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Abstract Background Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24–48). Methods In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated. Results Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported. Conclusion In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups. Trial registration NCT03830203 and EudraCT 2018-002202-31.

Abstract Background The aim of this prospective observational cohort study was to unveil the predictors of treatment response to tocilizumab (TCZ) therapy in rheumatoid arthritis (RA) patients, in terms of clinical characteristics and serum proinflammatory cytokines, especially to explore the predictive value of granulocyte macrophage-colony stimulating factor (GM-CSF). Methods Active adult RA patients with inadequate response to MTX intending to receive TCZ therapy were recruited prospectively in the study. A total of 174 severe RA patients were included for the identification of the associations between treatment response and the following characteristic features: demographics, medications, disease activity, serum proinflammatory cytokines and so on. Results Disease duration (OR = 0.996), tender joint count (TJC)/68 (OR = 0.943), neutrophil ratio (W4/baseline) (OR = 0.224), the high level of GM-CSF > 5 ng/ml (OR = 0.414) at baseline were the independent adverse predictors of good response assessed by clinical disease activity index (CDAI) at week 24 (W24) for TCZ therapy in RA patients. Moreover, DAS28-ESR (OR = 2.951, P = 0.002) and the high level of GM-CSF > 10 ng/ml at baseline (OR = 5.419, P = 0.002) were independent predictors of poor response, but not the high level of GM-CSF > 5 ng/ml (OR = 2.713, P = 0.054). The patients in the high GM-CSF group had significantly higher DAS28-ESR and serum levels of cytokines (IL-17A, IL-1β, IL-6, TNF-α) at baseline, as well as significantly higher rate of non-good response (62.8% vs. 39.4%, P = 0.010) and poor response (27.9% vs. 9.1%, P = 0.004) than the low GM-CSF group at W24. In addition, poor responders had significantly higher levels of GM-CSF with concomitant increase in the serum levels of IL-17A and IL-1β at baseline than those in moderate and good response groups, while serum levels of IL-6 and TNF-α at baseline were not significantly different in three response groups. Conclusion The high levels of GM-CSF (> 5 ng/ml and > 10 ng/ml) at baseline were the independent predictors of non-good response and poor response to TCZ at W24 respectively. The high level of GM-CSF at baseline is a marker of high disease activity and a predictor of poor response to TCZ in severe RA patients, which may facilitate the development of individualized treatment strategies for refractory RA.

Background: Pirfenidone (PFD) is commonly applied for antifibrotic treatment in patients with idiopathic pulmonary fibrosis but has rarely been studied in cases with connective tissue disease-associated interstitial lung diseases (CTD-ILDs). Objectives: We aimed to examine the efficacy of PFD in patients with CTD-ILD based on real-world data. Design: A retrospective cohort study. Methods: This study assessed the clinical features of CTD-ILD patients with or without a 6-month PFD treatment. A linear mixed effects model was employed to evaluate the effectiveness of PFD in alleviating lung function changes. Differences in response to PFD were analyzed based on CTD subtype, imaging classification, and pattern of pulmonary function at baseline. Results: A total of 289 patients with CTD-ILD were included, with 155 (53.6%) receiving PFD treatment and the remaining constituting the control group. Patients with the usual interstitial pneumonia (UIP) pattern were more likely to receive PFD treatment, and a relatively lower proportion of cases in the PFD group received immunosuppressive therapies compared to the control group ( p

ObjectiveTo develop a guideline for selecting biomarkers in the diagnosis and assessment in patients with axial spondyloarthritis (axSpA).MethodA joint effort was carried out by the core team, the literature review team and the multidisciplinary voting panel to formulate recommendations regarding biomarkers in axSpA, using an evidence-based and consensus-based strategy. Certainty of evidence and strength of recommendation were determined, and levels of agreement within the voting panel were calculated.ResultsA total of 20 recommendations were formulated in this guideline, with levels of agreement ranging from 6.48 to 9.71. The two strong recommendations, HLA-B27 testing in patients suspected of axSpA and regular-interval monitoring of CRP/ESR represent the status quo of axSpA evaluation, while the 13 conditional recommendations represent the promising biomarkers with clinical utility in diagnosis, disease activity assessment, prediction of radiographic progression and therapeutic responses. This guideline does not dictate clinical choices of tests on axSpA, and decisions should be made based on comprehensive consideration of costs, accessibility, patients’ values and willingness as well as the objective of testing in the local context.ConclusionThis guideline addresses the interpretation of the clinical significance of biomarkers in axSpA, and the biomarkers endorsed in this guideline composed a clinical toolkit for healthcare professionals to choose from.

