A prognostic model for systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study.

BACKGROUND: Pulmonary arterial hypertension is a major cause of death in systemic lupus erythematosus, but there are no tools specialized for predicting survival in systemic lupus erythematosus-associated pulmonary arterial hypertension. RESEARCH QUESTION: To develop a practical model for predicting long-term prognosis in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. METHODS: A prognostic model was developed from a multicenter, longitudinal national cohort of consecutively evaluated patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. The study was conducted between November 2006 and February 2020. All-cause death was defined as the endpoint. Cox regression and least absolute shrinkage and selection operators were used to fit the model. Internal validation of the model was assessed by discrimination and calibration using bootstrapping. RESULTS: Of 310 patients included in the study, 81 (26.1%) died within a median follow-up of 5.94 years (interquartile range 4.67-7.46). The final prognostic model included eight variables: modified World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, estimated glomerular filtration rate, thrombocytopenia, mild interstitial lung disease, N-terminal pro-brain natriuretic peptide/brain natriuretic peptide level, and direct bilirubin level. A 5-year death probability predictive algorithm was established and validated using the C-index (0.77) and a satisfactory calibration curve. Risk stratification was performed based on the predicted probability to improve clinical decision-making. CONCLUSIONS: This new risk stratification model for systemic lupus erythematosus-associated pulmonary arterial hypertension may provide individualized prognostic probability using readily obtained clinical risk factors. External validation is required to demonstrate the accuracy of this model's predictions in diverse patient populations.

Management of Rheumatoid Arthritis With a Digital Health Application: A Multicenter, Pragmatic Randomized Clinical Trial.

IMPORTANCE: Digital health applications have been shown to be effective in the management of chronic diseases with simple treatment targets. The potential clinical value of digital health applications in rheumatoid arthritis (RA) has not been well studied. OBJECTIVE: To investigate whether assessing patient-reported outcomes using digital health applications could result in disease control for patients with RA. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, open-label randomized clinical trial in 22 tertiary hospitals across China. Eligible participants were adult patients with RA. Participants were enrolled from November 1, 2018, to May 28, 2019, with a 12-month follow-up. The statisticians and rheumatologists who assessed disease activity were blinded. Investigators and participants were not blind to group assignment. Analysis was conducted from October 2020 to May 2022. INTERVENTIONS: Participants were randomly assigned at a 1:1 ratio (block size of 4) to a smart system of disease management group (SSDM) or a conventional care control group. Upon the completion of the 6-month parallel comparison, patients in the conventional care control group were instructed to use the SSDM application for an extension of 6 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of patients with disease activity score in 28 joints using the C-reactive protein (DAS28-CRP) of 3.2 or less at month 6. RESULTS: Of 3374 participants screened, 2204 were randomized, and 2197 patients with RA (mean [SD] age, 50.5 [12.4] years; 1812 [82.5%] female) were enrolled. The study included 1099 participants in the SSDM group and 1098 participants in the control group. At month 6, the rate of patients with DAS28-CRP of 3.2 or less was 71.0% (780 of 1099 patients) in the SSDM group vs 64.5% (708 of 1098 patients) in the control group (difference between groups, 6.6%; 95% CI, 2.7% to 10.4%; P = .001). At month 12, the rate of patients with DAS28-CRP of 3.2 or less in the control group increased to a level (77.7%) that was comparable with that (78,2%) in the SSDM group (difference between groups, -0.2%; 95% CI, -3.9% to 3.4%; P = .90). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of RA, the use of a digital health application with patient-reported outcomes was associated with an increase in disease control rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03715595.

Risk assessment in systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study.

Objective: This study evaluated the prognostic value of the multivariable risk assessment for systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH). Methods: A multicenter prospective cohort of SLE-associated PAH (CSTAR-PAH cohort) diagnosed based on right heart catheterization (RHC) was established. Baseline and follow-up records were collected. Three methods of risk assessment, including (1) the number of low-risk criteria, based on World Health Organization functional class (WHO FC), 6-min walking distance (6MWD), right atrial pressure (RAP), and cardiac index (CI); (2) the three-strata stratification based on the average risk score of four variables (WHO FC, 6MWD, RAP, and CI); and (3) the four-strata stratification based on COMPARE 2.0 model were applied. A risk-assessment method using three noninvasive low-risk criteria was applied at the first follow-up visit. Survival curves between patients with different risk groups were compared by Kaplan-Meier's estimation and log-rank test. Results: Three-hundred and ten patients were enrolled from 14 PAH centers. All methods of stratification at baseline and first follow-up significantly discriminated long-term survival. Survival rates were also significantly different based on the noninvasive risk assessment in first follow-up visit. Survival deteriorated with the escalation of risk from baseline to first follow-up. Patients with baseline serositis had a higher rate of risk improvement in their follow-up. Conclusion: The risk assessment has a significant prognostic value at both the baseline and first follow-up assessment of SLE-associated PAH. A noninvasive risk assessment can also be useful when RHC is not available during follow-up. Baseline serositis may be a predictor of good treatment response in patients with SLE-associated PAH.

