[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
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 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 an...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.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
Background: Acute lymphoblastic leukemia (ALL), the most common paediatric malignancy, is a heterogeneous hematologic disease. ALL patients may present with isolated and persistent osteo-articular complaints, lower in...Background: Acute lymphoblastic leukemia (ALL), the most common paediatric malignancy, is a heterogeneous hematologic disease. ALL patients may present with isolated and persistent osteo-articular complaints, lower incidence of hepatomegaly, splenomegaly or lymphadenopathy without clear laboratory features, and misdiagnosed as systemic juvenile idiopathic arthritis (sJIA). Methods: This was a single center cross sectional study over a period of 4 years. Clinic laboratory profiles of 39 ALL children were compared with 39 age and sex-matched sJIA cases. Result: Among 39 ALL patients 89.7% were initially misdiagnosed as sJIA upon clinical presentation. Majority (66.7%) of ALL patients had oligo-articular joint involvement. In sJIA, small joints of the hands were most commonly involved. The total WBC count was significantly higher in ALL patients (p-value 0.0065). CRP and LDH values between the two groups showed significant differences (p-value 0.00006 and 0.00001 respectively). Conclusion: The presentation of leukemia with arthralgia or arthritis makes the diagnosis difficult for the physicians. The diagnosis of sJIA must be made with caution keeping the possibility of haematological malignancy in mind.展开更多
BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The informat...BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.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
BACKGROUND Pancreatitis,panniculitis,and polyarthritis(PPP)syndrome is a rare form of pancreatic disease.It is characterized by bullous erythematous skin lesions and arthritis,and both are triggered by pancreatic malf...BACKGROUND Pancreatitis,panniculitis,and polyarthritis(PPP)syndrome is a rare form of pancreatic disease.It is characterized by bullous erythematous skin lesions and arthritis,and both are triggered by pancreatic malfunction.Few cases have been described in the literature thus far.Due to the inconsistency in its clinical presentation,its diagnosis can be a challenge.Early therapy initiation is essential to reduce mortality;however,there is currently no gold standard for treatment.CASE SUMMARY A 66-year-old polymorbid male patient presented with several superficial abscesses on both lower legs and painful swelling in the knee.Treatment for septic arthritis and septic skin infection over several weeks failed.His general condition deteriorated gradually and worsened with sudden onset of abdominal pain.A diagnosis of necrotizing pancreatitis was made.He subsequently underwent a laparotomy and drainage of the pancreas.Eventually,our patient improved,and his abdominal complaints,knee pain,and dermal lesions resolved.CONCLUSION PPP syndrome is rare and easily misdiagnosed,as abdominal symptoms may be delayed or absent.Clinicians should consider PPP syndrome if they encounter refractory panniculitis in combination with joint infection.展开更多
RNA interference(RNAi)using small interfering RNA(siRNA)has shown potential as a therapeutic option for the treatment of arthritis by silencing specific genes.However,siRNA delivery faces several challenges,including ...RNA interference(RNAi)using small interfering RNA(siRNA)has shown potential as a therapeutic option for the treatment of arthritis by silencing specific genes.However,siRNA delivery faces several challenges,including stability,targeting,off-target effects,endosomal escape,immune response activation,intravascular degradation,and renal clearance.A variety of nanotherapeutics like lipidic nanoparticles,liposomes,polymeric nanoparticles,and solid lipid nanoparticles have been developed to improve siRNA cellular uptake,protect it from degradation,and enhance its therapeutic efficacy.Researchers are also investigating chemical modifications and bioconjugation to reduce its immunogenicity.This review discusses the potential of siRNA nanotherapeutics as a therapeutic option for various immune-mediated diseases,including rheumatoid arthritis,osteoarthritis,etc.siRNA nanotherapeutics have shown an upsurge of interest and the future looks promising for such interdisciplinary approach-based modalities that combine the principles of molecular biology,nanotechnology,and formulation sciences.展开更多
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 colchici...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.展开更多
Background: Rheumatoid arthritis is a systemic inflammatory arthritis characterized by joint pain and morning stiffness. The affected joints are typically symmetrically affected, and given the inflammatory nature of t...Background: Rheumatoid arthritis is a systemic inflammatory arthritis characterized by joint pain and morning stiffness. The affected joints are typically symmetrically affected, and given the inflammatory nature of this condition, patients often present with warmth and erythema around affected joints as well as fatigue. Extra-articular manifestations, especially pleuro-pericardial inflammation, are rare initial presentations, although may be seen in advanced or undertreated disease. Case Presentation: We describe a case of a rheumatoid arthritis presenting atypically in a middle-aged male who came to the emergency department complaining of diffuse muscle pain and swelling in the distal extremities. Cardiac ultrasound revealed pleuro-pericardial inflammation and effusions. Myositis