Validation of new classification criteria of rheumatoid arthritis in an international multicentre study.

OBJECTIVES: Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study. METHODS: A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India. The clinical and laboratory parameters were recorded. We compared the sensitivity, specificity, predictive value, likelihood ratio (LR), and the area under the ROC curve (AUC) of three criteria in these cohorts. Concordance between the three criteria was calculated with the Kappa coefficient. RESULTS: Three hundred and twelve RA and 294 non-RA patients were included. The Early Rheumatoid Arthritis (ERA) criteria had significantly higher specificity compared to the 2010 ACR/ EULAR criteria (83.7% vs. 78.2%, p=0.02) and sensitivity were similar (79.2% vs. 78.5%, p=0.883). In comparison with the 1987 ACR criteria, the ERA criteria had higher sensitivity (79.2% vs. 54.5%, p<0.001) but lower specificity (83.7% vs. 89.1%, p<0.001), and the AUC of the ERA criteria (0.878) was comparable to the 2010 ACR/EULAR criteria (0.849) and higher than the 1987 ACR criteria (0.791, p<0.0001). Patients from the three countries, seronegative and very early arthritis cohorts yielded consistent results. CONCLUSIONS: The ERA criteria demonstrate a better performance across ethnics in early RA diagnosis, and is more feasible in daily practice.

Correlation of Polymorphisms of Natural Resistance-Associated Macrophage Protein 1 (NRAMP1) Gene and Smoking with the Risk of Rheumatoid Arthritis in Chinese Han People.

BACKGROUND In this study we report on the possible connection between single nucleotide polymorphisms (SNPs) in natural resistance-associated macrophage protein 1 (NRAMP1) gene and the risk of rheumatoid arthritis (RA) in the Chinese Han population. MATERIAL AND METHODS A total of 248 participants consisting of 116 RA cases and 132 healthy individuals were recruited for the current study. Genotyping for NRAMP1 gene polymorphisms was implemented using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The chi-square test was used to detect discrepancies in genotype and allele frequencies between the RA case group and the control group. Odds ratios (ORs) with 95% confidence intervals (CIs) was used to evaluate relative risk of RA. The results were adjusted by logistic regression analysis. RESULTS The TT genotype and T allele in rs17221959 showed dramatically different distribution between RA cases and healthy controls. After adjustment, TT genotype (OR=0.338, 95%CI=0.278-1.214, P=0.028) and T allele (OR=0.608, 95%CI=0.298-0.956, P=0.005) showed close association with reduced risk of RA. For rs1059823, no obvious diversity was uncovered in either genotype or allele distribution between the 2 groups. Interaction analysis showed that smoking decreased the protective function of TT in rs17221959. CONCLUSIONS This study suggested that the TT genotype and T allele in rs17221959 decreased RA risk. Smoking could decrease the protective effect of TT.

TLR4+CXCR4+ plasma cells drive nephritis development in systemic lupus erythematosus.

OBJECTIVES: In patients with systemic lupus erythematosus (SLE), immune tolerance breakdown leads to autoantibody production and immune-complex glomerulonephritis. This study aimed to identify pathogenic plasma cells (PC) in the development of lupus nephritis. METHODS: PC subsets in peripheral blood and renal tissue of patients with SLE and lupus mice were examined by flow cytometry and confocal microscopy, respectively. Sorting-purified PCs from lupus mice were adoptively transferred into Rag2-deficient recipients, in which immune-complex deposition and renal pathology were investigated. In culture, PCs from lupus mice and patients with SLE were treated with a TLR4 inhibitor and examined for autoantibody secretion by enzyme-linked immunospot assay (ELISPOT). Moreover, lupus mice were treated with a TLR4 inhibitor, followed by the assessment of serum autoantibody levels and glomerulonephritis activity. RESULTS: The frequencies of TLR4+CXCR4+ PCs in peripheral blood and renal tissue were found significantly increased with the potent production of anti-dsDNA IgG, which were associated with severe renal damages in patients with SLE and mice with experimental lupus. Adoptive transfer of TLR4+CXCR4+ PCs from lupus mice led to autoantibody production and glomerulonephritis development in Rag2-deficient recipients. In culture, TLR4+CXCR4+ PCs from both lupus mice and patients with SLE showed markedly reduced anti-dsDNA IgG secretion on TLR4 blockade. Moreover, in vivo treatment with TLR4 inhibitor significantly attenuated autoantibody production and renal damages in lupus mice. CONCLUSIONS: These findings demonstrate a pathogenic role of TLR4+CXCR4+ PCs in the development of lupus nephritis and may provide new therapeutic strategies for the treatment of SLE.