Long-term dynamics of biogenic volatile organic compounds (BVOCs) in trees are rarely reported, despite environmental factors (such as climate change) influencing their growth and the subsequent chemical accumulation. For this, tree growth rings provide a promising biological proxy for the long-time variation and correlation with environmental changes. Therefore, tree rings from Pinus tabuliformis (two stem disks and 40 tree cores) were collected in the Taihang Mountain Macaque National Nature Reserve of China. These samples were divided into seven 5-year resolutions over the 34-year period 1985 to 2018. This enabled analysis of multi-decadal variations of compounds and their correlation with climate variability. A total of 292 BVOCs were detected; however, only 18 compounds were found together across all the 7 growth-periods. Temporal analyses showed decreasing trends for monoterpenes (0.026%/yr) and diterpenes (0.120%/yr), whereas alcohols and oxygenated monoterpenes showed increasing trends at 0.031%/yr and 0.042%/yr, respectively. Correlation analyses showed no obvious link to yearly precipitation, while seasonal temperature had a negative effect on monoterpenes and diterpenes but positive effects on alcohols and oxygenated monoterpenes (all P < 0.05). The present study showed that dendrochronology is a suitable method for re-establishing the biological effects from historical climate variability on key tree species.

ObjectiveThis study aimed to identify plasma biomarkers that are significantly altered in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and are closely associated with AAV disease activity, as well as to explore their role in the pathogenesis of AAV.MethodsCytokines were measured using Human Immune Response Panel 80-Plex in plasma from 59 patients with AAV and 20 healthy controls (HCs). The differentially expressed cytokines between the two groups and the possible signaling pathway involved in the pathogenesis of AAV were analyzed by bioinformatics. Relationship analysis was performed between these cytokines and clinical parameters to identify the biomarkers that can effectively indicate disease activity.ResultsWe identified 65 differentially expressed cytokines between the two groups. Among them, 43 cytokines significantly affected the risk of AAV. Bioinformatic analysis showed that the 43 cytokines were primarily enriched in signaling pathways such as cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, chemokine signaling pathway, and IL-17 signaling pathway. The levels of 25 cytokines were significantly positively correlated with Birmingham Vasculitis Activity Score (BVAS), and the levels of 2 cytokines were significantly negatively correlated with BVAS. Receiver operating characteristic analysis showed that 9 cytokines can distinguish between disease relapse and remission (PTX3: area under curve (AUC)=0.932, IL34: AUC=0.856, IL2RA: AUC=0.833, CCL23: AUC=0.826, VEGFA: AUC=0.811, TNFSF13: AUC=0.795, Granzyme A: AUC=0.788, CSF3: AUC=0.773 and IL1A: AUC=0.765). The elevated levels of these 9 cytokines suggested a risk of disease relapse. The AUC of CCL11 in disease relapse and remission was 0.811 (p=0.0116). Unlike the other 9 cytokines, a negatively association existed between CCL11 level and the risk of disease relapse.ConclusionA group of cytokines that may be involved in AAV pathogenesis was identified. Increased PTX3, IL34, IL2RA, CCL23, and VEGFA levels correlate with active disease in AAV and may be used as biomarkers to identify the disease relapse of AAV.

Abstract Introduction Anemia and malnutrition are recognized indicators of suboptimal physical condition in chronic inflammatory diseases. This study aimed to examine the association between anemia, low body mass index (BMI), and clinical outcomes in axial spondyloarthritis (axSpA). Method This cross-sectional analysis utilized data from the multicenter ChinaSpA cohort. A total of 4146 participants with axSpA were categorized into four groups based on BMI and hemoglobin levels: those with both anemia and low BMI, those with anemia only, those with low BMI only, and those with neither condition. Logistic regression analyses were performed to analyze the association between anemia, low BMI, inflammation status, functional impairment, and disease activity. Results Anemia was present in 13.94%, low BMI in 11.99%, and both conditions in 2.15% of axSpA participants. Those with both anemia and low BMI showed significantly higher levels of inflammation (hypersensitive C-reactive protein [hsCRP] 30.60 mg/L vs. 8.44 mg/L), functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI] 3.80 vs. 2.10), and disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] 4.52 ± 2.04 vs. 3.67 ± 2.21; Ankylosing Spondylitis Disease Activity Score calculated with C-reactive protein [ASDAS_CRP] 3.51 ± 1.10 vs. 2.62 ± 1.21) compared to those without these conditions. After adjusting for sex and age, significant associations were observed between elevated hsCRP levels and the presence of low BMI (odds ratio [OR] 1.44, 95% CI 1.17–1.78), anemia (OR 1.91, 95% CI 1.56–2.32), and their concurrent presence (OR 3.59, 95% CI 2.22–5.80). Similarly, increased BASFI was significantly associated with low BMI (OR 1.57, 95% CI 1.25–1.97), anemia (OR 1.47, 95% CI 1.19–1.80), and their combination (OR 3.11, 95% CI 2.02–4.78). Conclusion All-cause anemia and low BMI are prevalent complications in patients with axSpA, exhibiting a significant correlation with elevated inflammation status and functional impairment. The simultaneous occurrence of anemia and low BMI particularly exacerbates clinical outcomes, emphasizing the critical role of comprehensive nutritional assessment and management in the therapeutic strategy for axSpA.