and infectious causes were ruled out and bilateral hand x-rays did not show erosions or any evidence of arthritic changes. All rheumatological auto-antibodies were negative except for rheumatoid factor and anti-cyclic citrullinated peptide (CCP) and a diagnosis of rheumatoid arthritis was made. The patient was started on prednisone with excellent response. Conclusions: This case highlights that rheumatoid arthritis can uncommonly present initially with extra-articular manifestations that are often manifested in advanced disease. Typically, extra-articular manifestations, especially those as severe as this patient’s, occur with untreated, advanced disease and could accompany extensive arthritic joint changes. Thus, it is important to have an understanding of rare, atypical presentations of rheumatoid arthritis so that a high index of suspicion can be maintained to make the diagnosis and initiate treatment in a timely manner.展开更多
Post-traumatic osteoarthritis(PTOA)is a complex and painful problem in the foot and ankle.Ninety percent of osteoarthritis cases in the foot and ankle can be classified as post-traumatic.PTOA can affect any of the 33 ...Post-traumatic osteoarthritis(PTOA)is a complex and painful problem in the foot and ankle.Ninety percent of osteoarthritis cases in the foot and ankle can be classified as post-traumatic.PTOA can affect any of the 33 joints in the foot and the ankle.Distraction arthroplasty is a method for treatment of early arthritic joints without fusing or replacing them and its effectiveness has been well documented.The purpose of this case series is to present our successful experiences and positive results using distraction arthroplasty to treat PTOA in the ankle,subtalar,first metatarsophalangeal,and second tarsometatarsal joints,and to present distraction arthroplasty as a viable alternative to invasive joint sacrificing procedures such as arthrodesis or arthroplasty.Distraction Arthroplasty effectively and safely treats PTOA and improves the stability of joints in the Foot and Ankle.Additionally,the use of bone marrow aspirate concentrate as an adjuvant can improve the long-term functional and structural outcomes of the joint,and can prolong the need for further,more aggressive surgical interventions such as fusion or arthroplasty.展开更多
BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established...BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.展开更多
Objective:To explore the effect of Cassia fistula on collagenⅡ-induced arthritis in rats.Methods:The effect of 250 and 500 mg/kg chloroform and hydroalcoholic extract of Cassia fistula leaf on collagenⅡ-induced arth...Objective:To explore the effect of Cassia fistula on collagenⅡ-induced arthritis in rats.Methods:The effect of 250 and 500 mg/kg chloroform and hydroalcoholic extract of Cassia fistula leaf on collagenⅡ-induced arthritis was investigated by evaluating paw volume,arthritis index,spleen index,and biochemical parameters.Histopathological analysis and docking study were also performed.Results:A dose-dependent reduction in paw volume,arthritic index,and spleen index was observed following oral administration of the chloroform and hydroalcoholic extracts.Treatment with Cassia fistula extracts reduced tumor necrosis factor-α,interleukin(IL)-1β,IL-6,prostaglandin E_(2),aspartate aminotransferase,alanine aminotransferase,total leucocyte count,and erythrocyte sedimentation rate while increasing IL-10 level.In addition,Cassia fistula extracts improved joint architecture,and prevented cartilage and bone destruction.Docking analysis demonstrated that the physcion,1-octacosanol,5,3’,4’-trihydroxy-6-methoxy-7-O-α-Lrhamnopyranosyl-(1,2)-O-β-D-galactopyranoside and scopoletin may be responsible for the anti-arthritic effect of Cassia fistula.Conclusions:Cassia fistula suppresses the progression of collagenⅡ-induced arthritis by lowering the inflammatory factors,decreasing paw volume and arthritic index,and alleviating joint architecture.However,further studies are required to confirm the bioactive molecule responsible for the anti-arthritic potential of Cassia fistula.展开更多
Objective:To investigate the anti-inflammatory and analgesic effects of Solanum procumbens on complete Freund’s adjuvantinduced arthritis rat models.Methods:We isolated and identified five compounds in the ethanolsol...Objective:To investigate the anti-inflammatory and analgesic effects of Solanum procumbens on complete Freund’s adjuvantinduced arthritis rat models.Methods:We isolated and identified five compounds in the ethanolsoluble Solanum procumbens extract(SP)with anti-inflammatory effects,including ursolic acid,β-sitosterol,hexadecanoic acid,cisvaccenic acid,and vanillic acid.Additionally,we investigated the anti-inflammatory effects of SP on rheumatoid arthritis symptoms,including paw volumes,local temperatures,withdrawal latency,and mechanical withdrawal threshold at the hind paw and white blood cell(WBC)number from complete Freund’s adjuvant-induced arthritis rat models.Results:We have successfully established a complete Freund’s adjuvant-induced arthritis rat model at a low dose(1 mg/mL).SP extract significantly reduced paw volumes(P<0.05),prolonged withdrawal latencies(P<0.05),decreased local temperature,and increased the mechanical withdrawal threshold(P<0.05),but only SP extract at the dose of 300 mg/kg significantly decreased WBC numbers.Conclusions:SP extract could be a potential medication candidate with anti-inflammatory effects for arthritis,but it requires further investigation into the mechanism of the SP and its effectiveness on other models as well as clinical trials.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
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(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.