Chinese registry of rheumatoid arthritis (CREDIT): I. Introduction and prevalence of remission in Chinese patients with rheumatoid arthritis.

OBJECTIVES: To introduce the Chinese Registry of rhEumatoiD arthrITis (CREDIT), which is the first nationwide, multicentre, online rheumatoid arthritis (RA) registry in China, and to depict major cross-sectional data and treatment strategies of Chinese RA patients. METHODS: RA patients who fulfilled the 2010 ACR/EULAR classification criteria for rheumatoid arthritis were recruited into the registry by their rheumatologists from 144 clinical centres in China. Data, including demographics, disease characteristics, co-morbidities, treatment, and adverse reactions, were collected and documented through the predefined protocol. RESULTS: 8071 registered patients (F:M = 4.03:1) were registered up to May 2017. Mean age at symptom onset and at diagnosis was 46.15±14.72y and 48.68±14.54y, respectively. Point prevalence of remission (95% CIs) was 14.88% (14.10-15.66%), 4.23% (3.79-4.66%), 4.25% (3.81-4.69%), and 4.27% (3.83-4.72%) according to DAS28-CRP, CDAI, SDAI, and the 2011 ACR/EULAR remission criteria, respectively. 38.84% and 38.11% of treatment-naïve patients (n=3262) were in moderate (3.25.1) disease activity, respectively. Among treatment-naïve patients, those who were initiated on treatment with bDMARDs had higher disease activity than those who were treated with csDMARDs (p<0.05). Three months after initiating bDMARDs, 19.29% (n=38) of patients achieved remission (DAS28-CRP<2.6). CONCLUSIONS: The CREDIT registry is an effective tool for real-world study of RA patients in China. By providing information for diagnosis and treatment regimen, the CREDIT registry can enhance the application of treat-to-target (T2T) strategy and improve patient outcomes in China.

Correlation of Axial Spondyloarthritis with Anxiety and Depression.

BACKGROUND This study compared anxiety and depression in patients with nonradiographic axial spondyloarthritis (nr-axSpA) versus patients with ankylosing spondylitis (AS), and examined the relationship between clinical characteristics and psychological status. MATERIAL AND METHODS Patients diagnosed with axial spondyloarthritis (axSpA) were recruited for the study. Disease status was evaluated by the bath ankylosing spondylitis disease activity index (BASDAI), the bath ankylosing spondylitis functional index, visual analog scale, and the level of inflammatory markers. Psychological status was evaluated by the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS). RESULTS Sixty patients with axSpA were enrolled in the study, including 40 patients with AS and 20 patients with nr-axSpA. Patients with AS and patients with nr-axSpA had similar disease status and psychological status. Anxiety was significantly associated with disease status and SDS score (P<0.05 for all), whereas BASDAI (odds ratio [OR]=0.28, 95% CI=0.08-0.97, P=0.045) and SDS (OR=0.90, 95% CI=0.82-0.98, P=0.014) protected against anxiety. Depression was obviously correlated with smoking history, disease status, and SAS score (P<0.05 for all). Smoking history (OR=10.18, 95% CI=1.23-84.23, P=0.031) and SAS score (OR=0.85, 95% CI=0.75-0.97, P=0.014) were negatively correlated with risk of depression. CONCLUSIONS Patients with AS and patients with nr-axSpA had similar psychological status in terms of anxiety and depression. Disease status and smoking were significantly correlated with psychological status. Patients with higher SAS scores were more likely to have depression. The results of this study may be helpful to clinically guide psychological interventions for patients with axSpA.

Roles of B Cell-Intrinsic TLR Signals in Systemic Lupus Erythematosus.

Toll-like receptors (TLRs) are a large family of pattern recognition receptors. TLR signals are involved in the pathogenesis of systemic lupus erythematosus. Mouse and human B cells constitutively express most TLRs. Many B cell subpopulations are highly responsive to certain TLR ligation, including B-1 B cells, transitional B cells, marginal zone B cells, germinal center B cell and memory B cells. The B cell-intrinsic TLR signals play critical roles during lupus process. In this review, roles of B cell-intrinsic TLR2, 4, 7, 8 and 9 signals are discussed during lupus pathogenesis in both mouse model and patients. Moreover, mechanisms underlying TLR ligation-triggered B cell activation and signaling pathways are highlighted.