Abstract Objective Dermatomyositis (DM) positive with anti-melanoma differentiation-associated gene 5 (anti-MDA5-DM) is a systemic autoimmune disease with high mortality. This study aimed to explore the risk factors of death in anti-MDA5-DM and validate a prediction model for all-cause mortality in anti-MDA5-DM. Method We conducted a retrospective study using a single-centre cohort of patients with newly onset anti-MDA5-DM from June 1, 2018 to August 31, 2021. Patients were divided into four groups according to baseline ground-glass opacity (GGO) score: Group A, GGO ≤ 1; Group B, 1 3. The primary outcome was death during the follow-up. Secondary outcomes included death within 3, 6, 12 months, severe infection, and remission during the first 12 months. Results A total of 200 patients were included in the study. Based on multivariable Cox regression, the prognostic factors at baseline were identified as CRP > 5 mg/L, serum ferritin (SF) > 600ng/ml, positive anti-Ro52 antibody, prophylactic use of compound sulfamethoxazole (SMZ Co), four-category GGO score: GGO ≤ 1, 1 3. The final mortality of four groups was 16.4, 22.2, 48.5, 92.0%, respectively. Compared with Group A, the Hazards Ratio (HR) of Group B was 1.408, (p = 0.408), HR of Group C was 3.433 (p = 0.005), HR of Group D was 4.376 (p = 0.001). Conclusions GGO score is a reliable predictor for risk stratification in anti-MDA5-DM and may provide guidance for individualized managements of patients.

Abstract 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.

Abstract Background Serum osteocalcin levels are closely related to metabolic syndrome and cardiovascular disease. This study aimed to investigate the relationship between serum osteocalcin levels and cardiometabolic risk factors in patients with type 2 diabetes (T2D) according to age and sex. Methods This cross-sectional study included 1500 patients with T2D (991 men and 509 women) aged ≥ 18 years old. The age- and sex-specific disparities in glycemic and lipid control, as well as cardiometabolic risk factors were evaluated. Results The levels of serum osteocalcin were significantly higher in women aged > 50 years compared with women aged ≤ 50 years (15.6 ± 6.5 ng/mL vs. 11.3 ± 4.5 ng/mL, p 50 years than men aged ≤ 50 years (12.2 ± 4.2 ng/mL vs. 12.9 ± 4.3 ng/mL, p = 0.0081). We performed correlation analyses of serum osteocalcin and cardiometabolic parameters. Serum osteocalcin concentrations were negative associated with FBG and HbA1c levels in women and men ≤ 50 years old, but not in men aged > 50 years old. Serum osteocalcin were negatively correlated with TG and positively correlated with HDL-C and LDL-C only in men aged ≤ 50 years. In binary logistic regression analysis, serum osteocalcin levels were associated with multiple cardiovascular risk factors, as follows: overweight/obese (odds ratio [OR], 0.944; 95% confidence interval [CI], 0.9–0.991, p = 0.02) in men aged > 50 years; high HbA1C and high FBG in women and men aged ≤ 50 years, but not in men aged > 50 years; after adjustment for confounding factors, high TG (OR, 0.905; 95% CI 0.865–0.947, p

Abstract Background Alterations in oral microbiota in patients with systemic lupus erythematosus (SLE) is less evaluated. The aim of this study was to compare the characteristics of the oral microbiome in SLE patients and healthy controls, and construct an SLE classifier based on the oral microbiota. Methods We sequenced tongue-coating samples of individuals in treatment-naïve SLE (n = 182) and matched healthy controls (n = 280). We characterized the oral microbiome and constructed a microbial classifier in the derivation cohort and validated the results in the validation cohorts. Furthermore, the oral microbiome of posttreatment SLE (n = 73) was characterized. Results The oral microbial diversity of SLE was increased, and the microbial community was different between SLE and healthy controls. The genera Prevotella and Veillonella were enriched, while Streptococcus and Porphyromonas were reduced in SLE. In addition, an increase was noted in 27 predicted microbial functions, while a decrease was noted in 34 other functions. Thirty-nine operational taxonomy units (OTUs) were identified to be related with seven clinical indicators. Two OTUs were identified to construct a classifier, which yielded area under the curve values of 0.9166 (95% CI 0.8848–0.9483, p

To solve the problem that the model accuracy remains low when the data are not independent and identically distributed (non-IID) across different clients in federated learning, a privacy-preserving data augmentation scheme was proposed.Firstly, a data augmentation framework for federated learning scenarios was designed.All clients generated synthetic samples locally and shared them with each other, which eased the problem of client drift caused by the difference of clients’ data distributions.Secondly, based on generative adversarial network and differential privacy, a private sample generation algorithm was proposed.It helped clients to generate informative samples while preserving the privacy of clients’ local data.Finally, a differentially private label selection algorithm was proposed to ensure the labels of synthetic samples will not leak information.Simulation results demonstrate that under multiple non-IID data partition strategies, the proposed scheme can consistently improve the model accuracy and make the model converge faster.Compared with the benchmark approaches, the proposed scheme can achieve at least 25% accuracy improvement when each client has only one class of samples.

