Objective:To compare the efficiency and purity of exosomes extracted from synovial fibroblasts of patients with rheumatoid arthritis by ultracentrifugation, size exclusion chromatography and modified polymer precipitation.Methods:The exosomes were extracted from human synovial fibroblasts by ultracentrifugation, size exclusion chromatography and modified polymer precipitation. Transmission electron microscopy, particle size detection and western Blot were used to identify the morphological characteristics, particle size distribution, concentration, and expression of marker proteins. One-way analysis of variance (ANOVA) was used for comparison among the three groups, and LSD- t test was used for pairwise comparison. P<0.05 was considered statistically significant. Results:Exosomes could be successfully obtained with all three extraction methods. The typical "saucer-like" structure could be observed under transmission electron microscope. The marker proteins of exosomes TSG101, Syntenin-1 and CD63 were all detectable by western blot. The peaks of main particle size were located within 30~150 nm. As for purity, the exosomes obtained by ultracentrifugation showed the highest purity, while modified polymer precipitation was the worst, with a large number of polymer particles and impurities protein. The purity of exosomes obtained by size exclusion chromatography was the moderate. For extraction efficiency, concentrations of exosomes particles obtained by the three methods were different ( F=9.61, P=0.049), and modified polymer precipitation was significantly higher than ultracentrifugation in terms of concentration of exosomes particles [(98.0±17.0)×10 10 particles/ml vs (11.6±7.7)×10 10 particles/ml, t=-4.34, P=0.023]. Conclusion:Human synovial fibroblasts derived exosomes canbe obtained by three methods. Ultracentrifugation is time-consuming, but can produce high-purity exosomes, which may be considered in the situation when high purity requirement with large volume samples are needed. Size exclusion chromatography is a good choice with high yield and purity exosomes, and suitable for small volume samples. Modified polymer precipitation is not recommended due to production of lowest purity exosomes.

Objective:To evaluate the clinical value of the adjusted global antiphospholipid syndrome score (aGAPSS) in patients with persistent antiphospholipid antibodies (aPL).Methods:The clinical data of patients who were continuously positive for aPL from May 2012 to August 2022 were retrospectively analyzed, except for patients complicated with connective tissue diseases. Demographic data, traditional cardiovascular thrombosis risk factors, aPL profile, and clinical manifestations included and not included in antiphospholipid syndrome (APS) were collected, and aGAPSS was calculated for all patients according to risk indicators and the correlation with clinical manifestation was analyzed through rank sum test. The diagnostic value of aGAPSS for different clinical manifestations was evaluated by the receiver operator characteristic (ROC) curve.Results:A total of 67 patients with persistent aPL were enrolled, including 15 patients with persistent extra-criteria positive aPL but did not meet the APS classification criteria and 52 patients with a clear diagnosis of primary APS, of which 20 had a history of thrombosis, 36 had a history of pregnancy morbidity, and 24 had extra-criteria clinical manifestations. Patients with history of any thrombosis or arterial thrombosis scored significantly higher than those with no history of thrombosis [any history of thrombosis 11.50 (8.25, 13.00) vs 8.00 (4.00, 13.00), Z=2.33, P=0.020; arterial thrombosis history 11.00 (9.00, 14.00) vs 8.00 (4.00, 13.00), H=6.21, P=0.043]. The aGAPSS score of patients with extra-criteria clinical manifestations was significantly higher than that of patients without corresponding clinical manifestations [13.00 (8.25, 13.00) vs 8.00 (4.00, 11.00), Z=2.81, P=0.005], and the aGAPSS score of patients with thrombocytopenia was significantly higher than that of patients without thrombocytopenia [12.50 (8.00, 13.25) vs 8.00 (4.00, 13.00), Z=2.23, P=0.026]. A subgroup analysis of pregnant women found no statistically significant difference in aGAPSS scores between groups with or without a history of pregnancy morbidity. With thrombosis as the endpoint event, aGAPSS had the highest diagnostic value at 10 points(sensitivity and specificity were 65.00% and 77.78%, respectively). Conclusion:In patients with postivity aPL positivity, aGAPSS score is correlated with thrombosis history and extra-criteria clinical manifestations, especially thrombocytopenia.