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 the Science and Technology Plan Project of Jingmen Science and Technology Bureau,No.2018YFZD025。
文摘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.
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Background: Acute lymphoblastic leukemia (ALL), the most common paediatric malignancy, is a heterogeneous hematologic disease. ALL patients may present with isolated and persistent osteo-articular complaints, lower incidence of hepatomegaly, splenomegaly or lymphadenopathy without clear laboratory features, and misdiagnosed as systemic juvenile idiopathic arthritis (sJIA). Methods: This was a single center cross sectional study over a period of 4 years. Clinic laboratory profiles of 39 ALL children were compared with 39 age and sex-matched sJIA cases. Result: Among 39 ALL patients 89.7% were initially misdiagnosed as sJIA upon clinical presentation. Majority (66.7%) of ALL patients had oligo-articular joint involvement. In sJIA, small joints of the hands were most commonly involved. The total WBC count was significantly higher in ALL patients (p-value 0.0065). CRP and LDH values between the two groups showed significant differences (p-value 0.00006 and 0.00001 respectively). Conclusion: The presentation of leukemia with arthralgia or arthritis makes the diagnosis difficult for the physicians. The diagnosis of sJIA must be made with caution keeping the possibility of haematological malignancy in mind.
基金Supported by the Ministry of Science and Higher Education of the Russian Federation,No.075-15-2022-301.
文摘BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.
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BACKGROUND Pancreatitis,panniculitis,and polyarthritis(PPP)syndrome is a rare form of pancreatic disease.It is characterized by bullous erythematous skin lesions and arthritis,and both are triggered by pancreatic malfunction.Few cases have been described in the literature thus far.Due to the inconsistency in its clinical presentation,its diagnosis can be a challenge.Early therapy initiation is essential to reduce mortality;however,there is currently no gold standard for treatment.CASE SUMMARY A 66-year-old polymorbid male patient presented with several superficial abscesses on both lower legs and painful swelling in the knee.Treatment for septic arthritis and septic skin infection over several weeks failed.His general condition deteriorated gradually and worsened with sudden onset of abdominal pain.A diagnosis of necrotizing pancreatitis was made.He subsequently underwent a laparotomy and drainage of the pancreas.Eventually,our patient improved,and his abdominal complaints,knee pain,and dermal lesions resolved.CONCLUSION PPP syndrome is rare and easily misdiagnosed,as abdominal symptoms may be delayed or absent.Clinicians should consider PPP syndrome if they encounter refractory panniculitis in combination with joint infection.
文摘RNA interference(RNAi)using small interfering RNA(siRNA)has shown potential as a therapeutic option for the treatment of arthritis by silencing specific genes.However,siRNA delivery faces several challenges,including stability,targeting,off-target effects,endosomal escape,immune response activation,intravascular degradation,and renal clearance.A variety of nanotherapeutics like lipidic nanoparticles,liposomes,polymeric nanoparticles,and solid lipid nanoparticles have been developed to improve siRNA cellular uptake,protect it from degradation,and enhance its therapeutic efficacy.Researchers are also investigating chemical modifications and bioconjugation to reduce its immunogenicity.This review discusses the potential of siRNA nanotherapeutics as a therapeutic option for various immune-mediated diseases,including rheumatoid arthritis,osteoarthritis,etc.siRNA nanotherapeutics have shown an upsurge of interest and the future looks promising for such interdisciplinary approach-based modalities that combine the principles of molecular biology,nanotechnology,and formulation sciences.
文摘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.
文摘Background: Rheumatoid arthritis is a systemic inflammatory arthritis characterized by joint pain and morning stiffness. The affected joints are typically symmetrically affected, and given the inflammatory nature of this condition, patients often present with warmth and erythema around affected joints as well as fatigue. Extra-articular manifestations, especially pleuro-pericardial inflammation, are rare initial presentations, although may be seen in advanced or undertreated disease. Case Presentation: We describe a case of a rheumatoid arthritis presenting atypically in a middle-aged male who came to the emergency department complaining of diffuse muscle pain and swelling in the distal extremities. Cardiac ultrasound revealed pleuro-pericardial inflammation and effusions. Myositis and infectious causes were ruled out and bilateral hand x-rays did not show erosions or any evidence of arthritic changes. All rheumatological auto-antibodies were negative except for rheumatoid factor and anti-cyclic citrullinated peptide (CCP) and a diagnosis of rheumatoid arthritis was made. The patient was started on prednisone with excellent response. Conclusions: This case highlights that rheumatoid arthritis can uncommonly present initially with extra-articular manifestations that are often manifested in advanced disease. Typically, extra-articular manifestations, especially those as severe as this patient’s, occur with untreated, advanced disease and could accompany extensive arthritic joint changes. Thus, it is important to have an understanding of rare, atypical presentations of rheumatoid arthritis so that a high index of suspicion can be maintained to make the diagnosis and initiate treatment in a timely manner.