Comparison of the efficacy and safety of the adalimumab biosimilar TQ-Z2301 and adalimumab for the treatment of Chinese patients with active ankylosing spondylitis: a multi-center, randomized, double-blind, phase III clinical trial.

OBJECTIVE: To assess the clinical equivalence of TQ-Z2301, a biosimilar of adalimumab, to the reference adalimumab in the treatment of Chinese patients with active ankylosing spondylitis. METHODS: This multicenter, randomized, double-blind, positive-controlled phase III clinical trial was conducted in 19 centers across China. Chinese adults with active ankylosing spondylitis despite being treated with non-steroidal anti-inflammatory drugs for ≥ 4 weeks were randomized in a 1:1 ratio to subcutaneously receive 40 mg of TQ-Z2301 or adalimumab every other week for 24 weeks. The primary endpoint was the percentage of patients who achieved at least 20% improvement according to the Assessment of Spondyloarthritis International Society criteria (ASAS20) at week 24. The equivalence was established if the 90% CI for RR of ASAS20 between two groups at week 24 fell within (0.80, 1.25). Secondary endpoints included efficacy measures of disease activity, spinal mobility, physical function and quality of life, immunogenicity, and pharmacokinetic parameters. Safety analysis was done for all patients who received at least one study drug. RESULTS: A total of 380 patients were enrolled in the study between September 2018 and October 2019, including 188 in the TQ-Z2301 group and 192 in the adalimumab group. In the full analysis population, the ASAS20 response rate at week 24 was 86.70% in the TQ-Z2301 group, and 80.73% in the adalimumab group, the RR of ASAS20 for TQ-Z2301 versus adalimumab was 1.074, 90% CI (0.997, 1.157), fell within the predefined equivalence boundary (0.80, 1.25). Except for the SF-36 at week 12, there was no statistical difference between the two groups for all the secondary endpoints (P>0.05). The incidence of adverse events group was 82.45% in the TQ-Z2301, and 83.85% in the adalimumab group, the safety profile of the two groups was similar. The profiles of immunogenicity and pharmacokinetics were also similar between the two groups. CONCLUSION: TQ-Z2301 is equivalent to adalimumab for the treatment of Chinese patients with active ankylosing spondylitis. The safety, immunogenicity, and pharmacokinetic characteristics of both drugs are similar. TRIAL REGISTRATION: The study (CTR20181863) was registered in the Chinese Clinical Trial Registry on 19 October 2018. Key Points • TQ-Z2301 showed the equivalence of efficacy compared with the reference adalimumab for the treatment of Chinese patients with active ankylosing spondylitis. • The safety, immunogenicity, and pharmacokinetics profiles of TQZ-2301 were similar to those of the reference adalimumab.

miR-150-5p inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by targeting VDR.

Dysregulated microRNAs (miRNAs or miRs) serve potential roles in inflammatory systemic disease, including ankylosing spondylitis (AS). The aim of the present study was to investigate the potential function of miR-150-5p in osteogenic differentiation of AS fibroblasts and its underlying mechanism. The expression of miR-150-5p and vitamin D receptor (VDR) in AS joint capsules and fibroblasts was detected by reverse transcription-quantitative (RT-q)PCR and western blotting. Following overexpression of miR-150-5p, the alteration in osteogenic gene expression was detected by RT-qPCR, western blotting and alkaline phosphatase activity assay, as well as alizarin red staining. The association between miR-150-5p and VDR was confirmed by luciferase assay and rescue experiments were performed. Patients with AS exhibited decreased expression of miR-150-5p in joint capsules. Treatment with bone morphogenic protein 2 (BMP-2) and transforming growth factor-ß1 (TGF-ß1) led to downregulation of miR-150-5p in AS fibroblasts. Enforced expression of miR-150-5p attenuated osteogenic differentiation of AS fibroblasts. These results demonstrated that miR-150-5p inhibited osteogenic differentiation of AS fibroblasts by targeting VDR. miR-150-5p overexpression decreased osteogenic transformation of fibroblasts by decreasing VDR expression in AS.