Abstract Background Lipid and glucose metabolism abnormalities are associated with nonalcoholic fatty liver disease (NAFLD). The triglyceride–glucose (TyG) index is a recently developed indicator that can identify individuals at risk for NAFLD. However, the applicability of the TyG index for identifying NAFLD in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to investigate the ability of the TyG index to identify individuals at risk for NAFLD in the T2DM population. Methods A total of 2280 participants with T2DM were recruited in this cross-sectional study. The TyG index was calculated, and NAFLD was diagnosed by ultrasonography. Binary logistic regression models were used to evaluate the association of the TyG index, glycemic parameters and lipid parameters with NAFLD. Results Logistic regression analysis showed that the TyG index was significantly associated with NAFLD in subjects with T2DM, the odds ratio (OR) were 3.27 (95% confidence interval [CI], 2.03–5.27; P

Abstract. Background:. The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort. Methods:. Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex. Results:. In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P

Abstract Due to dam discharge, waterfalls, sudden increases in water temperature and oxygen production by photosynthesis, the total dissolved gas (TDG) in water is often supersaturated, which may have serious effects on aquatic ecology. When the atmospheric pressure is lower than the TDG pressure in water, the supersaturated dissolved gas in water will slowly release into air. Wall-attached bubbles were formed during the TDG release process. The generation and departure of wall-attached bubbles influence the release process of TDG in water. To simulate the growth period of the wall-attached bubbles under different pressures, a decompression experimental device was designed to record the supersaturated TDG release process. Based on experimental data and mathematical calculations, the quantitative relationship between the bubble growth rate and environmental pressure was obtained. The supersaturated TDG dissipation rate increases monotonically with increasing relative vacuum degree. Applied the calculation method about the wall-attached bubble growth rate, a formula of the supersaturated TDG adsorption flux was proposed, and a prediction method of the TDG release coefficient was established. The simulation results show that with the increasing relative vacuum degree, the TDG release coefficient increases correspondingly, and the adsorption from wall surface area can be obviously promoted. This study provides an important theoretical basis for the accurate calculation of the TDG release process and provides a scientific basis for the accurate prediction of the spatial and temporal distribution of supersaturated TDG under different pressure and solid wall conditions.

ABSTRACT The objectives of this study were to screen for latent tuberculosis infection (LTBI) among patients with systemic lupus erythematosus (SLE) using the T-SPOT.TB assay and to identify factors affecting the assay results. SLE patients were enrolled from 13 tertiary hospitals in eastern, central, and western China from September 2014 to March 2016 and were screened using the T-SPOT.TB assay to detect LTBI. Basic information about the subjects was collected, including gender, age, body mass index (BMI), course of disease, evidence of previous tuberculosis, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, and the use of glucocorticoids and immunosuppressants. Univariate analysis and multivariable logistic regression were performed to identify factors affecting the results of the T-SPOT.TB assay. In all, 2,229 SLE patients were screened using the T-SPOT.TB assay, of whom 334 patients tested positive, yielding a positivity rate of 15% (95% confidence interval [CI], 13.5% to 16.5%). The positivity rate was higher in male than female patients and had an increasing trend with age. Multivariable logistic regression analysis showed that patients over 40 (odds ratio [OR], 1.65; 95% CI, 1.29 to 2.10) and with evidence of previous tuberculosis (OR, 4.43; 95% CI, 2.81 to 6.99) were more likely to have positive T-SPOT.TB results, while patients with a SLEDAI-2K score of ≥10 (OR, 0.61; 95% CI, 0.43 to 0.88), a glucocorticoid dose of ≥60 mg/d (OR, 0.62; 95% CI, 0.39 to 0.98), leflunomide (LEF) treatment (OR, 0.51; 95% CI, 0.29 to 0.88), or tacrolimus (FK506) treatment (OR, 0.40; 95% CI, 0.16 to 1.00) were more likely to have negative T-SPOT.TB results. The frequencies of CFP-10–specific gamma interferon (IFN-γ)-secreting T cells were significantly lower in SLE patients with severe disease activity or high-dose glucocorticoids (P

BackgroundMyositis-specific autoantibodies (MSAs) are clinically used to diagnose and define idiopathic inflammatory myopathy (IIM) subsets. However, the underlying pathogenic mechanisms of patients with different MSAs remain unclear.MethodsA total of 158 Chinese patients with IIM and 167 gender- and age-matched healthy controls (HCs) were enrolled. Transcriptome sequencing (RNA-Seq) was performed with peripheral blood mononuclear cells (PBMCs), followed by the identification of differentially expressed genes (DEGs) and analysis of gene set enrichment analysis, immune cell infiltration, and WGCNA. Monocyte subsets and related cytokines/chemokines were quantified. The expressions of interferon (IFN)-related genes were validated using qRT-PCR and Western blot in both PBMCs and monocytes. We also performed correlation analysis and ROC analysis to explore the potential clinical significance of the IFN-related genes.ResultsThere were 1,364 genes altered in patients with IIM, including 952 upregulated and 412 downregulated genes. The type I interferon (IFN-I) pathway was remarkably activated in patients with IIM. Compared with patients with other MSAs, IFN-I signatures were significantly activated in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. In total, 1,288 hub genes associated with IIM onset were identified using WGCNA, including 29 key DEGs associated with IFN signaling. The patients had more CD14brightCD16- classical, CD14brightCD16+ intermediate, and fewer CD14dimCD16+ non-classical monocyte subsets. Plasma cytokines like IL-6 and TNF and chemokines including CCL3 and MCPs increased. The validation of IFN-I-related gene expressions was consistent with the findings from RNA-Seq. The IFN-related genes were correlated with laboratory parameters and helpful for IIM diagnosis.ConclusionGene expressions were remarkably altered in the PBMCs of IIM patients. Anti-MDA5+ IIM patients had a more pronounced activated IFN signature than others. Monocytes exhibited a proinflammatory feature and contributed to the IFN signature of IIM patients.