Classification criteria of early rheumatoid arthritis and validation of its performance in a multi-centre cohort.

OBJECTIVES: To develop classification criteria for early rheumatoid arthritis (ERA) based on a large cohort of early inflammatory arthritis patients and to evaluate the performance of these criteria. METHODS: The study population comprised a cohort of early inflammatory arthritis patients with symptom duration less than one year. Classification criteria of ERA were developed by incorporating the most sensitive or specific variables. Performance of the ERA criteria, 1987 ACR and 2010 ACR/EULAR criteria were evaluated. RESULTS: A total of 803 patients were enrolled in this study. By the end of the one year follow-up, 514 patients were diagnosed with RA, 251 with other rheumatic diseases, and 38 patients with undifferentiated arthritis. The ERA criteria are as follows: 1) morning stiffness ≥30 minutes; 2) arthritis of 3 or more joint areas; 3) arthritis of hand joints; 4) positive RF; 5) positive anti-CCP antibody. Rheumatoid arthritis is defined by the presence of 3 or more of the criteria. The sensitivity (84.4%) of the ERA classification criteria was much higher than the 1987 ACR criteria (58.0%). In a validation cohort of early inflammatory arthritis patients, the area under the ROC curves (AUC) showed a better performance for the ERA criteria (0.906, 95%CI 0.866 to 0.945) than the 1987 ACR criteria (0.786, 95%CI 0.725 to 0.848) and the 2010 ACR/EULAR criteria (0.745, 95%CI 0.677 to 0.814). CONCLUSIONS: A set of ERA classification criteria has been developed with good performance for early RA. It is applicable in clinical practice and research.

NLRP1 gene polymorphism influences gene transcription and is a risk factor for rheumatoid arthritis in han chinese.

OBJECTIVE: The inflammasome-related protein NLRP1/NALP1 has been implicated in the onset and progression of some autoimmune diseases. This study was undertaken to determine whether a polymorphism in the NLRP1 gene is associated with susceptibility to rheumatoid arthritis (RA) in Han Chinese and to assess the functional implications of this association. METHODS: RA patients (n = 190) and matched healthy controls (n = 190) residing in the city of Chengdu were genotyped for the NLRP1 promoter polymorphisms rs6502867 and rs878329. Genotyping for rs878329 was performed in a second set of subjects (n = 1,514) residing in the city of Chongqing. The effect of each polymorphism on NLRP1 transcription was evaluated by dual-luciferase assay, while the effect on DNA protein interaction was determined by electrophoretic mobility shift assay. Differential expression of NLRP1 in individuals with different genotypes was investigated by real-time quantitative polymerase chain reaction. RESULTS: The polymorphism rs878329, but not rs6502867, was associated with RA (odds ratio [OR] 0.83, P = 0.02 for the C allele; OR 0.42, P = 0.01 for the CC genotype). The GG genotype of rs878329 was the risk genotype for RA (OR 2.38) and had a runt-related transcription factor 1 binding site that up-regulated NLRP1 transcription. Individuals with the RA risk genotype GG had significantly higher NLRP1 messenger RNA levels than those with the CC genotype among the Han Chinese population. CONCLUSION: Our findings indicate that NLRP1 is associated with RA in Han Chinese. The G allele of rs878329 in the NLRP1 promoter up-regulates gene transcription and confers the risk of RA.

Analysis of fecal Lactobacillus community structure in patients with early rheumatoid arthritis.

The objective of this study was to analyze human fecal Lactobacillus community and its relationship with rheumatoid arthritis. Samples taken from rheumatoid arthritis (RA) patients and healthy individuals were analyzed by quantitative real-time PCR. Bacterial DNA was extracted from feces, and amplicons of the Lactobacillus-specific regions of 16S rRNA were analyzed by denaturing gradient gel electrophoresis. The richness, Shannon-Wiener index, and evenness of gut microbiota of both groups were analyzed to compare fecal Lactobacillus community structures. Results of this study demonstrated that fecal microbiota of RA patients contained significantly more Lactobacillus (10.62 ± 1.72 copies/g) than the control group (8.93 ± 1.60 copies/g). Significant increases were observed in RA patients in terms of the richness, Shannon-Wiener, and evenness measures, indicating more bacterial species, and increased bacterial diversity and abundance. These results suggest a potential relationship between Lactobacillus communities and the development and progression of rheumatoid arthritis.

