Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affec...Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.展开更多
Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii H...Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.展开更多
Rheumatoid Arthritis(RA)is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life.Every year,millions of people are diagnosed with RA worldwide,particularl...Rheumatoid Arthritis(RA)is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life.Every year,millions of people are diagnosed with RA worldwide,particularly among elderly individuals and women.Therefore,there is a global need to develop new biomaterials,medicines and therapeutic methods for treating RA.This will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global scale.Hydrogels are soft and cross-linked polymeric materials that can store a chunk of fluids,drugs and biomolecules for hydration and therapeutic applications.Hydrogels are biocompatible and exhibit excellent mechanical properties,such as providing elastic cushions to articulating joints by mimicking the natural synovial fluid.Hence,hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and friction.Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage,thus exhibiting high potential for treating RA.This work reviews the progress in injectable and implantable hydrogels,synthesis methods,types of drugs,advantages and challenges.Additionally,it discusses the role of hydrogels in targeted drug delivery,mechanistic behaviour and tribological performance for RA treatment.展开更多
Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improv...Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)treatment.MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 phenotype.Furthermore,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis model.Moreover,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment effects.Overall,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.展开更多
In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of t...In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of the chemical ingredients of CZ-HB using TCMSP database. Subsequently, we predicted the targets corresponding to the active ingredients through the SwissTargetPrediction database. We constructed a comprehensive drug-ingredient-target network using Cytoscape (v 3.8.0), with the main ingredients of the drugs identified based on their degree values. We conducted a meticulous search across GEO, GeneCards, Therapeutic Target Database (TTD), and PharmGkb databases to identify target proteins associated with RA. The intersection of targets corresponding to the drugs' active ingredients and those associated with RA provided crucial insights. Functional analysis, including GO and KEGG pathway enrichment analyses, was performed on the intersecting targets using R (v 4.2.2). Additionally, a protein-protein interaction (PPI) network of the intersecting targets was constructed using the String platform. The resulting drug-ingredient-target-disease topology network was visualized using Cytoscape (v 3.8.0), and the Cytohubba plugin facilitated the identification of hub genes. The study revealed 35 active ingredients of CZ-HB and their corresponding 673 targets. We identified 14 major active ingredients crucial to the drug’s effects by focusing on the degree values. Furthermore, our investigation uncovered 784 targets associated with RA. Through the intersection of drug and disease targets, we pinpointed 34 active ingredients of CZ-HB capable of acting on 126 targets implicated in RA. The topological network analysis of the intersected genes identified five hub genes. The binding affinity of these hub genes to the 14 primary active ingredients of the drug was confirmed through molecular docking. The enrichment results of the intersecting genes suggested that CZ-HB exerted its anti-RA effects through a multi-component, multi-target, and multi-pathway approach.展开更多
Qianjinba is derived from the dried root of a legume vine and is known for its plant polysaccharide,which has demonstrated anti-inflammatory,analgesic,and neuroprotective properties.Despite these known effects,its imm...Qianjinba is derived from the dried root of a legume vine and is known for its plant polysaccharide,which has demonstrated anti-inflammatory,analgesic,and neuroprotective properties.Despite these known effects,its immunomodulatory potential remains underexplored.This study aimed to investigate the immunoregulatory effects of Qianjinba polysaccharide(QJBDT)in a murine model of rheumatoid arthritis(RA)and elucidate its mechanism of action in inhibiting the disease.To assess the immunomodulatory effects,RAW264.7 macrophage cells were stimulated with bacterial lipopolysaccharide(LPS)and subsequently treated with varying concentrations of QJBDT or total glucoside of paeonic acid(TGP).Cell proliferation and the expression levels of mitogen-activated protein kinase p38 and nuclear factor NF-κB proteins were evaluated.Following the successful modeling of RA in mice,different doses of QJBDT and TGP were administered via intragastric administration once daily for 21 d.Mice were divided into normal,model,QJBDT low-,medium-,and high-dose groups,along with a positive control group(TGP group),each comprising 10 mice.Organ coefficients were calculated,immune indexes in blood cells were determined,and alterations in T helper cell 17(Th17)and regulatory T cells(Treg)were analyzed using flow cytometry.Compared to the normal group,cell proliferation rates significantly increased across all groups(P<0.05).Elevated expressions of p38 and NF-κB proteins were observed in the model group,QJBDT low-and medium-dose groups(P<0.05).Various systemic immune inflammation indexes,including systemic immune inflammation index(SII),total inflammation systemic index(AISI),and systemic inflammation response index(SIRI),platelet-to-lymphocyte ratio(PLR),neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),showed increments(P<0.05).Additionally,body weight and organ coefficients of the thymus,spleen,and liver decreased in both the model and low-dose groups(P<0.05).Moreover,Th17 levels increased while Treg levels decreased across all groups(P<0.05),resulting in a heightened Th17 to Treg ratio in the model and low-dose groups(P<0.05).Notably,the QJBDT medium-dose,high-dose,and positive control groups demonstrated significant inhibitory effects on cell proliferation compared to the model group(P<0.05),along with reduced expression levels of p38 and NF-κB(P<0.05).Furthermore,various immune indicators from routine blood tests exhibited different degrees of decrease(P<0.05),while immune indices displayed increases(P<0.05).The low-,medium-,and high-dose groups of QJBDT,as well as the positive control group,showed decreased Th17 levels,elevated Treg levels,and diminished Th17 to Treg ratios(P<0.05).Additionally,there was no statistically significant difference in efficacy between the QJBDT high-dose and TGP groups(P>0.05).In conclusion,this study demonstrated that QJBDT exerted potent immunomodulatory effects on RA in mice in a dose-dependent manner.Its mechanism of action might involve the inhibition of NF-κB activation by suppressing the p38 MAPK signaling pathway.展开更多
Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders t...Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of RA.Neutrophil extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune response.NETs have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint damage.This article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.展开更多
BACKGROUND Gout and seronegative rheumatoid arthritis(SNRA)are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported.Limited information is available regarding the clinical m...BACKGROUND Gout and seronegative rheumatoid arthritis(SNRA)are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported.Limited information is available regarding the clinical management and prognosis of these combined diseases.CASE SUMMARY A 57-year-old woman with a 20-year history of joint swelling,tenderness,and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA.The initial regimen of methotrexate,leflunomide,and celecoxib alleviated her symptoms,except for those associated with the knee.After symptom recurrence after medication cessation,her regimen was updated to include iguratimod,methotrexate,methylprednisolone,and folic acid,but her knee issues persisted.Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee,indicating coexistent SNRA and atypical knee gout.After postarthroscopic surgery to remove the synovium and urate crystals,and following a tailored regimen of methotrexate,leflunomide,celecoxib,benzbromarone,and allopurinol,her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year,indicating successful management of both conditions.CONCLUSION This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.展开更多
[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the...[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by immunofluorescence.Western blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by ELISA.In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3CA was verified by double luciferin and Westen blot analysis.The expression of let-7i-3p and PI3K before and after baicalin intervention was detected by RT-qPCR.let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and IL-18.let-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of PIK3CA.Baicalin attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.展开更多
Objective:Rheumatoid arthritis(RA)requires comprehensive management.Structured nursing protocols may enhance outcomes,but evidence is limited.This study evaluated the effect of a structured nursing protocol on RA outc...Objective:Rheumatoid arthritis(RA)requires comprehensive management.Structured nursing protocols may enhance outcomes,but evidence is limited.This study evaluated the effect of a structured nursing protocol on RA outcomes.Materials and Methods:In this one-group pre-post study,30 Egyptian RA patients completed assessments before and after a 12-week nursing protocol comprising education,psychosocial support,and self-management promotion.Assessments included clinical evaluation of joint counts,erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and patient-reported Arthritis Self-Efficacy Scale(ASES),Health Assessment Questionnaire(HAQ),Visual Analog Scale(VAS)for pain,and Hospital Anxiety and Depression Scale(HADS).Results:The study demonstrated significant improvements in both clinical-and patient-reported outcomes.Joint count decreased from 18.4±4.2 to 14.2±3.8(P<0.001),ESR from 30.1±6.8 mm/h to 25.5±6.8 mm/h(P<0.01),and CRP levels from 15.2±3.6 mg/L to 11.8±2.9 mg/L(P<0.01)postintervention.Patient-reported outcomes showed a marked increase in ASES score from 140±25 to 170±30(P<0.001)and reductions in HAQ from 1.6±0.4 to 1.3±0.3(P<0.01),VAS pain score from 7.8±1.7 to 6.2±1.2(P<0.001),and HADS anxiety and depression scores from 11±3 to 8±2(P<0.05)and 10±2 to 7±1(P<0.05),respectively.Conclusion:A structured nursing protocol significantly improved clinical disease activity,physical functioning,pain,self-efficacy,and emotional well-being in RA patients.A multifaceted nursing intervention appears beneficial for optimizing RA outcomes.展开更多
Introduction: Rheumatoid arthritis (RA) is a chronic, erosive and deforming inflammatory rheumatic disease. In the era of biotherapies and the arrival of biosimilars in sub-Saharan Africa, the objective of this study ...Introduction: Rheumatoid arthritis (RA) is a chronic, erosive and deforming inflammatory rheumatic disease. In the era of biotherapies and the arrival of biosimilars in sub-Saharan Africa, the objective of this study was to describe plasma IL-6 variations in RA patients at Cité Verte District Hospital (Cameroon). Material and Methods: Descriptive and analytical cross-sectional study from December 1, 2021 to May 31, 2022. We included patients over 18 years old suffering from RA (ACR/EULAR 2010). Patients with an infection were not included. The data collected were age, sex, smoking status, family history, disease duration, disease activity by DAS28, CRP, rheumatoid factor, and plasma level of IL-6. Bone erosion was sought on radiography and ultrasound. Result: We included 31 patients, 25 of whom were women (80.6%). The mean age was 47.27 ± 17.97 years. Disease activity was predominantly moderate (32.3%) and severe (32.3%). Mean IL-6 level was 15.29 ± 2.36 pg/ml (extremes: 11.26 pg/ml and 20.15 pg/ml). IL-6 levels were higher in patients with a history of smoking. Similarly, IL-6 levels were higher in patients with mildly active RA in remission than in moderately and severely active RA. Mean IL-6 levels were significantly higher in patients with erosive RA (16.3 pg/ml VS 14.6 pg/ml). Conclusion: IL-6 levels were significantly elevated in men, weaned smokers and patients with bone erosions.展开更多
Objective:To explore the correlation between the change of D-dimer level and rheumatoid arthritis complicated with interstitial lung disease.Methods:From January 2022 to February 2024,20 rheumatoid arthritis patients ...Objective:To explore the correlation between the change of D-dimer level and rheumatoid arthritis complicated with interstitial lung disease.Methods:From January 2022 to February 2024,20 rheumatoid arthritis patients complicated with interstitial lung disease(interstitial lung disease group),20 rheumatoid arthritis patients without interstitial lung disease(without interstitial lung disease group),and 20 healthy people(control group)in Xijing Hospital were selected for this study.The fasting venous blood of the three groups of subjects was collected and their D-dimer,C-reactive protein(CRP),rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)were detected.Subsequently,the correlation between each index and rheumatoid arthritis complicated with interstitial lung disease was analyzed.Results:The D-dimer level of the interstitial lung disease group was significantly higher than the other two groups(P<0.05).The D-dimer level of the group without interstitial lung disease was significantly higher than the control group(P<0.05).CRP levels in the interstitial lung disease group and the group without interstitial lung disease were significantly higher than those of the control group(P<0.05).The ESR and RF levels of the interstitial lung disease group were significantly higher than the other two groups(P<0.05).The levels of ESR and RF levels of the group without interstitial lung disease were significantly higher than the control group(P<0.05).Conclusion:D-dimer levels of rheumatoid arthritis patients are higher than those of healthy individuals,and those complicated with interstitial lung disease present even higher levels.This finding shows that there is a correlation between D-dimer levels and rheumatoid arthritis with interstitial lung disease,which may facilitate the evaluation and diagnosis of this disease.展开更多