Objective:To evaluate the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) in reflecting the effectiveness of secukinumab (SEC) in psoriatic arthritis (PsA).Methods:Forty-nine patients treated with SEC betwee January 2019 and March 2023 from the PsA cohort (PKUPsA cohort) were enrolled. Demographic data and disease activity indexes, laboratory markers including NLR, PLR, SII, patient-reported outcome measures at baseline, 6 months and 12 months after SEC treatment were retrospectively analyzed. Paired-sample t test and Wilcoxon signed-rank test were used to compare the changes of inflammatory markers before and after the treatment, Spearman correlation analysis was used to explore the correlation between NLR, PLR, SII and other clinical and laboratory indicators, and Cox proportional hazards model was used to analyze the predictive factors of achieving minimal disease activity (MDA) during 12 months of SEC treatment. Results:After 6 months of SEC treatment, PLR and SII decreased significantly from the baseline (142 ±62 vs. 164 ± 61, t=2.55, P= 0.016, n=31; 553 ± 428 vs. 725 ± 361, t= 2.28, P= 0.030, n=31); After 12 months of treatment, SII also showed a statistically significant decline from the baseline (613 ± 407 vs. 792 ± 365, t=2.33, P=0.028, n=26). Patients′ C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity index for psoriatic arthritis (DAPSA) score at the 6th and the 12th month of SEC treatment were significantly lower than baseline as well. In terms of the correlation between NLR, PLR, SII and other indicators, there was a stable positive correlations between the baseline level and the changes over 6-month and 12-month after SEC treatment in NLR, PLR, SII, CRP and ESR ( r=0.29~0.61, P<0.05). Similarly, NLR, SII at baseline and the changes at month 6 and month 12 from baseline showed positive associations consistently with tenderness joint counts ( r=0.34~0.63, P<0.05) and DAPSA score ( r=0.30~0.68, P<0.05). Stable positive correlations of SII with visual analogue scale (VAS) of pain ( r=0.39~0.56, P<0.01) and patient global assessment (PtGA) ( r=0.33~0.62, P<0.05) were also observed. In addition, there was also positive correlation of NLR, PLR and SII with the generalized anxiety disorder scale (GAD-7) and patient health questionnaire-9 (PHQ-9) score at baseline and 12-month after SEC treatment ( r=0.33~0.78, P<0.05; r=0.37~0.58, P<0.05). Cox proportional hazards model showed that baseline PLR and DAPSA score were adverse factors for achieving MDA during 12 months of treatment, however, baseline DAPSA score was the only independent predictor [ HR(95% CI)=0.87 (0.78, 0.97), P=0.010]. Conclusion:NLR, PLR, and SII can be used as biomarkers for monitoring the improvement in disease activity, anxiety and depression levels of patients with PsA, but baseline NLR, PLR, and SII cannot predict the achievement of MDA at 12 months after SEC treatment.

Objective: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with lightchain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. Materials and Methods: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49–63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At followup after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. Results: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%–1.1%] vs. 1.7% [-5.5%–7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%–1.3%] vs. 2.0% [-3.0%–5.0%]; P = 0.01) compared with those with inferior response. Conclusion Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.
Humans ; Arthritis, Rheumatoid ; Cohort Studies ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; East Asian People ; Prospective Studies ; Vaccination/adverse effects*

BACKGROUND: Biological agents, such as tumor necrosis factor inhibitors (TNFi), have been widely used in rheumatoid arthritis (RA) patients and greatly improved goal achievement. The aim of this study was to investigate whether conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) combination was better in reducing relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi plus MTX in RA patients who achieved low disease activity (LDA) with TNFi and MTX therapy. METHODS: RA patients who failed to csDMARDs received an induction therapy of MTX plus TNFi for maximally 12 weeks. Those achieving LDA in 12 weeks were randomly assigned at a 1:1:1 ratio into three groups: (A) adding hydroxychloroquine and sulfasalazine for the first 12 weeks and then discontinuing TNFi for the following 48 weeks; (B) maintaining TNFi and MTX for 60 weeks; and (C) maintaining TNFi and MTX for the first 12 weeks and then discontinuing TNFi for the following 48 weeks. The primary outcome was relapse. RESULTS: A total of 117 patients were enrolled for induction therapy and 67 patients who achieved LDA within 12 weeks were randomized, with 24, 21, and 22 patients in groups A, B, and C, respectively. The relapse rates of groups A and B during the entire 60 weeks were comparable [10/22 (45.5%) vs. 7/20 (35.0%), χ2 = 0.475, P = 0.491], however, significantly lower than that of group C [10/22 (45.5%) vs. 17/20 (85.0%), χ2 = 5.517, P = 0.019; 7/20 (35.0%) vs. 17/20 (85.0%), χ2 = 11.035, P = 0.004, respectively]. Taking RMB 100,000 Yuan as the threshold of willingness to pay, compared to MTX monotherapy (group C), both TNFi maintenance and triple csDMARDs therapies were cost-effective, but triple csDMARDs therapy was better. CONCLUSION: For RA patients who have achieved LDA with TNFi and MTX, csDMARDs triple therapy was a cost-effective option in favor of reducing relapse. TRIAL REGISTRATION ClinicalTrials.gov, NCT02320630.
Humans ; Cost-Benefit Analysis ; Drug Therapy, Combination ; Treatment Outcome ; Arthritis, Rheumatoid/drug therapy* ; Antirheumatic Agents/therapeutic use* ; Methotrexate/therapeutic use* ; Recurrence

