Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of Tripterygium Glycosides Tablets Against Rheumatoid Arthritis

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.

Novel Assessment Technique: Ring Gauge Measurement of Finger Joint Circumference Changes in Patients with Rheumatoid Arthritis

Objectives: As therapeutic modalities for rheumatoid arthritis (RA) advance, immediate and quantitative determination of RA disease status is becoming increasingly important. The purpose of this study was to validate the usefulness of a ring gauge as a simple semiquantitative method for assessing hand swelling in patients with RA. Methods: We enrolled patients diagnosed with RA either initiated or switched to a biological therapeutic agent. The circumference of the interphalangeal (IP) joint and the proximal interphalangeal (PIP) joint was measured using a ring gauge. Assessments of the joint echocardiography, incorporating both Gray Scale (GS) and Power Doppler (PD) imaging, were conducted. These evaluations were performed both before the initiation of biological agent treatment and 28 days after the initial dose. Results: Following the treatment intervention, a significant reduction was observed in the circumference of the joint from the thumb to the little finger (p Conclusions: Our study demonstrated the effectiveness of using a ring gauge as a simple assessment tool for RA, revealing that a change in the ring gauge number by 2 or more corresponded to either improvement or deterioration in synovial thickening detected via joint echocardiography.

Attenuation of the Activation of NLRP3 Inflammasome in Fibroblast Like Synoviocytes of Rheumatoid Arthritis by Baicalin through Regulating the Let-7i-3p/PI3K/Akt/NF-κB Signaling Axis

[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.

Effect of Yangqixue Qufengshi Recipe (养气血祛风湿方) on Rheumatoid Arthritis Model Mice under Different Genetic Backgrounds

Objective： To study the effect of Yangqixue Qufengshi Recipe （养气血祛风湿方, YQXQFS） on rheumatoid arthritis （RA） model mice under different genetic backgrounds. Methods： Collagen Induced Arthritis （CIA） were established on HLA-DR4 transgenic （TG） mice and non-transgenic （NTG） mice, which partly were raised with YQXQFS, and the onset day of CIA, the level of type Ⅱ collagen （C Ⅱ ）-reactive antibodies and the pathological scores of CIA were assessed. Results： Under HLA-DR4 TG background （compared with NTG mice）, the earlier onset day of CIA （ 11.22±3.35 days vs 16.56 ±4.75 days, P〈0.05） and higher level of C Ⅱ-reactive antibodies （0. 2274±0. 1390μg/ml vs 0.1101±0. 0560μg/ml, P〈0.05） were observed, but the pathological scores of CIA remained unchange. YQXQFS could not influence the onset day of CIA and the level of C Ⅱ-reactive antibodies, but had a certain effect on the total pathological scores （6.56±3.43 scores vs 11.11±5.64 scores） and bone erosion （0.22±0.44 scores vs 1.67±1.50 scores） of CIA on NTG mice （P〈0.05）, NTG YQXQFS group compared with NTG experimental group. Conclusion： YQXQFS had a certain effect on RA model, but had no significant effect on HLA-DR4 related CIA.

Rare Association between Chronic Tophaceous Gout and Rheumatoid Arthritis in a Black African Subject: A Case Report

Rheumatoid arthritis (RA) and gout are common diseases, but their coexistence is rare. We describe the case of a 76-year-old man with hypertension who had been treated for gout for 20 years on allopurinol and colchicine. He was seen in consultation for deforming polyarthritis of the small and large joints, which had been evolving for about 2 years. The acute episode occurred 10 days earlier with the onset of bilateral and symmetrical polyarthritis affecting the large and small joints. The physical examination revealed a peripheral joint syndrome with ulnar gale force deformities of the hands and several buttonhole deformities of the fingers. In addition, there were nodules, some of which were fistulised, giving rise to a chalky slurry. The biology revealed an inflammatory syndrome in addition to rheumatoid factors and ACPA, which were elevated. Biological analysis of the nodular fluid revealed clusters of sodium urate crystals and ultrasound scans of the joints revealed a double-contour appearance in several joints. The diagnosis of RA was made using the 2010 ACR/EULAR criteria. The patient was treated as an outpatient with corticosteroids before being put on methotrexate. It is important to understand that these two conditions can occur at the same time, so it is important to consider them when treating patients with gout or RA.

Antibodies to Tumor Necrosis Factors in the Treatment of Rheumatoid Arthritis and Spondyloarthritis: The Basic Science, Clinical Science and Unmet Needs;Results from a Single Center

Inflammatory rheumatological diseases like rheumatoid arthritis (RA) and ankylosing spondylitis/Spondyloarthritis (AS/SpA), have been treated with NSAIDs (non steroidal anti-inflammatory drugs), corticosteroids, and DMARDs (disease modifying anti-rheumatic drugs).These have been only partially effective for the management of symptoms, since they are rarely associated with the complete control of disease and rarely slow down radiological damage. Several cytokines have been implicated in the pathogenesis of the inflammation and tumor necrosis factor (TNF) is the most important. The last decade and a half has seen advances in the form of “anti-TNF” therapies for RA and AS/SpA patients which target and neutralize the TNF cytokines, and thus reduce the disease activity. Two anti-TNF therapies have been used in India for treating DMARD resistant RA and AS/SpA for the last 13 years;Infliximab and Etanercept respectively. This paper is a description of the clinical outcomes and unmet needs/toxicities associated with the treatment of RA and AS/SpA with anti-TNF therapies (Infliximab, Etanercept), at a single rheumatology center (tertiary care, super-specialty hospital, Indraprastha Apollo Hospitals, New Delhi) in north India.