Objective:To study the effect of Helicobacter pylori infection on rheumatoid arthritis and T-lymphocyte subpopulations in patients with rheumatoid arthritis and to provide a new method for the treatment of rheumatoid ...Objective:To study the effect of Helicobacter pylori infection on rheumatoid arthritis and T-lymphocyte subpopulations in patients with rheumatoid arthritis and to provide a new method for the treatment of rheumatoid arthritis by removing Helicobacter pylori from patients.Methods:60 patients with rheumatoid arthritis admitted to the hospital from May 2022 to May 2023 were selected for the study,and all patients underwent a 13-carbon urea breath test to detect gastric H.pylori and the test results showed that 20 cases were negative and 40 cases were positive.The 40 positive patients were divided into the treatment group(n=20)and non-treatment group(n=20)by random number table method and the treatment group was given anti-Helicobacter pylori treatment,and the non-treatment group was given maintenance rheumatoid basic treatment,comparing the anti-cyclic citrulline peptide(CCP),DS28 score,peripheral blood T-lymphocyte subsets(CD4^(+)T-lymphocytes,CD8^(+)T-lymphocytes,CD4^(+)/CD8^(+)ratio)before and after the treatment of patients by 13-carbon urea respiration test(pylori-negative group,20 patients)and those who were positive for the treatment of H pylori(pylori-positive group,40 patients).Besides,the correlation of peripheral blood T-lymphocyte subsets and disease activity between treatment and non-treatment groups in the pylori-positive group was identified together with the correlation of DS28 scores,TNF-αlevels,sedimentation and immunoglobulin,lymphocyte subsets in the pylori-positive treatment group and positive non-treatment group as well as the level of globulin,lymphocyte subsets,and peripheral blood lymphocytes before and after treatment.Results:Before treatment,CCP,DS28 score,CD8^(+)T lymphocyte level of the pylori-negative group were lower than that of the positive group,and CD4^(+)T lymphocyte and CD4^(+)/CD8^(+)ratio were higher than that of the positive group(P<0.05);after treatment,the indexes of the pylori-positive group improved,and there was no significant difference in the comparison of the indexes with those of the pylori-negative group(P>0.05);the positive treatment group had a DS28(3.19±1.02)points,positive non-treatment group DS28(5.36±1.85)points,non-treatment group DS28 score and CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)negative correlation with CD8^(+)T lymphocytes showed a positive correlation(P<0.05);before the treatment,pylori-positive treatment group and non-treatment group DS28 scores,TNF-αlevels,peripheral blood T lymphocyte subpopulation levels were not significantly different(P>0.05);after treatment,DS28 score,TNF-αlevel,CD8^(+)T of the treatment group were lower than those of the non-treatment group,and CD4^(+)T lymphocytes and CD4^(+)/CD8^(+)ratio were higher than those of the non-treatment group(P<0.05).Conclusion:H.pylori affects the level of T lymphocyte subsets in patients with rheumatoid arthritis,and there is a certain correlation between the two.Removal of H.pylori can improve the level of T lymphocyte subsets,which is important for the treatment of patients with rheumatoid arthritis.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease characterized by synovitis.This disease tends to recur,persist,and is difficult to cure.The pathogenesis of RA is complex.Currently,the commonly used treatments...Rheumatoid arthritis(RA)is a systemic autoimmune disease characterized by synovitis.This disease tends to recur,persist,and is difficult to cure.The pathogenesis of RA is complex.Currently,the commonly used treatments for RA—non-steroidal anti-inflammatory drugs(NSAIDs),disease-modifying anti-rheumatic drugs(DMARDs),glucocorticoids,and immunosuppressants—have notable side effects with long-term use and may be ineffective for some patients.Therefore,it is crucial to find drugs with limited side effects and significant curative effects.Xinjiang's local characteristic drugs have a long history,abundant resources,and are known for their safety and effectiveness in treating RA.In recent years,many studies have reported on the mechanisms of action and therapeutic effects of Xinjiang's local characteristic drugs on RA.This article reviews the pathogenesis of RA,as well as the research progress and treatment characteristics of Xinjiang-featured drugs.展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints....Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.展开更多
BACKGROUND Various immune-mediated inflammatory diseases consisting of inflammatory bowel disease(IBD)and rheumatoid arthritis(RA),are found to have a substantial societal burden,increased healthcare costs,and progres...BACKGROUND Various immune-mediated inflammatory diseases consisting of inflammatory bowel disease(IBD)and rheumatoid arthritis(RA),are found to have a substantial societal burden,increased healthcare costs,and progressive disability.Studies suggest that patients with vs without comorbid depression have a more significant disability,a lower likelihood of remission,and reduced adherence to therapy.Elevated interleukin(IL)-1β,tumor necrosis factor-α,and IL-6 contribute to developing depression by the impaired physiological responses to stress,resulting in increased pain,fever,fatigue,and lack thereof of interest,and thus poor long-term outcomes.This study emphasizes the timely recognition of the prevalence of major depressive disorder(MDD)in patients with RA and IBD combined,thus preventing disability.AIM To identify the prevalence level and temporal trends of depression in hospitalized IBD-RA patients.METHODS All adult hospitalized patients from January 2000 to December 2019 in the nationwide inpatient sample(NIS)were captured.The study population included all patients with a primary or secondary IBD-RA overlap disease using corresponding international classification of diseases(ICD)-9 and ICD-10 codes.IBD includes Crohn’s disease and ulcerative