative analysis of RA human tissues,acupuncture-treated murine RA models,and a bibliographic search for miRNAs implicated in RA pathogenesis and acupuncture treatment.Bioinformatics analysis was performed to identify potential target genes for each miRNA and signaling pathways via search tools for the Retrieval of Interacting Genes/Proteins(STRING)and ShinyGO.Gene-drug interaction analysis was performed through Drug-Gene Interaction Database(DGIdb)screening.Interaction networks were constructed with the Cytoscape v3.10.3 software.Results The hsa-miR-125a-5p and hsa-miR-125b-5p were identified as potential biomarkers associated with RA pathogenesis,presenting 468 and 455 target genes,respectively.These genes were enriched in 20 signaling pathways,including Janus kinasa-signal transducer and activator of transcription(JAK-STAT),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase-protein kinase B(PI3K-Akt),and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway,which have been associated with RA pathogenesis and progression.Drug-gene interaction networks revealed that 22 genes were significantly associated with 58 RA treatment drugs,among which 13 genes interacted with members of the hsa-miR-125 family.Conclusion The hsa-miR-125a-5p and hsa-miR-125b-5p demonstrate critical regulatory role in RA pathogenesis by modulating signaling pathways,including JAK-STAT,MAPK,PI3K-Akt,and NF-κB.Our findings show that the hsa-miR-125a-5p and hsa-miR-125b-5p exhibit differential expression patterns in response to pharmacological intervention in various diseases,including RA management.This suggests their potential roles as biomarkers for monitoring acupuncture treatment.Although existing evidence indicates that acupuncture can modify miRNA expression profiles,rigorous validation through biological models remains essential to confirm these results.
基金supported by National Natural Science Foundation of China(82204766,82074122,82174078)Natural Science Foundation of Hunan province(2023JJ40490)+9 种基金Changjiang Scholars Program in Ministry Education,People’s Republic of China(T2019133)Xiaohe Sci-Tech Talents Special Funding under Hunan Provincial Sci-Tech Talents Sponsorship Program(2023TJ-X71)Science and Technology Innovation Program of Hunan Province(2024RC3201)Scientific research project of Hunan Provincial Education Department(21B0394,21A0239)Research Project of Hunan Administration of Traditional Chinese Medicine(B2023055)Changsha Outstanding Innovative Youth Training Program(kq2306021)Outstanding Youth Program of Hunan University of Chinese Medicine(202202)Postgraduate Innovation Project of Hunan University of Chinese Medicine(2024CX090)Open Foundation Project of Hunan International Joint Laboratory of Traditional Chinese Medicine(2022GJSYS02)Undergraduate Research and Innovation Foundation of Hunan University of Chinese Medicine(2023BKS097).
文摘Abnormal activation of macrophages and osteoclasts(OCs)contributes significantly to rheumatoid arthritis(RA)development by secretion of numerous inflammatory factors.Notably,these cells exhibit significant upregulation of folate receptor proteins on their surfaces.Unfortunately,there is a current lack of safe and effective therapeutic drugs for RA.Xuetongsu(XTS),a triterpenoid compound extracted fromKadsura heteroclita Roxb Craib,has demonstrated the ability to significantly inhibit the proliferation of RA fibroblast-like synoviocytes(RAFLS).However,its clinical application is hampered by poor targeting and short half-life.To address these drawbacks,we previously developed a nano-drug system named HRPS nanoparticles(NPs),which effectively targets RAFLS and inhibits synovial hyperplasia.However,this system overlooked the essential role of OCs in RA-related bone destruction.Therefore,we designed a novel folate-modified biomimetic Prussian blue(PB)-XTS NP(FMPX NP)for the selective delivery of XTS into inflammatory macrophages and OCs.The NP exhibits an excellent photothermal effect when assisted by laser irradiation,facilitating targeted release of XTS within inflammatory macrophages and OCs.The synergistic anti-inflammatory and reactive oxygen species scavenging effects of PB NPs and XTS are mediated by the inhibition of the NF-κB signaling pathway in inflammatory macrophages and RANK/RANKL/NFATc1 signaling pathway in OCs.In vivo experiments showed that FMPX NPs extended the half-life of XTS by 2.32 times,decreased hind foot swelling from 12.10±0.49 mm to 8.24±0.09 mm in the model group,and prevented bone damage.In conclusion,this study introduces a novel dual-targeted nano-based therapy for RA joints and highlights its potential for biochemical photothermal triple therapy for RA.FMPX NPs inhibit arthritis-related inflammation and bone destruction through a dual-target strategy,providing new insights for targeted drug therapies in clinical RA treatment.