Abstract Background Systemic lupus erythematosus (SLE) is a chronic and complex multi-system autoimmune disorder. Higher risks of hematological malignancies (HM) were observed in SLE patients, which was associated with higher mortality. The mechanism and risk factors of HM oncogenesis in SLE patients are still under investigation. The aim of this study was to explore clinical characteristics, risk factors, and prognosis of SLE patients with or without HM in the Chinese population. Methods A retrospective, case-controlled study was conducted in 72 SLE patients between January 2013 and December 2020. Clinical and laboratory data were collected and compared between the two groups of patients with HM and those without HM. Logistic regression analysis was performed to determine risk factors of HM oncogenesis. The survival rate was estimated by Kaplan-Meier methods and Cox proportional hazards regression analysis. Results Among 72 SLE patients in this study, fifteen complicated with HM and 57 without HM were identified. The incidence rate of HM was approximately 0.24% with elevated standardized incidence ratios of lymphoma and leukemia (27.559 and 12.708, respectively). Patients with HM were older when diagnosed with SLE, with a higher frequency of infection and splenomegaly, lower levels of hemoglobin and high-density lipoprotein compared with those without HM. Fewer patients with HM expressed positive anti-dsDNA antibody (26.7% vs 66.7%, P = 0.005) or received hydroxychloroquine treatment (40.0% vs 86.0%, P = 0.001). Older age at SLE diagnosis (OR=1.122, 95% CI: 1.037–1.214) was regarded as an independent risk factor of HM oncogenesis. Female (RR= 0.219, 95% CI: 0.070–0.681) and hydroxychloroquine (RR= 0.281, 95% CI: 0.094–0.845) were protective factors of mortality in SLE patients. Conclusions SLE patients with an older age are at an increased risk of HM carcinogenesis. The prognosis of male patients with SLE tends to be poorer whether complicated with HM. The association of antinuclear antibody spectrum, medication, and HM oncogenesis in SLE needs further investigation.

Objectives Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug.Methods Patients were randomised (2:1) to tofacitinib 5 mg twice daily (N=136) or placebo (N=68); switched to tofacitinib 5 mg twice daily after month (M)3 (blinded). Primary endpoint: American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included: ACR20/50/70 response; change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI); ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout.Results The primary endpoint was met (tofacitinib 5 mg twice daily, 38.2%; placebo, 5.9%; p

Objective Infection is a major cause of death in patients with SLE. This study aimed to explore the infection rate in patients with SLE receiving a low dose of intravenous cyclophosphamide (IV-CYC).Methods Clinical parameters of 1022 patients with SLE from 24 hospitals in China were collected. Patients were divided into the short-interval and lower-dose (SILD, 400 mg every 2 weeks) IV-CYC group and the high-dose (HD, 500 mg/m2 of body surface area every month) IV-CYC group. The clinical data and infection rate between the two groups were compared.Results Compared with HD IV-CYC, the infection rate of the SILD IV-CYC group was significantly lower (13.04% vs 22.27%, p=0.001). Respiratory tract infection (10.28% vs 15.23%, p=0.046) and skin/soft tissue infection (1.78% vs 4.3%, p=0.040) were significantly decreased in the SILD IV-CYC group. Moreover, infections occurred most likely in patients with SLE with leucopenia (OR 2.266, 95% CI 1.322 to 3.887, p=0.003), pulmonary arterial hypertension (OR 2.756, 95% CI 1.249 to 6.080, p=0.012) and >15 mg/day of glucocorticoid (OR 2.220, 95% CI 1.097 to 4.489, p=0.027).Conclusions SILD IV-CYC showed a lower frequency of infection events than high-dose IV-CYC in patients with SLE.

BackgroundSystemic lupus erythematosus (SLE) can significantly influence patients’ quality of life and subjective well-being (SWB), but the relationships between clinical characteristics, SWB, and related psychological factors have been little studied.ObjectiveTo measure SWB in patients with SLE and examine how major clinical determinants, emotional variables, and related positive factors affect SWB.MethodsOverall, 1,110 patients with SLE from the Chinese SLE Treatment and Research Group (CSTAR) and 198 age and gender-matched individuals from the general population without self-reported SLE were invited to complete questionnaires of SWB evaluated by the satisfaction with life scale (SWLS), emotional variables assessed by the patient health questionnaire-9 (PHQ-9), and general anxiety disorder-7 (GAD-7) and related positive factors assessed by the self-esteem scale (SES), general self-efficacy scale (GESE), and Connor-Davidson resilience scale (CD-RISC). The multivariate linear regression was used to examine the relationship between clinical manifestations and SWB.ResultsLife satisfaction was significantly lower (p < 0.001) in patients with SLE than in the general population. Active skin involvement (OR = 0.923, 95% CI = 0.868–0.981, p < 0.05) was negatively associated with life satisfaction scores, and age at enrollment (OR = 1.160, 95% CI = 1.092–1.230, p < 0.001) were positively associated with life satisfaction scores in the multivariate regression model. The cumulative organ damage was significantly associated with depression (OR = 1.085, 95% CI = 1.022–1.153, p < 0.01) and the loss of self-esteem (OR = 1.067, 95% CI = 1.004–1.133, p < 0.05).ConclusionSWB provides useful insight into the impact of SLE on psychological health and opportunities to improve quality of life and clinical care.