colitis.The study population was divided into IBD-RA without MDD(controls)and IBD-RA with MDD(cases).For group comparison between MDD vs no MDD,we used Student’s t-test for continuous variables and RaoScott Chi-square tests for categorical variables.For univariate analyses,we used logistic regression,and for multivariate analysis,we used a weighted multi-level mixed-effects model.We attested all hypotheses with two-tailed significance level of 0.05(P<0.05 was considered significant).The outcome is to examine the temporal trends and prevalence of depression in patients with IBD-RA by gender,race,and age.RESULTS A total of 133315 records were identified with IBD-RA overlap,of which 26155 patients(19.62%)had MDD.Among the IBD-RA patients,those who had MDD were younger[mean age of 56 years(SD±15)]to IBD-RA without MDD patients with a P<0.0001,more females(80%among cases vs 73%among controls)than males with a P<0.0001,frequent in the white race(79%among cases vs 73%among controls)than black race.Over the 19 years,the number of patients with MDD in IBDRA increased from 153(the year 2000)to 2880(the year 2019)in weighted NIS,representing a 1782%increase compared to the year 2000 with a P<0.001.Factors associated with higher MDD included younger age,female gender,white race,alcohol,opioids,esophageal disorders,peptic ulcer disease,chronic pancreatitis,paralysis,dementia,menopausal disorders,obesity,nutritional deficiencies,diabetes mellitus with chronic complications,and osteoarthritis.CONCLUSION There is a rise in the prevalence of depression in younger patients with IBD-RA combined compared to their counterparts.These patients are also at higher risk for the increased cost of care and poor treatment compliance.It is crucial to educate the involved clinicians to identify the early signs and symptoms of depression in patients with IBD or RA or IBD-RA combined and treat them to have a better overall prognosis.展开更多
BACKGROUND Sporadic cases of rheumatoid arthritis(RA)due to unsatisfactory responses to Abatacept(ABT)have been reported;however,the rescue therapy has not been finalized.Here,we present a case with difficult-to-treat...BACKGROUND Sporadic cases of rheumatoid arthritis(RA)due to unsatisfactory responses to Abatacept(ABT)have been reported;however,the rescue therapy has not been finalized.Here,we present a case with difficult-to-treat RA(D2T RA)that was resistant to either a single ABT or a Janus kinase(JAK)inhibitor(Tofacitinib),but improved with a combination of ABT and JAK inhibitor(Baricitinib,BAT).CASE SUMMARY A 46-year-old Chinese woman who had RA for ten years that was resistant to Tocilizumab,Etanercept,Adalimumab,and ABT.According to the European League Against Rheumatism definition,the patient was diagnosed with D2T RA.It was then improved with a combination of ABT and a JAK inhibitor BAT.CONCLUSION ABT combined with BAT may be an acceptable strategy for treating D2T RA.展开更多
Scutellarin(SCU)is a herbal flavonoid glucuronide with multiple pharmacological activities,including antioxidant,anti-inflammation,vascular relaxation,anti-platelet,and myocardial protection.However,the effect of SCU...Scutellarin(SCU)is a herbal flavonoid glucuronide with multiple pharmacological activities,including antioxidant,anti-inflammation,vascular relaxation,anti-platelet,and myocardial protection.However,the effect of SCU on complete Freund’s adjuvant(CFA)-induced rheumatoid arthritis(RA)had not been studied.In this study,we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema.Enzyme-linked immunosorbent assay(ELISA)was carried out to evaluate the plasma levels of immunoglobulin(Ig)G,IgE,tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,receptor activator of nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG).Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints.The proportions of T helper type 1(Th1)and T helper type 2(Th2)cells of CD4+T lymphocyte subsets were analyzed by flow cytometry.The expression of Kelch-like ECHassociated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)was analyzed using real-time quantitative PCR(RT-qPCR)and western blotting assays.The present study demonstrated that SCU prevented CFA-induced RA,and inhibited the expression of inflammation factors,IgG,IgE,TNF-α,IL-1β,and IL-6.While SCU also reduced the RANKL level,it increased OPG expression in RA mice.The Th1/Th2 ratio was significantly lower in mice treated with SCU.Additionally,HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment.Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway.展开更多
Background:In this study,we investigated whether prophylactic treatment with Guizhi-Shaoyao-Zhimu decoction(GSZ)could delay the onset of rheumatoid arthritis by targeting mast cells.Methods:Collagen-induced arthritis ...Background:In this study,we investigated whether prophylactic treatment with Guizhi-Shaoyao-Zhimu decoction(GSZ)could delay the onset of rheumatoid arthritis by targeting mast cells.Methods:Collagen-induced arthritis was used to evaluate the effect of GSZ in preventing arthritis and joint destruction.Immunohistochemical staining revealed the accumulation of histamine H4 receptor and tryptase alpha/beta-1 in the ankle joint of the model.Then,we explored the effect of GSZ serum on fibroblast-like synoviocytes using standard transwell invasion and migration assays.Real-time quantitative polymerase chain reaction and western blot were used to detect the expression of toll-like receptor 4(TLR4)/myeloid differentiationfactor 88(MyD88)/nuclear factor-κB p65(NF-κB p65).Results:The results showed that pre-rheumatoid arthritis treatment with GSZ could reduce inflammation and maintain cartilage structure in the collagen-induced arthritis model.Moreover,GSZ significantly blocked mast cell degranulation and inhibited the TLR4/MyD88/NF-κB p65 pathway.Since the combined activation of mast cells via TLR4 and immune complexes enhances inflammation in synovial tissue,we concluded that GSZ may block mast cell degranulation by inhibiting the TLR4/MyD88/NF-κB p65 pathway and thus influence rheumatoid arthritis onset.Conclusion:Taken together,our data suggested that GSZ may be a promising therapeutic decoction for the prophylactic treatment of rheumatoid arthritis.展开更多
Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We establi...Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.展开更多
基金supported by the National Natural Science Foundation of China(82072432)the China-Japan Friendship Hospital Horizontal Project/Spontaneous Research Funding(2022-HX-JC-7)+1 种基金the National High Level Hospital Clinical Research Funding(2022-NHLHCRF-PY-20)the Elite Medical Professionals project of China-Japan Friendship Hospital(ZRJY2021-GG12).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A03807 and CI2021A01501)the National Natural Science Foundation of China(82330124)+2 种基金the Beijing Municipal Natural Science Foundation(7212186)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002)the Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences.