基金supported by the National Natural Science Foundation of China(No.82204724)the Science and Technology Development Fund,Macao SAR(Nos.0029/2023/AFJ,005/2023/SKL)+1 种基金the Multi-Year Research Grant(MYRG)of University of Macao(Nos.MYRG2022-00203-ICMS,MYRG-GRG2023-00134-ICMS-UMDF)Macao Young Scholars Program(No.AM2022019)。
文摘Invasive fibroblast-like synoviocytes(FLS),inflammatory macrophages and osteoclasts are the main three contributors to rheumatoid arthritis(RA)progression by promoting synovial inflammation and destructing cartilage and bone.Targeting these three cell types for restoring the inflammatory homeostasis microenvironment may be a promising anti-RA strategy.Herein,we prepared a reactive oxygen species(ROS)-responsive micelles(DPTM)to co-load dexamethasone(DEX)and pristimerin(PRI)for RA therapy.This ROS-responsive system exhibits the following advantages:(1)It makes use of the“ELVIS”effect for passive delivery and targeting the ROS environment of RA-related cells to rapidly release the payload drugs DEX and PRI.(2)Compared with free drugs,DPTM showed stronger effect on the inhibition of RA-FLS proliferation and the promotion of RA-FLS apoptosis.Moreover,DPTM could significantly weaken the migration ability of RA-FLS as indicated by the results of wound healing assay and transwell assay.(3)DPTM exerted stronger cellular uptake and anti-inflammatory effect in M1 macrophages.(4)In the model studying receptor activator of nuclear factor kappa-B ligand(RANKL)-induced differentiation of bone marrow-derived macrophages(BMDMs)to osteoclasts,DPTM showed a stronger inhibitory activity on osteoclast formation as compared to free drugs.Taken together,these results highlighted the potential of DPTM for targeted RA therapy via inhibition of RA-FLS abnormal activation,macrophage polarization and osteoclastogenesis.
基金supported by the National Natural Science Foundation of China(No.52173150)the Guangzhou Science and Technology Program City University Joint Funding Project(No.2023A03J0001)to Jun Wu+6 种基金supported by the National Natural Science Foundation of China(No.52073313)Shenzhen Science and Technology Program(No.KCXFZ 202002011010232)Longhua District Science and Innovation Commission Project Grants of Shenzhen(No.10162A20221027B1FA526)to Zhong Caosupported by Shenzhen Medical Research Fund(No.A2303010)National Natural Science Foundation of China(No.82204287)Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.87000-31670001)to Yi Zhaosupported by Guangdong Basic and Applied Basic Research Foundation(No.2023A1515220126)to Xinru You。
文摘Systemic administration of the anti-rheumatic drug methotrexate(MTX)for a long period of time may lead to therapeutic tolerance,various adverse effects,and potential harm to the immune system.Therapeutic nano-delivery carriers constructed based on biologically active phenols provide a promising approach to enhance the therapeutic effect of anti-rheumatic drugs.Caffeic acid,a natural compound with anti-inflammatory properties,holds significant potential in the treatment of diverse inflammatory conditions.In this paper,we first constructed a nano-delivery platform for MTX using caffeic acid-based polyphenol polymer Ph-CaA-OH(PCOH),and investigated the treatment of rheumatoid arthritis(RA)at low drug administration doses(2.5 mg/kg).PCOH nanoparticles(NPs)could inhibit lipopolysaccharidesstimulated macrophage inducible nitric oxide synthase(iNOS)expression and pro-inflammatory differentiation in vitro.In vivo imaging revealed the rapid accumulation and sustained presence of PCOH NPs at inflamed joints in collagen induced-arthritis(CIA)mice.Therapeutic evaluation of CIA mice demonstrated that MTX@PCOH NPs were superior to free MTX in reducing the progression of RA and decreasing the expression of multiple pro-inflammatory cytokines without significant toxic effects.By enhancing drug aggregation at inflammatory joints and capitalizing on the synergistic effects of active carriers,MTX@PCOH NPs effectively minimized the required drug dosage and mitigated toxic side effects in RA treatment.The application of PCOH NPs to RA treatment provides a new strategy for the development of safer and more effective anti-RA nanomedicines.