文摘Post-traumatic osteoarthritis(PTOA)is a complex and painful problem in the foot and ankle.Ninety percent of osteoarthritis cases in the foot and ankle can be classified as post-traumatic.PTOA can affect any of the 33 joints in the foot and the ankle.Distraction arthroplasty is a method for treatment of early arthritic joints without fusing or replacing them and its effectiveness has been well documented.The purpose of this case series is to present our successful experiences and positive results using distraction arthroplasty to treat PTOA in the ankle,subtalar,first metatarsophalangeal,and second tarsometatarsal joints,and to present distraction arthroplasty as a viable alternative to invasive joint sacrificing procedures such as arthrodesis or arthroplasty.Distraction Arthroplasty effectively and safely treats PTOA and improves the stability of joints in the Foot and Ankle.Additionally,the use of bone marrow aspirate concentrate as an adjuvant can improve the long-term functional and structural outcomes of the joint,and can prolong the need for further,more aggressive surgical interventions such as fusion or arthroplasty.
文摘BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.
基金supported by the Institute of Pharmaceutical Sciences,Kurukshetra University,Kurukshetra,Haryana,India,and Govt.College of Pharmacy,Rohru,District Shimla,Himachal Pradesh,India。
文摘Objective:To explore the effect of Cassia fistula on collagenⅡ-induced arthritis in rats.Methods:The effect of 250 and 500 mg/kg chloroform and hydroalcoholic extract of Cassia fistula leaf on collagenⅡ-induced arthritis was investigated by evaluating paw volume,arthritis index,spleen index,and biochemical parameters.Histopathological analysis and docking study were also performed.Results:A dose-dependent reduction in paw volume,arthritic index,and spleen index was observed following oral administration of the chloroform and hydroalcoholic extracts.Treatment with Cassia fistula extracts reduced tumor necrosis factor-α,interleukin(IL)-1β,IL-6,prostaglandin E_(2),aspartate aminotransferase,alanine aminotransferase,total leucocyte count,and erythrocyte sedimentation rate while increasing IL-10 level.In addition,Cassia fistula extracts improved joint architecture,and prevented cartilage and bone destruction.Docking analysis demonstrated that the physcion,1-octacosanol,5,3’,4’-trihydroxy-6-methoxy-7-O-α-Lrhamnopyranosyl-(1,2)-O-β-D-galactopyranoside and scopoletin may be responsible for the anti-arthritic effect of Cassia fistula.Conclusions:Cassia fistula suppresses the progression of collagenⅡ-induced arthritis by lowering the inflammatory factors,decreasing paw volume and arthritic index,and alleviating joint architecture.However,further studies are required to confirm the bioactive molecule responsible for the anti-arthritic potential of Cassia fistula.
基金supported by Military Hospital 103Vietnam Military Medical University。
文摘Objective:To investigate the anti-inflammatory and analgesic effects of Solanum procumbens on complete Freund’s adjuvantinduced arthritis rat models.Methods:We isolated and identified five compounds in the ethanolsoluble Solanum procumbens extract(SP)with anti-inflammatory effects,including ursolic acid,β-sitosterol,hexadecanoic acid,cisvaccenic acid,and vanillic acid.Additionally,we investigated the anti-inflammatory effects of SP on rheumatoid arthritis symptoms,including paw volumes,local temperatures,withdrawal latency,and mechanical withdrawal threshold at the hind paw and white blood cell(WBC)number from complete Freund’s adjuvant-induced arthritis rat models.Results:We have successfully established a complete Freund’s adjuvant-induced arthritis rat model at a low dose(1 mg/mL).SP extract significantly reduced paw volumes(P<0.05),prolonged withdrawal latencies(P<0.05),decreased local temperature,and increased the mechanical withdrawal threshold(P<0.05),but only SP extract at the dose of 300 mg/kg significantly decreased WBC numbers.Conclusions:SP extract could be a potential medication candidate with anti-inflammatory effects for arthritis,but it requires further investigation into the mechanism of the SP and its effectiveness on other models as well as clinical trials.
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.