文摘Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.
基金supported by grant#SZ-SZSTI2010 by the Shenzhen Science and Technology Innovation Committee(SZSTI),Guang Dong Basic and Applied Basic Research Foundation(2022B1515130010)Hong Kong Research Grant Council(RGC)funding projects(GRF#16308818,GRF#16309920,and GRF#16309421)Hong Kong Innovation and Technology Commission(HKITC)funding project(MHP/003/19).
文摘Rheumatoid Arthritis(RA)is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life.Every year,millions of people are diagnosed with RA worldwide,particularly among elderly individuals and women.Therefore,there is a global need to develop new biomaterials,medicines and therapeutic methods for treating RA.This will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global scale.Hydrogels are soft and cross-linked polymeric materials that can store a chunk of fluids,drugs and biomolecules for hydration and therapeutic applications.Hydrogels are biocompatible and exhibit excellent mechanical properties,such as providing elastic cushions to articulating joints by mimicking the natural synovial fluid.Hence,hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and friction.Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage,thus exhibiting high potential for treating RA.This work reviews the progress in injectable and implantable hydrogels,synthesis methods,types of drugs,advantages and challenges.Additionally,it discusses the role of hydrogels in targeted drug delivery,mechanistic behaviour and tribological performance for RA treatment.
文摘Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)treatment.MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 phenotype.Furthermore,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis model.Moreover,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment effects.Overall,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.
基金National Natural Science Foundations of China (Grant No. 81960863)the Education Department of Yunnan Province (Grant No. 2023Y0463)。
文摘In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of the chemical ingredients of CZ-HB using TCMSP database. Subsequently, we predicted the targets corresponding to the active ingredients through the SwissTargetPrediction database. We constructed a comprehensive drug-ingredient-target network using Cytoscape (v 3.8.0), with the main ingredients of the drugs identified based on their degree values. We conducted a meticulous search across GEO, GeneCards, Therapeutic Target Database (TTD), and PharmGkb databases to identify target proteins associated with RA. The intersection of targets corresponding to the drugs' active ingredients and those associated with RA provided crucial insights. Functional analysis, including GO and KEGG pathway enrichment analyses, was performed on the intersecting targets using R (v 4.2.2). Additionally, a protein-protein interaction (PPI) network of the intersecting targets was constructed using the String platform. The resulting drug-ingredient-target-disease topology network was visualized using Cytoscape (v 3.8.0), and the Cytohubba plugin facilitated the identification of hub genes. The study revealed 35 active ingredients of CZ-HB and their corresponding 673 targets. We identified 14 major active ingredients crucial to the drug’s effects by focusing on the degree values. Furthermore, our investigation uncovered 784 targets associated with RA. Through the intersection of drug and disease targets, we pinpointed 34 active ingredients of CZ-HB capable of acting on 126 targets implicated in RA. The topological network analysis of the intersected genes identified five hub genes. The binding affinity of these hub genes to the 14 primary active ingredients of the drug was confirmed through molecular docking. The enrichment results of the intersecting genes suggested that CZ-HB exerted its anti-RA effects through a multi-component, multi-target, and multi-pathway approach.
基金Shandong Provincial Key Project of TCM Science and Technology(Grant No.2021Z051)Shandong Medical and Health Science and Technology Development Program(Grant No.202102040972)the Binzhou Medical College Student Innovation and Entrepreneurship Training Program(Grant No.X202210440354)。
文摘Qianjinba is derived from the dried root of a legume vine and is known for its plant polysaccharide,which has demonstrated anti-inflammatory,analgesic,and neuroprotective properties.Despite these known effects,its immunomodulatory potential remains underexplored.This study aimed to investigate the immunoregulatory effects of Qianjinba polysaccharide(QJBDT)in a murine model of rheumatoid arthritis(RA)and elucidate its mechanism of action in inhibiting the disease.To assess the immunomodulatory effects,RAW264.7 macrophage cells were stimulated with bacterial lipopolysaccharide(LPS)and subsequently treated with varying concentrations of QJBDT or total glucoside of paeonic acid(TGP).Cell proliferation and the expression levels of mitogen-activated protein kinase p38 and nuclear factor NF-κB proteins were evaluated.Following the successful modeling of RA in mice,different doses of QJBDT and TGP were administered via intragastric administration once daily for 21 d.Mice were divided into normal,model,QJBDT low-,medium-,and high-dose groups,along with a positive control group(TGP group),each comprising 10 mice.Organ coefficients were calculated,immune indexes in blood cells were determined,and alterations in T helper cell 17(Th17)and regulatory T cells(Treg)were analyzed using flow cytometry.Compared to the normal group,cell proliferation rates significantly increased across all groups(P<0.05).Elevated expressions of p38 and NF-κB proteins were observed in the model group,QJBDT low-and medium-dose groups(P<0.05).Various systemic immune inflammation indexes,including systemic immune inflammation index(SII),total inflammation systemic index(AISI),and systemic inflammation response index(SIRI),platelet-to-lymphocyte ratio(PLR),neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),showed increments(P<0.05).Additionally,body weight and organ coefficients of the thymus,spleen,and liver decreased in both the model and low-dose groups(P<0.05).Moreover,Th17 levels increased while Treg levels decreased across all groups(P<0.05),resulting in a heightened Th17 to Treg ratio in the model and low-dose groups(P<0.05).Notably,the QJBDT medium-dose,high-dose,and positive control groups demonstrated significant inhibitory effects on cell proliferation compared to the model group(P<0.05),along with reduced expression levels of p38 and NF-κB(P<0.05).Furthermore,various immune indicators from routine blood tests exhibited different degrees of decrease(P<0.05),while immune indices displayed increases(P<0.05).The low-,medium-,and high-dose groups of QJBDT,as well as the positive control group,showed decreased Th17 levels,elevated Treg levels,and diminished Th17 to Treg ratios(P<0.05).Additionally,there was no statistically significant difference in efficacy between the QJBDT high-dose and TGP groups(P>0.05).In conclusion,this study demonstrated that QJBDT exerted potent immunomodulatory effects on RA in mice in a dose-dependent manner.Its mechanism of action might involve the inhibition of NF-κB activation by suppressing the p38 MAPK signaling pathway.