Uric acid, as a double-edged sword, affects the activity of epidermal growth factor (EGF) on human umbilical vein endothelial cells by regulating aging process.

Uric acid (UA) is the main metabolite of the human body. Although UA is only a product of metabolism, it is important biological regulator. Epidermal growth factor (EGF) has important biological functions. However, so far, the effect of UA on EGF's activity has not been revealed. For this, in the current study, we systematically studied the effect of OA on the biological activity of EGF. Human Umbilical Vein Endothelial Cells (HUVECs) were used as an in vitro model, and Western-blot, RT-PCR, laser scanning confocal microscopy (CLSM) and co-localization analyses were carried out. The results showed that high concentration of UA (10 mg/dl) severely affected the biological activity of EGF. High concentration of UA suppressed the activity of EGF, and inhibited the biological effect of EGF on the HUVECs. However, it is interesting that EGF-mediated intracellular signaling was significantly down-regulated in the H2O2-induced senescent HUVEC, and physiological concentration of UA could at least partially restore the EGF-mediated signaling. Further work showed that physiological concentration of UA (5 mg/dl) shows the anti-aging effect. Taken together, current research indicates that UA may be a 'double-edged sword', physiological concentration of UA may be beneficial, but high concentrations of uric acid (UA) are harmful.

Prevalence and risk factors of active tuberculosis in patients with rheumatic diseases: a multi-center, cross-sectional study in China.

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<0.001), taking azathioprine(AZA) within the past two years (OR=2.095, 95% CI: 0.986-4.450, p=0.054), exposing to glucocorticoids ≥30mg/d for more than four weeks within the past two years (OR=2.031, 95% CI: 1.247-3.309, p=0.004) and having evidences of previous TB (OR= 6.185, 95% CI: 3.487-10.969, p<0.001). The prevalence of ATB was higher in patients with rheumatic diseases compared to the general population. Patients with SLE or BD, prolonged exposure to moderate to high dose of glucocorticoids and previous TB were independent risk factors for ATB.

Tripterygium wilfordii derivative LLDT-8 targets CD2 in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA), a chronic inflammatory synovitis systemic disease, can lead to joint deformities, loss of function and even death. The pathogenesis of RA may be related to genetics, infection and/or sex hormones; however, detailed accounts of the molecular mechanisms underlying its pathogenesis are lacking. In the present study, the synovial tissues of patients with RA and healthy individuals were analyzed to identify the pathogenic signaling pathways and key candidate genes involved in RA. Gene Ontology (GO), pathway enrichment and protein-protein interaction analysis were further used to identify the differentially expressed genes (DEGs) and their potential roles in RA. Molecular docking was used to screen the potential candidate drugs for management of RA. Small interfering RNA was used for knockdown of the CD2 protein. A Cell Counting Kit-8 assay was used to detect the proliferation of cells. Changes in the levels of inflammatory cytokines were detected using ELISA. A total of 279 DEGs were identified in RA; amongst these genes, 166 and 113 were upregulated and downregulated, respectively. GO analysis revealed that the upregulated DEGs were primarily enriched in the activation of the immune and adaptive immune responses, as well as the inflammatory response. The T-cell surface antigen CD2 (CD2) was identified as the most important hub gene by selecting the most important module from the protein-protein interaction network. Knockout of CD2 reduced the damaging effects of TNF-α on synovial cells. Through in situ screening using computer-aided drug design, the triptolide derivative (5R)-5-hydroxytriptolide (LLDT-8) was determined to have the highest docking score based on the CD2 protein structure. Cell experiments showed that LLDT-8 could inhibit the expression of CD2. Cell proliferation and inflammatory cytokine assays confirmed that CD2 was the direct target of LLDT-8. Together, the results of the present study determined factors involved in the pathogenesis of RA and the important role of CD2 in this process by analyzing the DEGs in the RA process. LLDT-8 inhibited CD2 and may thus be used to treat RA. These candidate genes and signaling pathways may serve as potential targets for the clinical treatment of RA.

Prevalence of metabolic syndrome in patients with rheumatoid arthritis in eastern China-A hospital based study.