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints with high risk of disability. In recent years, remarkable progress has been made towards the diagnosis and treatment of RA, and the international RA guidelines have been also kept updated. Nevertheless, there are many challenges in China, especially inadequate number of rheumatologists and insufficient experience in the diagnosis and treatment of RA. Therefore, Chinese Rheumatology Association drafted the standardized diagnosis and treatment of RA based on the available evidence, so as to improve the management of RA patients in China.

Objective:To improve the ability of identification and differential diagnosis of severe systemic lupus erythematosus (SLE).Methods:A severe SLE patient with lupus myocarditis, neuropsychiatric lupus, thrombotic microangiopathy (TMA) and other multiple system involvement was reported and discussed.Results:A young female patient developed albuminuria 5 months ago, edema of both lower limbs 3 months ago, change of consciousness 1 month ago and two convulsions attack 2 days ago. She experienced life threatening manifestations such as neuropsychiatric lupus, myocardial involvement of lupus, and TMA. During the course, her condition was generally improved after glucocorticoid pulse therapy and plasma exchange.Conclusion:Various complicated clinical manifestations related to SLE need to be recognized earlier and intervened as soon as possible.

Objective:To investigate the clinical characteristics, prognosis, and risk factors for poor prognosis of neuropsychiatric systemic lupus erythematosus (NPSLE) .Methods:Patients who were diagnosed as NPSLE between January 2009 to January 2019 in Peking University First Hospital were included. Patients with neuro-psychiatric symptoms caused by other reasons such as infection and metabolic disorders were excluded. Patients were retrospectively followed up by telephone or medical records. Continuous variables were compared by student t test or Wilcoxon rank sum test. Quantitative variables were compared by chi-square test. Survival was analyzed by Kaplan-Meier curve. Predictive factors of prognosis was estimated by using Cox regression analysis. Results:One hundred and nine NPSLE patients were included. Thirteen (11.9%) were male and 96 (88.1%) were female with a median age of 33 years old. Central nervous system involvement was predominant (89/109, 81.7%) . The most common types were headache, cerebrovascular disease and epilepsy. Cranial neuropathy was the most common type at the initial onset of systemic lupus erythematosus (SLE) , while cerebrovascular disease was more common when SLE relapsed. Patients who demonstrated NPSLE at the initiation of SLE had shorter survival time than those who got NPSLE when SLE relapsed [ (32±26) months vs (197±79) months, t=2.834, P=0.037]. Among the 105 patients with complete followed up data, the follow up time was 118.0 (1.4, 525.7) months and 53.1 (0.4, 363.0) months from the onset of SLE and NPSLE, respectively. The mortality rate was 14.3% (15/105) . The survival rates of 1-5 years were 96.2%, 94.3%, 91.0%, 89.9% and 88.3%, respectively. The survival time was (180±138) months and (33±32) months, t=3.861 , P<0.01) from the onset of SLE and NPSLE, respectively. The major causes of death were infection, NSPLE and cardiovascular disease. Cerebrovascular disease was the independent risk factor for death [ RR=3.413, 95% CI (1.049, 11.102) , P=0.041]. Conclusion:Cranial neuropathy is the most common type at the initial onset of SLE, while cerebrovascular disease is more common when SLE relapsed. Patients who had NPSLE at the initiation of SLE have shorter survival time than those who got NPSLE when SLE relapsed. Cerebrovascular disease is the independent risk factor of death of NPSLE patients.

Primary biliary cholangitis is a chronic autoimmune cholestatic disease with a progressive course. This disease is not rare in China, but standardized diagnosis and treatment for primary biliary cholangitis are insufficient. Based on the evidence and guidelines from China and other countries, Rheumatology Branch of Chinese Medical Association developed the recommendations of diagnosis and treatment for primary biliary cholangitis in China. The aim is to help clinicians recognize clinical characters, therapeutic selection and prognosis judgement of primary biliary cholangitis, which will contribute to make diagnosis in time, to select treatment properly and to manage follow-up scientifically.