基金supported by grants from the National Traditional Chinese Medicine Inheritance and Innovation Project Fund(Development and Reform Office[2022]366)National Key Discipline of Traditional Chinese Medicine(Traditional Chinese Medicine[2023]No.85)+2 种基金the Ministry of Science and Technology National Key Research and Development Program Chinese Medicine Modernization Research Key Project(2018YFC1705204)National Nature Fund Program(82074373,82274490,82205090)Anhui Provincial Laboratory of Applied Basis and Development of Internal Medicine of Modern Traditional Chinese Medicine(2016080503B041).
文摘Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of RA.Neutrophil extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune response.NETs have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint damage.This article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.
基金Supported by Natural Science Foundation of Guangdong Province,No.2023A1515011213。
文摘BACKGROUND Gout and seronegative rheumatoid arthritis(SNRA)are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported.Limited information is available regarding the clinical management and prognosis of these combined diseases.CASE SUMMARY A 57-year-old woman with a 20-year history of joint swelling,tenderness,and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA.The initial regimen of methotrexate,leflunomide,and celecoxib alleviated her symptoms,except for those associated with the knee.After symptom recurrence after medication cessation,her regimen was updated to include iguratimod,methotrexate,methylprednisolone,and folic acid,but her knee issues persisted.Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee,indicating coexistent SNRA and atypical knee gout.After postarthroscopic surgery to remove the synovium and urate crystals,and following a tailored regimen of methotrexate,leflunomide,celecoxib,benzbromarone,and allopurinol,her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year,indicating successful management of both conditions.CONCLUSION This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.
基金Supported by the National Natural Science Foundation of China(82360802):the Natural Science Foundation of Ningxia Province,China(2022AAC 03152).
文摘[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by immunofluorescence.Western blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by ELISA.In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3CA was verified by double luciferin and Westen blot analysis.The expression of let-7i-3p and PI3K before and after baicalin intervention was detected by RT-qPCR.let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and IL-18.let-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of PIK3CA.Baicalin attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.
文摘Objective:Rheumatoid arthritis(RA)requires comprehensive management.Structured nursing protocols may enhance outcomes,but evidence is limited.This study evaluated the effect of a structured nursing protocol on RA outcomes.Materials and Methods:In this one-group pre-post study,30 Egyptian RA patients completed assessments before and after a 12-week nursing protocol comprising education,psychosocial support,and self-management promotion.Assessments included clinical evaluation of joint counts,erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and patient-reported Arthritis Self-Efficacy Scale(ASES),Health Assessment Questionnaire(HAQ),Visual Analog Scale(VAS)for pain,and Hospital Anxiety and Depression Scale(HADS).Results:The study demonstrated significant improvements in both clinical-and patient-reported outcomes.Joint count decreased from 18.4±4.2 to 14.2±3.8(P<0.001),ESR from 30.1±6.8 mm/h to 25.5±6.8 mm/h(P<0.01),and CRP levels from 15.2±3.6 mg/L to 11.8±2.9 mg/L(P<0.01)postintervention.Patient-reported outcomes showed a marked increase in ASES score from 140±25 to 170±30(P<0.001)and reductions in HAQ from 1.6±0.4 to 1.3±0.3(P<0.01),VAS pain score from 7.8±1.7 to 6.2±1.2(P<0.001),and HADS anxiety and depression scores from 11±3 to 8±2(P<0.05)and 10±2 to 7±1(P<0.05),respectively.Conclusion:A structured nursing protocol significantly improved clinical disease activity,physical functioning,pain,self-efficacy,and emotional well-being in RA patients.A multifaceted nursing intervention appears beneficial for optimizing RA outcomes.
文摘Introduction: Rheumatoid arthritis (RA) is a chronic, erosive and deforming inflammatory rheumatic disease. In the era of biotherapies and the arrival of biosimilars in sub-Saharan Africa, the objective of this study was to describe plasma IL-6 variations in RA patients at Cité Verte District Hospital (Cameroon). Material and Methods: Descriptive and analytical cross-sectional study from December 1, 2021 to May 31, 2022. We included patients over 18 years old suffering from RA (ACR/EULAR 2010). Patients with an infection were not included. The data collected were age, sex, smoking status, family history, disease duration, disease activity by DAS28, CRP, rheumatoid factor, and plasma level of IL-6. Bone erosion was sought on radiography and ultrasound. Result: We included 31 patients, 25 of whom were women (80.6%). The mean age was 47.27 ± 17.97 years. Disease activity was predominantly moderate (32.3%) and severe (32.3%). Mean IL-6 level was 15.29 ± 2.36 pg/ml (extremes: 11.26 pg/ml and 20.15 pg/ml). IL-6 levels were higher in patients with a history of smoking. Similarly, IL-6 levels were higher in patients with mildly active RA in remission than in moderately and severely active RA. Mean IL-6 levels were significantly higher in patients with erosive RA (16.3 pg/ml VS 14.6 pg/ml). Conclusion: IL-6 levels were significantly elevated in men, weaned smokers and patients with bone erosions.