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

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.

Development of biomedical hydrogels for rheumatoid arthritis treatment

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.

Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment

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.

Crossroads:Pathogenic role and therapeutic targets of neutrophil extracellular traps in rheumatoid arthritis

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.

Reconstructive Surgery in Patients with Rheumatoid Arthritis

Objective: The aim of this research was to find out if reconstructive surgery is the best option to improve the quality of life of patients with rheumatoid arthritis compared to other monotherapy or combination therapy treatments.Methods: The research uses a mixed qualitative-quantitative, correlational, and cross-sectional approach. The medical records of a sample of 28 patients with rheumatoid arthritis who were treated at Rio Hospital in Riobamba-Ecuador in the period 2022-2024 were reviewed. The Health Assessment Questionnaire (HAQ) was used to assess quality of life, and the Diseases Activity Score (DAS) 28 was used to measure the degree of joint involvement. To establish the correlation between variables, HJ Biplot multivariate analysis was applied in RStudio. Results: A high correlation was found between quality of life and the degree of joint involvement DAS 28, patients with a degree of high activity (more unfavorable condition) have a worse quality of life due to their severe disability. Both quality of life and the degree of joint involvement were also correlated with the treatment they receive, patients with worse quality of life and a higher degree of joint involvement received combined therapy as treatment. Patients who have undergone reconstructive surgery have a better quality of life. Overweight patients tend to have greater joint involvement and poorer quality of life. Conclusions: The results suggest that reconstructive surgery plays an important role in the management of patients with advanced rheumatoid arthritis, helping to restore function and improve quality of life.

Concomitant atypical knee gout and seronegative rheumatoid arthritis:A case report

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.

Anti-inflammatory Effect of Polysaccharide from Embelia parviflora Wall.on Rheumatoid Arthritis in Rats

[Objectives]To investigate the anti-inflammatory effect of Embelia parviflora Wall.polysaccharide on rheumatoid arthritis(RA)in rats.[Methods]RA rat model was induced by type II collagen.After successful modeling,the rats were divided into model group,positive group,low,medium and high dose of E.parviflora Wall.polysaccharide groups,and normal control group.Body mass,toe volume and arthritis index were measured,and thymus index and spleen index were calculated.The levels of interleukin-1β,interleukin-6 and tumor necrosis factor-αin serum and synovial tissue of ankle joint were detected by ELISA.[Results]Compared with the normal control group,the pathological changes such as synovial hyperplasia and unclear layer were observed in the model group,the body mass was decreased(P<0.05),the toe volume,arthritis index,thymus and spleen index were increased(P<0.05),and the levels of IL-1β,IL-6 and TNF-αin serum and ankle synovial tissue were increased(P<0.05).Compared with the model group,the histopathological changes in synovium of ankle joint in the positive group and the medium and high dose groups of E.parviflora Wall.polysaccharide were significantly improved,and the body mass was increased(P<0.05).The toe volume,arthritis index,thymus index and spleen index were decreased(P<0.05).The levels of IL-Iβ,IL-6 and TNF-αin serum and synovial tissue of ankle joint were increased(P<0.05),while there was no significant difference between the low dose group of E.parviflora Wall.polysaccharide and the model group(P>0.05).[Conclusions]E.parviflora Wall.polysaccharide can reduce the body's inflammatory response and improve RA,which may be related to the inhibition of the activation of inflammatory cytokines IL-1β,IL-6 and TNF-α.

