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.

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.

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.

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.

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.

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.

Changes in renal function and morphological variations of kidney diseases in rheumatoid arthritis patients

Objective:Rheumatoid nephropathy is one of the most severe extra-articular manifestations of rheumatoid arthritis(RA)associated with a very unfavorable prognosis.This study aimed to identify changes in renal function and morphological variations of kidney diseases in RA patients.Methods:The study enrolled patients(126 patients)between 18 and 55 years of age with a confirmed active RA of more than 12 months.Each patient underwent the following range of laboratory and instrumental research methods:general clinical analysis of blood and urine,performing urinalysis according to Nechiporenko method;determining daily proteinuria;determining the blood content of glucose,urea,creatinine,uric acid,total bilirubin,liver transaminase level,ionogram,lipidogram,and coagulogram;determining the blood content of rheumatoid factor,anti-streptolysin O,and C-reactive protein;and X-ray of the joints of hands and feet.Renal function was examined by estimating glomerular filtration rate,tubular reabsorption index,and renal functional reserve.For studying the morphological changes in the kidneys under ultrasound examination,renal biopsy was performed in 31 patients with RA with urinary syndrome(proteinuria more than 0.3 g per day and hematuria).Results:Nephropathy in RA is characterized by impaired renal function and manifested by an increased blood creatinine and a decrease in glomerular filtration rate and renal functional reserve.Among morphological variations of nephropathy at RA,mesangial proliferative glomerulonephritis prevails,accounting for 48.4%of patients.Other disorders include the secondary amyloidosis(29.0%of patients),tubulointerstitial nephritis(16.1%),membranous glomerulonephritis(3.2%),and focal-segmental glomerulosclerosis(3.2%).Conclusion:Kidney damage is a common systemic manifestation of RA with a long and active course,a major nephropathy trigger.

Case Report: Rhupus (The Association of Systemic Lupus Erythematosus and Rheumatoid Arthritis): About 2 Cases

Introduction: The association of systemic lupus erythematosus and rheumatoid arthritis (rhupus) is a rare clinical condition. Throughout the world, 287 cases of Rhupus have been described. We report two new observations of two patients who presented predominantly distal erosive polyarthritis with positive anti-Sm antibodies in one case and SmRNP in the other case. Observations: Case 1: 37 years old patient, with a recent diagnosis of pulmonary tuberculosis. She has since 8 months an inflammatory, bilaterally and symmetrical polyarthralgia without deformation or ankylosing synovitis, associated with malar erythema without other abnormalities. Immunological tests showed: positive Rheumatoid factor at 158 IU/ml, positive Anti-CCP at 550 IU/ml, and positivity of antinuclear at 1/1280 nuclear fluorescence with a strong presence of anti-Sm >8 IU/ml. The diagnosis of rhupus was concluded, without serious visceral involvement. Case 2: A 28-year-old patient, married with 3 children, with bilateral, symmetrical, deforming and chronic polyarthritis affecting large and small joints, which had been evolving for over 5 years without cutaneous abnormality associated. Paraclinical investigations showed: a biological inflammatory syndrome. Immunology was positive, with rheumatoid factors at 78 IU/ml, anti-CCP at 561 IU/ml, antinuclear antibodies at 1/1280 with positive anti-SmRNP and anti-SSA/Ro52, and a positive direct Coombs test. Joint ultrasound revealed tenosynovitis of the extensors and common flexors of the fingers, erosions and synovitis of multiple PPIs. The diagnosis of rhupus was based on the presence of 10 ACR criteria for RA and 8 ACR/EULAR 2019 criteria for SLE. Conclusion: Rheumatoid arthritis is a rare autoimmune disease combining features of both systemic lupus erythematosus and rheumatoid arthritis in the same patient, often sequentially. Despite a growing number of case reports and series, a consensus on the classification of SLE arthritis is still lacking, and diagnostic criteria for rhupus do not exist. These cases of rhupus must be recognized, as the vital and/or functional prognosis may be different from SLE alone or isolated RA.

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.

Correlation Study Between T Lymphocyte Subsets and Rheumatoid Arthritis

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.

Research progress of local characteristic drugs for treatment of rheumatoid arthritis in Xinjiang

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.

Effect of N-Acetylcysteine Combined with Lung Rehabilitation Therapy on Exercise Endurance and Quality of Life of Patients with Rheumatoid Arthritis-Related Interstitial Lung Disease

Objective:To explore the effect of N-acetylcysteine combined with lung rehabilitation therapy on exercise endurance and quality of life in patients with rheumatoid arthritis-related interstitial lung disease(RA-ILD).Methods:Fifty-six patients with RA-ILD admitted to Xijing Hospital from May 2022 to January 2024 were randomly divided into two groups:a non-rehabilitation group and a pulmonary rehabilitation group,with 28 patients in each group.Both groups received routine treatment.Additionally,the non-rehabilitation group received N-acetylcysteine treatment,while the lung rehabilitation group received lung rehabilitation treatment in addition to N-acetylcysteine.The improvement in exercise endurance and dyspnea between the two groups after treatment was compared and the quality of life of the patients was observed.Results:After treatment,the exercise endurance score in the lung rehabilitation group(335.67±45.29)was higher than that in the non-rehabilitation group(P<0.05).The dyspnea score in the lung rehabilitation group(0.72±0.16)was lower than that in the non-rehabilitation group(P<0.05).Additionally,FVC(3.18±0.58 L),FEV1(2.28±0.56 L),FEV1/FVC(69.69±5.56),and DLCO(60.53±5.92 mL/mmHg/min)were higher in the lung rehabilitation group compared to the non-rehabilitation group after treatment(P<0.05).Conclusion:Lung rehabilitation therapy combined with N-acetylcysteine treatment can effectively improve dyspnea symptoms,lung function,and exercise endurance in patients with RA-ILD.This approach helps to improve patient’s quality of life and is beneficial for their prognosis.

Systematic review and network meta-analysis of different nonsteroidal anti-inflammatory drugs for juvenile idiopathic arthritis

BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.

Major depressive disorders in patients with inflammatory bowel disease and rheumatoid arthritis

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.

An intra-articular injectable phospholipids-based gel for the treatment of rheumatoid arthritis

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.

Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis

Flare and multiple recurrences pose significant challenges in gouty arthritis.Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences.It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis,calling for therapeutic systems to achieve these two goals simultaneously.In this study,we propose a biomimetic integrated nanozyme,HMPB-Pt@MM,comprising platinum nanozyme and hollow Prussian blue.It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages.Additionally,it rapidly targets inflamed ankles through the camouflage of macrophage membranes.Furthermore,HMPB-Pt@MM exhibits urate oxidase-like capabilities,continuously metabolizing locally elevated uric acid concentrations,ultimately inhibiting multiple recurrences of gouty arthritis.In summary,HMPB-Pt@MM integrates ROS clearance with uric acid metabolism,offering a promising platform for the treatment of gouty arthritis.