文摘Objective:To explore the correlation between the change of D-dimer level and rheumatoid arthritis complicated with interstitial lung disease.Methods:From January 2022 to February 2024,20 rheumatoid arthritis patients complicated with interstitial lung disease(interstitial lung disease group),20 rheumatoid arthritis patients without interstitial lung disease(without interstitial lung disease group),and 20 healthy people(control group)in Xijing Hospital were selected for this study.The fasting venous blood of the three groups of subjects was collected and their D-dimer,C-reactive protein(CRP),rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)were detected.Subsequently,the correlation between each index and rheumatoid arthritis complicated with interstitial lung disease was analyzed.Results:The D-dimer level of the interstitial lung disease group was significantly higher than the other two groups(P<0.05).The D-dimer level of the group without interstitial lung disease was significantly higher than the control group(P<0.05).CRP levels in the interstitial lung disease group and the group without interstitial lung disease were significantly higher than those of the control group(P<0.05).The ESR and RF levels of the interstitial lung disease group were significantly higher than the other two groups(P<0.05).The levels of ESR and RF levels of the group without interstitial lung disease were significantly higher than the control group(P<0.05).Conclusion:D-dimer levels of rheumatoid arthritis patients are higher than those of healthy individuals,and those complicated with interstitial lung disease present even higher levels.This finding shows that there is a correlation between D-dimer levels and rheumatoid arthritis with interstitial lung disease,which may facilitate the evaluation and diagnosis of this disease.
文摘Objective:To study the effect of Helicobacter pylori infection on rheumatoid arthritis and T-lymphocyte subpopulations in patients with rheumatoid arthritis and to provide a new method for the treatment of rheumatoid arthritis by removing Helicobacter pylori from patients.Methods:60 patients with rheumatoid arthritis admitted to the hospital from May 2022 to May 2023 were selected for the study,and all patients underwent a 13-carbon urea breath test to detect gastric H.pylori and the test results showed that 20 cases were negative and 40 cases were positive.The 40 positive patients were divided into the treatment group(n=20)and non-treatment group(n=20)by random number table method and the treatment group was given anti-Helicobacter pylori treatment,and the non-treatment group was given maintenance rheumatoid basic treatment,comparing the anti-cyclic citrulline peptide(CCP),DS28 score,peripheral blood T-lymphocyte subsets(CD4^(+)T-lymphocytes,CD8^(+)T-lymphocytes,CD4^(+)/CD8^(+)ratio)before and after the treatment of patients by 13-carbon urea respiration test(pylori-negative group,20 patients)and those who were positive for the treatment of H pylori(pylori-positive group,40 patients).Besides,the correlation of peripheral blood T-lymphocyte subsets and disease activity between treatment and non-treatment groups in the pylori-positive group was identified together with the correlation of DS28 scores,TNF-αlevels,sedimentation and immunoglobulin,lymphocyte subsets in the pylori-positive treatment group and positive non-treatment group as well as the level of globulin,lymphocyte subsets,and peripheral blood lymphocytes before and after treatment.Results:Before treatment,CCP,DS28 score,CD8^(+)T lymphocyte level of the pylori-negative group were lower than that of the positive group,and CD4^(+)T lymphocyte and CD4^(+)/CD8^(+)ratio were higher than that of the positive group(P<0.05);after treatment,the indexes of the pylori-positive group improved,and there was no significant difference in the comparison of the indexes with those of the pylori-negative group(P>0.05);the positive treatment group had a DS28(3.19±1.02)points,positive non-treatment group DS28(5.36±1.85)points,non-treatment group DS28 score and CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)negative correlation with CD8^(+)T lymphocytes showed a positive correlation(P<0.05);before the treatment,pylori-positive treatment group and non-treatment group DS28 scores,TNF-αlevels,peripheral blood T lymphocyte subpopulation levels were not significantly different(P>0.05);after treatment,DS28 score,TNF-αlevel,CD8^(+)T of the treatment group were lower than those of the non-treatment group,and CD4^(+)T lymphocytes and CD4^(+)/CD8^(+)ratio were higher than those of the non-treatment group(P<0.05).Conclusion:H.pylori affects the level of T lymphocyte subsets in patients with rheumatoid arthritis,and there is a certain correlation between the two.Removal of H.pylori can improve the level of T lymphocyte subsets,which is important for the treatment of patients with rheumatoid arthritis.
基金National Natural Science Foundation of China(No.82160841)Xinjiang Uygur Autonomous Region Natural Science Foundation Key Projects(2022D01D65).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease characterized by synovitis.This disease tends to recur,persist,and is difficult to cure.The pathogenesis of RA is complex.Currently,the commonly used treatments for RA—non-steroidal anti-inflammatory drugs(NSAIDs),disease-modifying anti-rheumatic drugs(DMARDs),glucocorticoids,and immunosuppressants—have notable side effects with long-term use and may be ineffective for some patients.Therefore,it is crucial to find drugs with limited side effects and significant curative effects.Xinjiang's local characteristic drugs have a long history,abundant resources,and are known for their safety and effectiveness in treating RA.In recent years,many studies have reported on the mechanisms of action and therapeutic effects of Xinjiang's local characteristic drugs on RA.This article reviews the pathogenesis of RA,as well as the research progress and treatment characteristics of Xinjiang-featured drugs.
基金financially supported by the National Natural Science Foundation of China (Nos. 82173758, China)Sichuan major science and technology project on biotechnology and medicine (2018SZDZX0018, China)
文摘Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.