Drug Survival of Biological Therapy in Patients with Rheumatoid Arthritis

Background: Biological therapy prevents structural damage, improves functional capacity, and has provided an important advance in the treatment of rheumatoid arthritis (RA). In a real-life scenario, drug survival is an indirect measure of the efficacy, safety, and tolerability of a drug. The objective of the study was to analyze the drug survival rate of biological therapy in a national health system (SUS). Methods: A retrospective cohort study of the medication process of RA was carried out in public pharmacies of a Brazilian state from January 2010 to April 2017. The Kaplan-Meier survival analysis was applied. The survival rate was defined as the incidence of drug discontinuation. The retention rate was defined as the mean of months using the drug. Results: Of the total of 902 individuals, 83.6% were female with a mean age of 56 years. Anti-TNF, mostly adalimumab (ADA), was the main biological agent prescribed. Mean drug retention of the first biological was 59.6 months (95% CI: 56.7 - 62.5), followed by 53.7 (95% CI: 48 - 59.4) and 28.2 (95% CI: 23.1 - 23.3) months for the second and third biologicals, respectively. Among the anti-TNF group, ADA, ETN, IFX had the better retention rate. There was no statistical difference in the general survival analyses (p = 0.18) among the groups. However, along the first 2 years, ADA, ETN, and RTX had the three better drug survival. The drug retention seems to increase with age (p = 0.036), with the subgroups > 70 years of age having the highest means (70 - 80 years: 67.29;>80: 67.53). Among all, 27.1% of patients switched to a second biologic. Conclusion: The anti-TNF group, mostly adalimumab (ADA), is the most prescribed medication as first and second-line therapy, reflecting its accessibility in the SUS and efficiency of the follow-up protocols. Among the anti-TNF group, ADA, ETN, and IFX had the better retention rate. Additionally, ADA and ETN had the better drug survival for the first treatment in the first 2 years. RTX was the non-anti-TNF with the best survival. A quarter of patients who start a biological therapy fail and switch to another drug (27%).

Carrier-free nanodrugs for rheumatoid arthritis treatment

Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current rheumatic therapy drugs such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,or biologics are remarkably restricted by their poor blood circulation capability,unsatisfied drug loading efficiency,off-target irritation,and carrier-related toxicity.Recently,great efforts have concentrated on carrier-free nanoparticulated delivery strategy,and multifarious carrier-free nanodrugs including nanocrystal,nanoparticle,and nanomicelle have been manifested to possess boosted stability,extended circulation capability,enhanced drug accumulation at the inflammatory joint,and high-efficiency and low-toxicity therapeutic outcomes in RA models.Hence,this review provides a comprehensive summary of carrier-free nanodrugs for efficient RA treatment,with an emphasis on nanocrystal,nanoparticle,and nanomicelle,and then the ongoing challenges and prospects of carrier-free nanodrugs are discussed.

Interleukin 6 and Bone Erosions in Rheumatoid Arthritis in an African Hospital

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.

Evaluating the influence of a structured nursing protocol on targeted outcomes in rheumatoid arthritis patients

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.

Traditional Chinese Medicine as a Treatment for Rheumatoid Arthritis:From Empirical Practice to Evidence-Based Therapy

Rheumatoid arthritis(RA)is a common autoimmune condition with an elusive etiology.Conventional and biological disease-modifying drugs sometimes fail or produce only partial responses.Traditional Chinese medicine(TCM)has long been used in China as a treatment for RA and is achieving everincreasing acceptance worldwide.TCM treatments are traditionally guided by the theory of treatment based on TCM syndrome differentiation;however,they remain a matter of empirical practice relying on TCM theories and doctors’own experience,which places severe restrictions on worldwide TCM application.Nevertheless,TCM is a treasure trove for drug discovery,particularly as a treatment for complicated human conditions.The discoveries of artemisinin as a treatment for malaria and of TCM–arsenic trioxide(As2O3)combination therapy as a treatment for acute promyelocytic leukemia(APL)are excellent examples of the great value of TCM.Regarding RA treatments,many Chinese medicinal herbs and their formulas,extracts,ingredients,and even single compounds have been used in clinical applications.Several Chinese proprietary medicines(CPMs)derived from TCM formulas or herbal bioactive components,such as the controlled-release ZhengQingFengTongNing(ZQFTN)Tablets,Tripterygium Glycoside Tablets,and Total Glucosides of Peony(TGP)Capsules,have been included in the National Health Insurance Directory of China,and show comparable therapeutic efficacies to those of western chemical drugs with fewer side effects.As TCM research has advanced,particularly in the use of multidisciplinary technologies,the scientific foundations and characteristics of the use of TCM to treat RA have been revealed,and the quality of TCM treatments have been increasingly enhanced.However,TCM generally lacks sufficient clinical and laboratory data to be consistent with international standards for quality,safety,and efficacy in order to support its application worldwide.Therefore,intensive basic and clinical studies on TCM are required.In particular,investigations that use cutting-edge technologies in analytical chemistry,biology,and biomedical sciences,and the development of randomized clinical trials(RCTs)and personalized pragmatic randomized controlled trials(PPRCTs)are necessary.Researchers should also collaborate to advance TCM from empirical practice to evidence-based therapy,thus consistently promoting TCM development and globalization in a vital,beneficial,and contributable manner.

Correlation Analysis Between Changes of D-Dimer Level and Rheumatoid Arthritis Complicated with Interstitial Lung Disease

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.

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis:study protocol of a multicenter randomized controlled trial

BACKGROUND： Rheumatoid arthritis （RA）, as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA. METHODS AND DESIGN： This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1：1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo （imitation leflunomide）. The control group will receive leflunomide and an herbal placebo （imitation Xinfeng Capsule）. The American College of Rheumatology （ACR） Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate （ACR20）, which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment. DISCUSSION： The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is N CT01774877.