ObjectiveThe aim of this review is to provide guidance on the selection of approaches to the screening and assessment of enthesitis in patients with spondyloarthritis (SpA).MethodsTwenty-four questions regarding the approaches to the screening and assessment of enthesitis and the implementation details were devised, followed by a systemic literature review. The Grading of Recommendations Assessment, Development, and Evaluation methodology was employed in the development of this guideline, with modifications to evaluate non-interventional approaches under comprehensive consideration of costs, accessibility, and evidence strength. A consensus from the voting panel was required for the inclusion of the final recommendations and the strength of each recommendation.ResultsSeventeen recommendations (including five strong recommendations) were included in this guideline. The voting panel expressed unequivocal support for the necessity of screening and assessment of enthesitis in patients with SpA. It was agreed unanimously that symptom evaluation and physical examination should serve as the initial steps to the recognition of enthesitis, whereas Maastricht Ankylosing Spondylitis Enthesitis Score is a reliable tool in both clinical trials and daily medical practice. Ultrasound examination is another reliable tool, with power Doppler ultrasound as an informative addition. Notwithstanding its high resolution, MRI is limited by the costs and relatively low accessibility, whereas radiographs had low sensitivity and therefore should be rendered obsolete in the assessment of enthesitis. PET/CT was strongly opposed in the detection of enthesitis.ConclusionThis guideline provides clinicians with information regarding the screening and assessment of enthesitis in patients with SpA. However, this guideline does not intend on dictating choices, and the ultimate decisions should be made in light of the actual circumstances of the facilities.

Abstract Background Relapsing polychondritis (RPC) is a rare autoimmune disease and its early diagnosis remains challenging. Defining the clinical patterns and disease course may help early recognition of RPC. Results Sixty-six males and 60 females were included in this study. The average age at onset were 47.1 ± 13.8 years and the median follow-up period was 18 months. Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r = − 0.75, P

Abstract Background Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN. Methods Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining. Results 159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in the renal tissues of patients with LN (P = 0.014). Bio-informatics analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R 2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-β1 (TGF-β1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018). Conclusion Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.

Abstract Background Anti-melanoma differentiation-associated protein-5 (anti-MDA5) positive patients are characterized by the high mortality rate caused by interstitial lung disease (ILD). We conducted a retrospective study to summarize the clinical features and identify the initial predictors for death in anti-MDA5 positive patients. Methods We designed a retrospective cohort of anti-MDA5 positive patients. The demographic and clinical data recorded on first admission, as well as the outcomes during the first six months follow-up, were collected. Predictors of rapidly progressive ILD (RPILD) and poor outcomes were calculated using logistic regression models and Cox proportional hazard regression models, respectively. Results A total of 90 anti-MDA5 positive patients were included in this study. Eighty-one (90%) patients presented ILD on admission and 35 (38.9%) patients developed RPILD subsequently. During the first six months of follow-up, 22 (24.4%) patients died of respiratory failure at an average time of 6.6 ± 5.9 weeks. Factors including disease duration 1600 U/ml (HR 3.7, 95% CI 1.5–9.1, P = 0.004) and CRP > 5.8 mg/L (HR 3.7, 95% CI 1.0–12.8, P = 0.044) were poor prognostic risk factors, however initial combined treatment (HR 0.3, 95% CI 0.1–0.8, P = 0.019) predicted good prognosis in anti-MDA5 positive patients. Conclusion Anti-MDA5 positive patients demonstrated a high prevalence of ILD on admission, leading to a high short-term mortality rate. Higher total GGO score, higher levels of initial KL-6 and CRP predict poor outcome in anti-MDA5 positive patients. However, initial intensive treatment may improve the prognosis.

Evidence of active tuberculosis (ATB) in patients with rheumatic diseases are research priorities but limited data from China have been reported. Research targeting patients not taking anti-TNF biologics are especially insufficient. We aimed to investigate the prevalence and risk factors of ATB in this at-risk population. We conducted a tertiary hospital-based, multi-center, cross-sectional study by using stratified multi-stage cluster sampling strategy to screen ATB in patients with rheumatic diseases. We estimated the prevalence of ATB in patients with rheumatic diseases and identified risk factors among those who were not taking anti-TNF biologic. A total of 13,550 eligible patients were enrolled, and the result showed the standardized prevalence of ATB according to the composition ratio of various types of rheumatic disease was 882/100000 (95% confidence interval (CI): 706-1057). Multivariable logistic regression analysis in patients not taking anti-TNF biologics showed that the independent risk factors of ATB were having systemic lupus erythematosus (SLE) (OR=2.722, 95% CI: 1.437-5.159, p=0.002), having Behcet’s disease (BD) (OR= 5.261, 95% CI: 2.071-13.365, p