文摘BACKGROUND Various immune-mediated inflammatory diseases consisting of inflammatory bowel disease(IBD)and rheumatoid arthritis(RA),are found to have a substantial societal burden,increased healthcare costs,and progressive disability.Studies suggest that patients with vs without comorbid depression have a more significant disability,a lower likelihood of remission,and reduced adherence to therapy.Elevated interleukin(IL)-1β,tumor necrosis factor-α,and IL-6 contribute to developing depression by the impaired physiological responses to stress,resulting in increased pain,fever,fatigue,and lack thereof of interest,and thus poor long-term outcomes.This study emphasizes the timely recognition of the prevalence of major depressive disorder(MDD)in patients with RA and IBD combined,thus preventing disability.AIM To identify the prevalence level and temporal trends of depression in hospitalized IBD-RA patients.METHODS All adult hospitalized patients from January 2000 to December 2019 in the nationwide inpatient sample(NIS)were captured.The study population included all patients with a primary or secondary IBD-RA overlap disease using corresponding international classification of diseases(ICD)-9 and ICD-10 codes.IBD includes Crohn’s disease and ulcerative colitis.The study population was divided into IBD-RA without MDD(controls)and IBD-RA with MDD(cases).For group comparison between MDD vs no MDD,we used Student’s t-test for continuous variables and RaoScott Chi-square tests for categorical variables.For univariate analyses,we used logistic regression,and for multivariate analysis,we used a weighted multi-level mixed-effects model.We attested all hypotheses with two-tailed significance level of 0.05(P<0.05 was considered significant).The outcome is to examine the temporal trends and prevalence of depression in patients with IBD-RA by gender,race,and age.RESULTS A total of 133315 records were identified with IBD-RA overlap,of which 26155 patients(19.62%)had MDD.Among the IBD-RA patients,those who had MDD were younger[mean age of 56 years(SD±15)]to IBD-RA without MDD patients with a P<0.0001,more females(80%among cases vs 73%among controls)than males with a P<0.0001,frequent in the white race(79%among cases vs 73%among controls)than black race.Over the 19 years,the number of patients with MDD in IBDRA increased from 153(the year 2000)to 2880(the year 2019)in weighted NIS,representing a 1782%increase compared to the year 2000 with a P<0.001.Factors associated with higher MDD included younger age,female gender,white race,alcohol,opioids,esophageal disorders,peptic ulcer disease,chronic pancreatitis,paralysis,dementia,menopausal disorders,obesity,nutritional deficiencies,diabetes mellitus with chronic complications,and osteoarthritis.CONCLUSION There is a rise in the prevalence of depression in younger patients with IBD-RA combined compared to their counterparts.These patients are also at higher risk for the increased cost of care and poor treatment compliance.It is crucial to educate the involved clinicians to identify the early signs and symptoms of depression in patients with IBD or RA or IBD-RA combined and treat them to have a better overall prognosis.
文摘BACKGROUND Sporadic cases of rheumatoid arthritis(RA)due to unsatisfactory responses to Abatacept(ABT)have been reported;however,the rescue therapy has not been finalized.Here,we present a case with difficult-to-treat RA(D2T RA)that was resistant to either a single ABT or a Janus kinase(JAK)inhibitor(Tofacitinib),but improved with a combination of ABT and JAK inhibitor(Baricitinib,BAT).CASE SUMMARY A 46-year-old Chinese woman who had RA for ten years that was resistant to Tocilizumab,Etanercept,Adalimumab,and ABT.According to the European League Against Rheumatism definition,the patient was diagnosed with D2T RA.It was then improved with a combination of ABT and a JAK inhibitor BAT.CONCLUSION ABT combined with BAT may be an acceptable strategy for treating D2T RA.
文摘Scutellarin(SCU)is a herbal flavonoid glucuronide with multiple pharmacological activities,including antioxidant,anti-inflammation,vascular relaxation,anti-platelet,and myocardial protection.However,the effect of SCU on complete Freund’s adjuvant(CFA)-induced rheumatoid arthritis(RA)had not been studied.In this study,we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema.Enzyme-linked immunosorbent assay(ELISA)was carried out to evaluate the plasma levels of immunoglobulin(Ig)G,IgE,tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,receptor activator of nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG).Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints.The proportions of T helper type 1(Th1)and T helper type 2(Th2)cells of CD4+T lymphocyte subsets were analyzed by flow cytometry.The expression of Kelch-like ECHassociated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)was analyzed using real-time quantitative PCR(RT-qPCR)and western blotting assays.The present study demonstrated that SCU prevented CFA-induced RA,and inhibited the expression of inflammation factors,IgG,IgE,TNF-α,IL-1β,and IL-6.While SCU also reduced the RANKL level,it increased OPG expression in RA mice.The Th1/Th2 ratio was significantly lower in mice treated with SCU.Additionally,HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment.Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway.
基金funded by Zhejiang Nature Science Foundation(LQ20H270006)National Key R&D Program of China(No.2018YFC1705500).
文摘Background:In this study,we investigated whether prophylactic treatment with Guizhi-Shaoyao-Zhimu decoction(GSZ)could delay the onset of rheumatoid arthritis by targeting mast cells.Methods:Collagen-induced arthritis was used to evaluate the effect of GSZ in preventing arthritis and joint destruction.Immunohistochemical staining revealed the accumulation of histamine H4 receptor and tryptase alpha/beta-1 in the ankle joint of the model.Then,we explored the effect of GSZ serum on fibroblast-like synoviocytes using standard transwell invasion and migration assays.Real-time quantitative polymerase chain reaction and western blot were used to detect the expression of toll-like receptor 4(TLR4)/myeloid differentiationfactor 88(MyD88)/nuclear factor-κB p65(NF-κB p65).Results:The results showed that pre-rheumatoid arthritis treatment with GSZ could reduce inflammation and maintain cartilage structure in the collagen-induced arthritis model.Moreover,GSZ significantly blocked mast cell degranulation and inhibited the TLR4/MyD88/NF-κB p65 pathway.Since the combined activation of mast cells via TLR4 and immune complexes enhances inflammation in synovial tissue,we concluded that GSZ may block mast cell degranulation by inhibiting the TLR4/MyD88/NF-κB p65 pathway and thus influence rheumatoid arthritis onset.Conclusion:Taken together,our data suggested that GSZ may be a promising therapeutic decoction for the prophylactic treatment of rheumatoid arthritis.
基金National Key Research and Development Program of China(No.2018YFC1705503).
文摘Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.