OBJECTIVE: The purpose of this hospital clinic based study was to evaluate the potential risk factors associated with the prevalence of MetS in RA population. METHODS: From January 2015 to October 2018, 717 patients with RA and 717 healthy controls who were treated or performed physical examination in Tianjin First Central Hospital were enrolled in this study. The basic disease diagnoses were recorded. A questionnaire was performed on all participants to assess the demographic details of the RA cohort. Moreover, laboratory indicators related to glucose and lipid metabolism in patients with RA were also detected. The potential risk factors for MetS were also analyzed. RESULTS: The prevalence of MetS were 31.2% and 34.2% in case and control groups, respectively (P = .22). There were lower levels of HDL-C, obesity, TG, LDL-C and TC in case group than control group (all P < .05). The hypertension levels in healthy controls was decreased in compared with patients with RA (P < .05). Nevertheless, in patients with RA, complement 3 (OR: 1.02; 95% CI: 1.01-1.03, P = .007) and less glucocorticoids use (OR: 0.63, 95% CI: 0.39-0.99, P = .046) were associated with MetS. CONCLUSION: The prevalence of MetS was not associated with RA. Complement 3 may be associated with the higher prevalence of MetS in patients with RA. Glucocorticoids treatment may be associated with MetS.

Validation of the REVEAL Prognostic Models in Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension.

No previous studies have investigated the predictive performance of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) prognostic equation and simplified risk score calculator in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). We aimed to validate these prediction tools in an external cohort of patients with SLE-PAH. In this study, the validation cohort consisted of patients with SLE-PAH registered in a prospective, multicenter, nationwide database between November 2006 and May2016. The follow-up of patients was censored at 1 year. Discrimination, calibration, model fit, and risk stratification of the REVEAL prognostic equation and simplified risk score calculator were validated. As a result, a total of 306 patients with SLE-PAH were included. The 1-year overall survival rate was 91.5%. The C-index of the prognostic equation was 0.736, demonstrating reasonably good discrimination, and it was greater than that for the simplified risk score calculator (0.710). The overall calibration slope was 0.83, and the Brier score was 0.079. The risk of renal insufficiency and World Health Organization Functional Class III (WHO FC III) were underestimated, and the risk assigned to a heart rate >92 bpm in the REVEAL prognostic models was not observed in our validation cohort. Both model discrimination and calibration were poor in the very high-risk group. In conclusion, the REVEAL models exhibit good discriminatory ability when predicting 1-year overall survival in patients with SLE-PAH. Findings from both models should be interpreted with caution in cases of renal insufficiency, WHO FC III, and heart rate >92 bpm.

Experimental Study of Nanostructured Lipid Carrier in the Treatment of Immune Lupus Nephritis.

Lupus nephritis (LN) is a common, frequently-occurring and refractory renal medical disease. With the progress of society, the improvement of people's living standards, changes in lifestyles, and drug abuse, the incidence rate is increasing year by year. The effect of treatment on it is currently unsatisfactory clinically, and the recurrence rate is relatively high, which seriously affects People's quality of life. Therefore, the disease has become a hot and difficult point of research. In recent years, the pathogenesis and treatment of this disease have been thoroughly studied at home and abroad, especially the application of hormones and cyclophosphamide, which have achieved relatively good clinical effects. In this paper, nanostructured lipid carriers were prepared and their pharmacodynamics were studied in the treatment of mice with immunological lupus nephritis. The main experimental methods and results show that the nanostructured lipid carrier TWHF-NLC prepared by the high-pressure microjet method is characterized by transmission electron microscopy, and the TP-NLC has a uniform particle size, and the nanoparticles are spherical or short rod-shaped. Animal experiments show that TWHF-NLC has obvious therapeutic effect on mice with immune lupus nephritis. Pathological sections of the kidney showed that TWHF-NLC can effectively reduce the collagen content of the renal interstitial cells, and remove MCP-1 deposited in the kidney, and inhibit its expression.

Serum progranulin level is associated with disease activity following orthopedic surgery in rheumatoid arthritis patients.