BackgroundSerum uric acid (SUA) is associated with many cardiovascular risk factors, such as metabolic syndrome (MetS) and subclinical atherosclerosis. However, the relationship of SUA with carotid atherosclerosis remains controversial. We aimed to investigate whether elevated SUA levels are associated with a high risk of carotid atherosclerosis and MetS in patients with type 2 diabetes mellitus (T2DM).MethodsThis cross-sectional study was performed with a sample of 1,947 hospitalized patients with T2DM. Carotid intima-media thickness and carotid artery plaques were measured via Doppler ultrasound.ResultsUric acid levels were negatively associated with HbA1C, eGFR, and HDL-C (all P < 0.001) and positively associated with WBC, BMI, ACR, creatinine, total cholesterol, triglycerides, LDL-C, systolic blood pressure, and diastolic blood pressure (all P < 0.001). After adjusting for multiple potential confounders, the risks were substantially higher for MetS in the highest quartile of SUA levels (odds ratio: 2.91, 95% confidence interval: 1.54–5.51, P = 0.003 for trend) than in the lowest quartile of SUA levels. Furthermore, a significant increase was observed in the prevalence of overweight/obesity, hypertension, and dyslipidemia across the SUA quartiles independent of confounders. However, no significant association was found between SUA quartile with the presence of carotid atherosclerosis.ConclusionsIn patients with T2DM, SUA levels were closely associated with MetS and its components but not with carotid atherosclerosis.

ObjectiveThis study aimed to investigate the association of serum bone turnover markers (BTMs) with metabolic syndrome components and carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM).MethodsWe performed a cross-sectional based study in T2DM populations. Serum BTMs including N-terminal osteocalcin (N-MID), β-cross-linked C-telopeptide of type I collagen (β-CTX), and procollagen type I N-terminal propeptide (PINP) were measured by immunoassay method. Carotid artery intima-media thickness and carotid artery plaque (CAP) were measured by B-mode ultrasound.ResultsThe serum N-MID, PINP, and β-CTX levels significantly lower in the CAP group compared with the non-CAP group. N-MID and PINP levels were inversely associated with fasting blood glucose, HOMA-IR, CRP, eGFR, and triglycerides (all P < 0.05), whereas β-CTX levels were negatively associated with triglycerides (P < 0.05). After multiple adjustment, the odds ratios (ORs) were substantially higher for CAP with decreased N-MID level (OR = 0.958; 95% CI = 0.926–0.991; P = 0.013). However, serum levels of PINP and β-CTX were not associated with the presence of CAP. Multivariate logistic regression analysis further revealed that serum N-MID, PINP, and β-CTX levels were significantly associated with hypertriglyceridemia, whereas serum N-MID and β-CTX levels were associated with overweight/obesity risk.ConclusionsThese findings indicated that serum N-MID level was an independent risk factor for carotid atherosclerosis, whereas BTM levels were associated with other metabolic syndrome components in a T2DM population.

Abstract Background Systemic lupus erythematosus (SLE) is associated with increased risk of cancer and the mechanism remains unclear. Here, we examined the level of auto-antibodies and disease activity index scores in SLE patients with cancers and analyzed whether medications for SLE management might contribute to the higher cancer risk in SLE patients. Methods In this retrospective study, we carried out a nested case-control study in a large cohort of SLE patients. We screened 5858 SLE patients to identify the newly diagnosed and yet to be treated cancers. The following clinical features were evaluated: auto-antibodies levels, SLE disease activity index scores, and previous medication used for SLE management. Systemic glucocorticoid, cyclophosphamide, hydroxychloroquine (HCQ), methotrexate, and azathioprine were considered the main medication indices. Results Our analyses identified 51 SLE patients who also had cancer and 204 matched control patients who had SLE but not cancer. Of the 51 SLE patients, thyroid cancer (14/51, 27.45%), cervical cancer (10/51, 19.61%), and lung cancer (7/51, 13.73%) were the most common types. Our analyses did not reveal any significant differences in the levels of auto-antibodies in SLE patients with cancers relative to the control group. Further, we observed that disease activity was significantly lower in SLE patients with cancers relative to the matched control SLE group. There was no statistically significant association between the cancer risk and the use of systemic glucocorticoid, cyclophosphamide, methotrexate, or azathioprine. Importantly, the administration of HCQ was significantly lower in SLE patients suffering cancers relative to the cancer-free matched control group. Conclusions Our analyses indicate that SLE patients with cancers might have a lower disease activity at the time of cancer diagnosis. HCQ was negatively associated with cancer risk in SLE patients. These findings highlight a potential and novel prevention strategy for SLE.