文摘Kinesiophobia is recognized as one of the primary barriers for patients participating in physical rehabilitation.This fear can create psychological obstacles to engaging in rehabilitation exercises or daily activities,leading to a significant decline in health-related quality of life.Currently,kinesiophobia has primarily been studied in the context of chronic pain and cardiovascular diseases,while its awareness and intervention in the field of Rheumatoid Arthritis have not received sufficient attention.Assisting patients in overcoming kinesiophobia is particularly crucial for initiating physical activity in Rheumatoid Arthritis.This article aims to review the assessment tools,influencing factors,and intervention strategies for kinesiophobia in patients with Rheumatoid Arthritis,with the goal of providing clinical healthcare professionals with references and insights for developing and implementing interventions,thereby promoting active rehabilitation among patients.
文摘BACKGROUND Elevated liver enzymes in rheumatoid arthritis(RA)are often attributed to multiple factors including disease activity and treatment-related adverse effects.Tumor necrosis factor inhibitors(TNFi)have shown mixed effects on liver function,with varying safety profiles among agents.AIM To evaluate the hepatic safety of TNFi therapy—etanercept and adalimumab—in RA patients with elevated liver enzymes.METHODS A retrospective chart review was conducted for RA patients with elevated liver enzymes receiving TNFi at a single center between January 1,2019,and September 30,2024.Out of the patients screened,9 met the inclusion criteria.Trends in liver enzymes,fibrosis-4(FIB-4)score,and changes in the Child-Pugh class were analyzed at 1-year and 3-year follow-up periods.RESULTS Among 9 patients(4 on adalimumab,5 on etanercept),the median age was 56 years[interquartile range(IQR):49.5–64.5 years],77.8%were female,and the median body mass index was 36.99 kg/m²(IQR:30.95–43.43 kg/m²).Median baseline FIB-4 was 1.25(IQR:1.02–1.65),with no cirrhosis observed at baseline.Aspartate aminotransferase,alanine aminotransferase,and alkaline phosphatase levels declined consistently,with significant reductions from baseline to 3 years(P=0.003).FIB-4 scores also significantly decreased(P=0.003),while albumin,bilirubin,and Child-Pugh class remained stable at the 3-year follow-up.At 3 years,66.7%achieved RA remission(P=0.03).CONCLUSION TNFi therapy(adalimumab or etanercept)was associated with significant improvement in liver enzymes and FIB-4 without hepatic decompensation,supporting its safety in our cohort of RA patients with liver involvement.Larger prospective studies are warranted to further validate these findings.
基金supported by the Key Research and Development Program of Yunnan Science and Technology Department(Grant No.202303AC100326)the National Natural Science Foundation of China(Grant No.81960863)the Education Department of Yunnan Province(Grant No.2023Y0463 and 2024Y380).