[Single nuclear polymorphisms in exon 3 of POMC gene and the association with growth traits in Hu sheep and East Friesian x Hu crossbred sheep].

Pro-opiomelancortin (POMC) plays important roles in the regulation of food intake and energy expenditure. The sheep exon 3 of gene POMC was amplified and sequenced by screening the DNA pools to select single nuclear polymorphisms and analyze the association with the growth traits. Two silent SNP mutations (g.273 T/C and g.456 G/A) in Hu sheep were identified. PCR-restriction fragment length polymorphism (RFLP) was used to test the g.273 T/C and the association between the g.273 T/C polymorphism and some growth traits was analyzed in Hu sheep (n = 162) and East Friesian x Hu crossbred sheep (n=130). The results showed that three genotypes, TT, TC and CC, were detected in Hu sheep with the frequencies of 0.469, 0.438 and 0.093, respectively. Two genotypes, TT and TC, were detected in East Friesian x Hu crossbred sheep with the frequencies of 0.754 and 0.246, respectively. The association analysis showed that in Hu sheep the two-month weaning weight, four-month rump height of genotype CC and the four-month body length, cannon circumference of genotype TC were significantly higher than those of genotype TT (P < 0.05); the four- and six-month weight of genotype CC were significantly higher than those of genotypes TT and TC (P < 0.01); the four-month body height and body length of genotype CC were significantly higher than those of genotypes TT (P < 0.01) and TC (P < 0.05); the four-month cannon circumference of CC genotype was significantly higher than that of TT genotype (P < 0.01). In East Friesian x Hu crossbred sheep the two-month weaning weight, four-month weight, body height, body length, chest depth and cannon circumference of genotype TC were significantly higher than those of genotype TT (P < 0.05); the six-month weight of genotype TC was significantly higher than that of genotype CC (P < 0.01). In conclusion, the exon 3 of gene POMC was associated with growth traits, and C allele was beneficial to the increase of body weight and body size traits of sheep, which potentially afford a good foundation for further study on POMC gene as aided breeding markers for growth traits in sheep.

Which method delivers greater signal-to-noise ratio: Structural equation modelling or regression analysis with weighted composites?

Observational data typically contain measurement errors. Covariance-based structural equation modelling (CB-SEM) is capable of modelling measurement errors and yields consistent parameter estimates. In contrast, methods of regression analysis using weighted composites as well as a partial least squares approach to SEM facilitate the prediction and diagnosis of individuals/participants. But regression analysis with weighted composites has been known to yield attenuated regression coefficients when predictors contain errors. Contrary to the common belief that CB-SEM is the preferred method for the analysis of observational data, this article shows that regression analysis via weighted composites yields parameter estimates with much smaller standard errors, and thus corresponds to greater values of the signal-to-noise ratio (SNR). In particular, the SNR for the regression coefficient via the least squares (LS) method with equally weighted composites is mathematically greater than that by CB-SEM if the items for each factor are parallel, even when the SEM model is correctly specified and estimated by an efficient method. Analytical, numerical and empirical results also show that LS regression using weighted composites performs as well as or better than the normal maximum likelihood method for CB-SEM under many conditions even when the population distribution is multivariate normal. Results also show that the LS regression coefficients become more efficient when considering the sampling errors in the weights of composites than those that are conditional on weights.

Efficacy and Safety of CMAB008 Compared with Innovator Infliximab in Patients with Moderate-to-Severe Rheumatoid Arthritis Receiving Concomitant Methotrexate: A Randomized, Double-blind, Multi-center, Phase III Non-inferiority Study.

OBJECTIVES: The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. METHODS: We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than - 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. RESULTS: In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were - 4.6% and the lower limit of one-sided 97.5% confidence interval was - 14.29%, not less than the lower limit of the non-inferiority margin (- 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference - 4.6%, 95% CI - 14.29% to 5.12%) and PPS (difference - 3.3%, 95% CI - 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. CONCLUSIONS: Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. TRIAL REGISTRATION NUMBER: NCT03478111.

Inhibitory Effect of Curcumol on Jak2-STAT Signal Pathway Molecules of Fibroblast-Like Synoviocytes in Patients with Rheumatoid Arthritis.