Statins are an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Growing evidence indicates that statins may have an anti-inflammatory effect. Whether genetically proxied HMGCR inhibition can reduce the risk of ankylosing spondylitis is unknown. We constructed an HMGCR genetic score comprising nearly randomly inherited variants significantly associated with LDL cholesterol levels within ± 100 kb from HMGCR to proxy for inhibition of HMGCR. We also constructed PCSK9 and NPC1L1 scores as well as the LDL polygenetic score to proxy for the inhibition of these drug targets as well as serum LDL cholesterol levels, respectively. We then compared the associations of these genetic scores with the risk of ankylosing spondylitis. Of 33,998 participants in the primary cohort, 12,596 individuals had been diagnosed with ankylosing spondylitis. Genetically proxied inhibition of HMGCR scaled to per mmol/L decrease in LDL cholesterol levels by the HMGCR score was associated with a lower risk of ankylosing spondylitis (OR, 0.57; 95% CI, 0.38–0.85; P value = 5.7 × 10–3). No significant association with ankylosing spondylitis was observed for the PCSK9 score (OR, 0.89; 95% CI, 0.68–1.16) and the NPC1L1 score (OR, 1.50; 95% CI, 0.39–5.77). For the LDL score, genetically determined per mmol/L decrease in LDL cholesterol levels led to a reduced risk of ankylosing spondylitis (OR, 0.64; 95% CI, 0.43–0.94), with significant heterogeneity and pleiotropy in the estimate. Exploratory analyses showed that genetically proxied inhibition of HMGCR appeared to have a similar effect to long-term statin therapy in modifying the risk of coronary artery disease and type 2 diabetes, suggesting that the HMGCR score might be a reliable model to assess the effect of statin. Genetically proxied inhibition of HMGCR was associated with a decreased risk of ankylosing spondylitis. This mechanism-based estimate was in line with existing observations suggesting the clinical benefits of statin therapy for ankylosing spondylitis.

Background: Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) may require intensive care unit (ICU) admission due to different reasons, and the in-ICU mortality is high among AAV patients. The aim of this study was to explore the clinical features and risk factors of mortality of patients with AAV in the ICU.Methods: A retrospective study was conducted based on 83 AAV patients admitted to the ICU in a tertiary medical institution in China. Data on clinical characteristics, laboratory tests, treatment in ICU and outcomes were collected. The data were analyzed using univariate and multivariate logistic regression analysis to explore the variables that were independently related to mortality. Kaplan–Meier method was used to assess the long-term survival.Results: Among the 83 patients, 41 (49.4%) were female. The mean age of patients was 66 ± 13 years. Forty-four patients deceased, with the in-ICU mortality of 53%. The most common cause for ICU admission was active vasculitis (40/83, 48.2%). The main cause of death was infection (27/44, 61.4%) followed by active vasculitis (15/44, 34.1%). A multivariate analysis revealed that the Acute Physiology and Chronic Health Evaluation II (APACHE II) at ICU admission (OR = 1.333, 95% CI: 1.031–1.722) and respiratory failure (OR = 620.452, 95% CI: 11.495–33490.306) were independent risk factors of in-ICU death. However, hemoglobin (OR = 0.919, 95% CI: 0.849–0.995) was an independent protective factor. The nomogram established in this study was practical in predicting the risk of in-ICU mortality for AAV patients. Moreover, for 39 patients survived to the ICU stay, the cumulative survival rates at 0.5, 1, and 5 years were 58.3%, 54.2%, and 33.9%, respectively, and the median survival time was 14 months.Conclusion: In our study, active vasculitis was the most frequent reason for ICU admission, and the main cause of death was infection. APACHE II and respiratory failure were independent risk factors while hemoglobin was an independent protective factor of in-ICU mortality for AAV patients admitted to the ICU. The risk prediction model developed in this study may be a useful tool for clinicians in early recognition of high-risk patients and applying appropriate management.

Background: Patients with systemic lupus erythematosus (SLE) may sometimes require admission to the intensive care unit (ICU), and the outcome is poor. The aim of this study was to explore the clinical features of patients with SLE in the ICU, identify prognostic factors, and develop and evaluate a prognostic model to predict in-ICU mortality of patients with SLE.Patients and Methods: This was a single center retrospective study in a tertiary medical institution in China. A total of 480 SLE patients with 505 ICU admissions from 2010 to 2019 were screened, and 391 patients were enrolled. The clinical feature and outcomes of the patients were analyzed. According to the random number table, patients were divided into two mutually exclusively groups named derivation (n = 293) and validation (n = 98). Prognostic factors were identified by a Cox model with Markov Chain Monte Carlo simulation and evaluated by latent analysis. The risk score was developed based on the derivation group and evaluated using the validation group.Results: Among the 391 patients, 348 (89.0%) patients were females. The median age of patients was 34 years, and the median course of SLE was 6 months. The median APACHE II and SLEDAI were 17 and 10, respectively. The average in-ICU mortality was 53.4% (95% CI, 48.5–58.4%). A total of 186 patients were admitted to the ICU due to infection. Pneumonia (320/391, 81.8%) was the most common clinical manifestation, followed by renal disease (246/391, 62.9%). Nine prognostic factors were identified. The model had C statistic of 0.912 (95% CI, 0.889–0.948) and 0.807 (95% CI 0.703–0.889), with predictive range of 5.2–98.3% and 6.3–94.7% for the derivation and validation groups, respectively. Based on distribution of the risk score, 25.3, 49.5, and 25.2% of patients were stratified into the high, average, and low-risk groups, with corresponding in-ICU mortality of 0.937, 0.593, and 0.118, respectively.Conclusion: Nine prognostic factors including age, white blood cell count, alanine transaminase, uric acid, intracranial infection, shock, intracranial hemorrhage, respiratory failure, and cyclosporin A/tacrolimus usage were identified. A prognostic model was developed and evaluated to predict in-ICU mortality of patients with SLE. These findings may help clinicians to prognostically stratify patients into different risk groups of in-ICU mortality, and provide patients with intensive and targeted management.