文摘This study aimed to systematically evaluate the clinical efficacy of combining wax therapy with conventional drug therapy for rheumatoid arthritis(RA)and to provide evidence supporting its clinical application.A comprehensive search was conducted across PubMed,Cochrane Library,China Biomedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their inception to May 2024.Randomized controlled trials(RCTs)investigating the combination of wax therapy and conventional drug therapy for RA were included in the analysis.Statistical analysis was performed using Review Manager 5.3 software.Nine studies,encompassing a total of 843 patients,were included.The results demonstrated that the combination therapy significantly improved clinical efficacy compared to conventional drug therapy alone[RR=1.22,95%CI(1.11,1.34)].Moreover,the combination therapy led to notable improvements in DAS 28 scores[MD=-0.90,95%CI(-1.23,-0.57),P<0.00001],VAS scores[MD=-0.90,95%CI(-1.13,-0.66),P<0.00001],reduction in joint tenderness[MD=-1.27,95%CI(-1.81,-0.72),P<0.00001],decreased duration of morning stiffness[MD=-25.47,95%CI(-34.33,-16.61),P<0.00001],and lowered C-reactive protein levels[MD=-6.29,95%CI(-12.02,-0.57),P<0.05].In conclusion,wax therapy combined with conventional anti-rheumatic drugs significantly enhanced the clinical outcomes for RA patients by alleviating symptoms,reducing joint pain and morning stiffness,and decreasing inflammatory markers more effectively than conventional drug therapy alone.
基金supported by the National Natural Science Foundation of China(Nos.82171768,81701600,and 82001048)the National Key Research and Development Program of China(No.2022YFC3602000)the Young Elite Scientist Support Program by CSA(Chinese Stomatological Association)(No.2020PYRC001).
文摘Rheumatoid arthritis(RA),an autoimmune disease characterized by chronic inflammation of synovial tissue,is divided into two subtypes-anti-citrullinated protein antibody(ACPA)-positive and ACPA-negative RA.While the pathogenic mechanisms of ACPA-positive RA are well-understood,the etiology of ACPA-negative RA remains largely unknown.The association between RA and periodontitis(PD)has been observed since the early 190os,with the two diseases sharing common genetic and environmental risk factors that lead to the progressive destruction of bone and connective tissue.However,the associations between PD and the two subtypes of RA differ.This comprehensive review aims to provide an updated understanding of the epidemiological association between RA and PD,explore potential pathogenic mechanisms linking the two diseases,and highlight the key distinctions between the subtypes of RA and their respective associations with PD.We also discuss the possibility of early intervention or the treatment of the two diseases.Ultimately,this review aims to provide valuable insights for future research in this field.
基金support from various sources including 2023 Basic Research Project of Colleges and Universities of Liaoning Provincial Department of Education(JYTZD2023137)Career Development Support Plan for Young and Middle-aged Teachers in Shenyang Pharmaceutical University(ZQN2021014)+2 种基金2024 Basic Scientific Research Funding Project of Liaoning Provincial Department of Education(LJ212410163051)Liaoning Province Science and Technology Plan Joint Plan(2024-MSLH-448)Liaoning Provincial Innovation Capacity Promotion Joint Fund(2022-NLTS-12-01).
文摘Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was employed to analyze the chemical composition of three Clematidis Radix et Rhizoma sourced from different origins.Common characteristic components were identified through comprehensive literature review and the integration of fragment ion data.A rheumatoid arthritis(AA)model was induced in Sprague-Dawley(SD)rats using Freund’s complete adjuvant,and simultaneous administration of extracts from the three original plants of Clematidis Radix et Rhizoma,along with different doses of magnoflorine,was conducted to evaluate differences in therapeutic efficacy.A common characteristic component was identified,magnoflorine,present in Clematis chinensis Osbeck.Clematis hexapetala Pall.,and Clematis manshurica Rupr.Extracts from all three original plants,as well as each dose group of the Rhizomas of Clematis chinensis Osbeck.Clematis hexapetala Pall.,Clematis manshurica Rupr.,and magnoflorine,demonstrated efficacy in alleviating rheumatoid arthritis symptoms by enhancing cellular infiltration,reducing vascular opacification,and lowering serum levels of inflammatory factors.Magnoflorine has the potential to be used as a quality marker for the three original plants of Clematidis Radix et Rhizoma.Additionally,both the three original plants and magnoflorine exhibit therapeutic potential for rheumatoid arthritis,which provides a solid theoretical and experimental basis for the establishment of more scientifically grounded quality standards of Clematidis Radix et Rhizoma and promotes the rational utilization of medicinal resources.
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.
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.