Hyperplasia of synovial membrane in rheumatoid arthritis (RA) is a critical pathological foundation for inducing articular injury. The janus kinase and signal transducer and activator of transcription (Jak-STAT) pathway plays a critical role in synovial membrane proliferation induced by platelet-derived growth factor (PDGF). To explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant zedoary rhizome, the changes of Jak2-STAT1/3 signal pathway-related molecules in synoviocytes were observed in vitro. In this study, the fibroblast-like synoviocytes (FLS) in patients with RA were collected and cultured. The following parameters were measured: cell proliferation (WST-1 assay), cell cycles (fluorescence-activated cell sorting, FACS), STAT1 and STAT3 activities (electrophoretic mobility shift assay, EMSA), and the protein expressions of phosphorylated Jak2, STAT1, and STAT3 (Western blot). It was shown that curcumol could inhibit the RA-FLS proliferation and DNA synthesis induced by PDGF-BB in a dose-dependent manner in vitro. The transcription factors activities of STAT1 and STAT3 were obviously elevated after PDGF-BB stimulation (P < 0.05). Super-shift experiments identified the STAT1 or STAT3 proteins in the complex. Furthermore, the different concentration curcumol could downregulate the DNA binding activities of STAT1 and STAT3 (P < 0.05) and inhibit the phosphorylation of Jak2 while it had no effect on the protein expressions of STAT1 and STAT3. Positive correlations were found between changes of cell proliferation and DNA-binding activities of STAT1 and STAT3, respectively (P < 0.01). In conclusion, curcumol might suppress the FLS proliferation and DNA synthesis induced by PDGF-BB through attenuating Jak2 phosphorylation, downregulating STAT1 and STAT3 DNA-binding activities, which could provide theoretical foundation for clinical treatment of RA.

Sirolimus versus tacrolimus for systemic lupus erythematosus treatment: results from a real-world CSTAR cohort study.

OBJECTIVE: The effectiveness and safety of sirolimus for SLE treatment have been shown in some uncontrolled studies. However, a comparison of sirolimus with other classic immunosuppressants has not been reported. We conducted the study to compare the effectiveness and safety of sirolimus versus tacrolimus for SLE treatment. METHODS: A real-world cohort study was conducted. Patients with clinically active SLE who were prescribed sirolimus or tacrolimus were enrolled. Propensity score matching was used to ensure equivalent disease conditions and background medications. SLE disease activity indices, serological parameters, steroid doses, modification of other immunosuppressants, renal effectiveness and adverse events were compared between the two groups at 3-month, 6-month, 9-month and 12-month follow-up visits. RESULTS: Data from 52 patients in each of the sirolimus and tacrolimus groups were analysed. Indices regarding the effectiveness of sirolimus, including Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, physician's global assessment (PhGA) scores, and proportion of patients with SLEDAI-2K reduction of ≥4 and PhGA increase of <0.3, were equivalent to those of tacrolimus at all follow-up timepoints (all p≥0.05). Greater improvements in complement levels were observed in the sirolimus group at 3 and 6 months. Higher percentages of patients with prednisone doses ≤7.5 mg/day were observed in the sirolimus group at all timepoints. Seventeen adverse events in the sirolimus group were recorded. None was severe or led to drug discontinuation. CONCLUSIONS: Overall, sirolimus was as effective as tacrolimus in the treatment of SLE. Sirolimus had better effects on serological improvement and glucocorticoid tapering. Sirolimus was well tolerated in patients with SLE.

Chinese registry of rheumatoid arthritis (CREDIT) V: sex impacts rheumatoid arthritis in Chinese patients.

BACKGROUND: The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients. METHODS: Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits. RESULTS: A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0 vs . 6.7 mg/L), pain visual analogue scale (4.8 vs . 4.5), patient's and physician's global assessment (4.9 vs . 4.5 and 4.9 vs . 4.5), 28-joint disease activity score using DAS28-CRP (4.3 vs . 4.0) simplified disease activity index (21.9 vs . 19.9), and clinical disease activity index (19.3 vs . 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4% vs . 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women. CONCLUSIONS: In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.

The Impact of Traditional Chinese Medicine QingreHuoxue Treatment and the Combination of Methotrexate and Hydroxychloroquine on the Radiological Progression of Active Rheumatoid Arthritis: A 52-Week Follow-Up of a Randomized Controlled Clinical Study.

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). QingreHuoxue treatment (QingreHuoxue decoction [QRHXD]/QingreHuoxue external preparation [QRHXEP]) is a Chinese medicine treatment for RA. To date, very few studies have compared the long-term effects of QRHXD with those of conventional disease-modifying antirheumatic drugs on RA disease activity and radiological progression. QRHXD delayed the radiological progression and showed long-term clinical efficacy of RA. In clinical experiments, the clinical evidence of delaying the radiological progression of RA patients was obtained. A portion of the patients who participated in the "Traditional Chinese Medicine QingreHuoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis" study were followed up for 52 weeks, and intention-to-treat (ITT) and compliance protocol (PP) analyses were used to collect and compare the clinical indicators and imaging data between baseline and week 52. Two radiologists who were blind to treatment scored the images independently. Of the 468 subjects, 141 completed the 52-week follow-up. There were no significant differences among the three groups: the traditional Chinese medicine comprehensive treatment group, the Western medicine treatment group, and the integrated traditional Chinese and Western medicine treatment group. There were no differences in the total Sharp score, joint space stenosis score, and joint erosion score at baseline or 52 weeks. In the comparison of the estimated annual radiographic progression (EARP) and the actual annual Sharp total score changes among the three groups, the actual changes were much lower than the EARP at baseline. The radiological progress in all three groups was well controlled. Results of the ITT and PP data sets showed that the disease activity score 28 level of the three groups at 52 weeks was significantly lower than that at baseline. During the 52-week treatment period, the clearance of heat and promotion of blood circulation controlled disease activity and delayed the radiological progress of active RA.

China rheumatoid arthritis registry of patients with Chinese medicine (CERTAIN): Rationale, design, and baseline characteristics of the first 11,764 enrollees.

BACKGROUND: Chinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PURPOSE: The main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. STUDY DESIGN: The CERTAIN is a prospective, multicenter, observational disease registry. METHODS: Adult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. RESULTS: In the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. CONCLUSIONS: The CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05219214).

Localization of cerebral functional deficits in patients with non-neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NP-SLE) is a common complication of systemic lupus erythematosus (SLE), and clinical interventions are of only limited efficacy despite relatively high prevalence. Such complications have been studied extensively, but the pathoetiology of NP-SLE has not yet been elucidated. Diagnosis of NP-SLE focuses primarily on psychological manifestations, and the underlying mechanisms leading to neuropsychiatric complications remain unknown. To address potential changes in brain function before NP-SLE development, we used resting-state functional magnetic resonance imaging (MRI) to compare regional brain activity in SLE patients versus matched controls. We report that regional activity in cerebellum and in areas of the default mode network are attenuated in patients with SLE, and moreover individual alterations in cerebellar activity correlated positively with the disease activity index. These findings provide direct evidence that significant alteration of brain function, resembling that observed in patients with NP-SLE, is already present in SLE patients without neuropsychiatric complications, highlighting the need for early evaluation and intervention in SLE patients. Furthermore, the disease activity rating correlated with regional functional alterations in the cerebellum, suggesting that the cerebellum could play a role in the pathogenesis of NP-SLE.

[Effect of methotrexate in treating patients with rheumatoid arthritis of different Chinese medical syndrome patterns].

OBJECTIVE: To study whether the effects of methotrexate were different in treating patients with rheumatoid arthritis (RA) of different Chinese medical syndrome patterns. METHODS: Retrospective analysis was conducted in 312 RA patients treated with methotrexate, the Chinese medical syndrome patterns in them were differentiated into the cold-dampness blocking collateral type (SA), the heat-dampness blocking collateral type (SB), the phlegm blood-stasis intermingling type (SC), and the heat-cold complex type (SD). Parameters including numbers of joint with tenderness (Njt) and that with arthroncus (Nja); patient's morning stiffness duration (MSD), scores estimated by visual analog scale (VAS) and health assessment questionnaire (HAQ); as well as laboratory indices involving rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), etc. were recorded before and after treatment and statistically analyzed. RESULTS: After treatment, improvements were shown in all patients in terms of Njt, Nja, MSD, VAS scores and ESR, showing significant difference as compared with those before treatment (P < 0.05); and the improvements among patients with different Chinese medical syndrome types were different in degree, the best curative effect was shown in patients of SB type (chi2 = 45.3, P < 0.05). CONCLUSIONS: Referring to Chinese medical syndrome patterns, the curative effect of methotrexate on patients with Heat-Dampness blocking collateral pattern is better than on those of other pattern.