BACKGROUND: Few studies have focused on the ability of progranulin to predict postoperative disease activity in rheumatoid arthritis (RA) patients who have undergone surgery. This study evaluated serum progranulin levels in active RA patients and analyzed its relationship with postoperative disease activity. METHODS: One hundred thirty-two patients with active RA and 72 healthy subjects were included in this study. Serum progranulin was measured, and clinical data were collected. The postoperative 1-year Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) scores was evaluated as an indicator of disease activity. The predictive value of progranulin in postoperative 1-year disease activity in RA patients was also analyzed. RESULTS: Serum progranulin was significantly associated with the postoperative 1-year RA disease activity. The mean serum progranulin level in patients with a high disease activity was significantly higher than that of RA patients with low-to-moderate disease activity (54.2 ± 10.6 ng/mL vs. 46.7 ± 8.8 ng/mL). Serum progranulin was also evaluated as an independent predictive factor for postoperative 1-year RA disease activity in multivariate analysis (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.02-8.85). CONCLUSIONS: Serum progranulin levels may be a promising indicator of postoperative disease activity in RA patients who underwent orthopedic surgery.

Pulmonary arterial hypertension associated with primary Sjögren's syndrome: a multicentre cohort study from China.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an important cause of pulmonary arterial hypertension (PAH), which remains insufficiently studied and needs attention. This study aimed to investigate the clinical characteristics, risk factors, prognosis and risk assessment of pSS-PAH. METHODS: We established a multicentre cohort of pSS-PAH diagnosed by right heart catheterisation. The case-control study was conducted with pSS-non-PAH patients as a control group to identify the risk factors for PAH. In the cohort study, survival was calculated, and risk assessment was performed at both baseline and follow-up visits. RESULTS: In total, 103 patients with pSS-PAH were enrolled, with 526 pSS-non-PAH patients as controls. The presence of anti-SSB (p<0.001, OR 4.095) and anti-U1RNP antibodies (p<0.001, OR 29.518), the age of pSS onset (p<0.001, OR 0.651) and the positivity of corneal staining (p=0.003, OR 0.409) were identified as independent risk factors for PAH. The 1-, 3- and 5-year survival rates were 94.0%, 88.8% and 79.0%, respectively. Cardiac index (p=0.010, hazard ratio (HR) 0.161), pulmonary vascular resistance (p=0.016, HR 1.105) and Sjögren's syndrome disease damage index (p=0.006, HR 1.570) were identified as potential predictors of death in pSS-PAH. Long-term outcomes were improved in patients in the low-risk category at baseline (p=0.002) and follow-up (p<0.0001). CONCLUSION: The routine screening of PAH is suggested in pSS patients with early onset and positivity for anti-SSB or anti-U1RNP antibodies. Patient prognosis might be improved by improving reserved cardiopulmonary function, by achieving a damage-free state and especially by achieving low-risk category, which supports the treat-to-target strategy for pSS-PAH.

Drug screening and identification of key candidate genes and pathways of rheumatoid arthritis.

Rheumatoid arthritis (RA), which normally manifests as a multi­joint inflammatory reaction, is a common immunological disease in clinical practice. However, the pathogenesis of RA has not yet been fully elucidated. Rituximab (RTX) is an effective drug in the treatment of RA, however its therapeutic efficacy and mechanism of action require further investigation. Thus, the present study aimed to screen the candidate key regulatory genes and explain the potential mechanisms of RA. Gene chips of RA and normal joint tissues were analyzed and, gene chips of RTX before and after treatment were investigated. In the present study, strong evidence supporting the pathogenesis of RA and mechanism of action of RTX were also revealed. Differentially expressed genes (DEGs) were analyzed using the limma package of RStudio software. A total of 1,150 DEGs were detected in RA compared with normal joint tissues. The upregulated genes were enriched in 'interleukin­12 production', 'I­κB kinase/NF­κB signaling', 'regulation of cytokine production involved in immune response' and 'cytokine metabolic process'. Functional enrichment analysis showed that RTX was primarily involved in the inhibition of 'adaptive immune response', 'B cell activation involved in immune response' and 'immune effector process'. Subsequently, leukocyte immunoglobulin­like receptor subfamily B member 1 (LILRB1), a hub gene with high connectivity degree, was selected, and traditional Chinese medicine libraries were molecularly screened according to the structure of the LILRB1 protein. The results indicated that kaempferol 3­O­ß­D­glucosyl­(1→2)­ß­D­glucoside exhibited the highest docking score. In the present study, the DEGs and their biological functions in RA and the pharmacological mechanism of RTX action were determined. Taken together, the results suggested that LILRB1 may be used as a molecular target for RA treatment, and kaempferol 3­O­ß­D­glucosyl­(1→2)­ß­D­glucoside may inhibit the pathological process of RA.

Active vitamin D activates chondrocyte autophagy to reduce osteoarthritis via mediating the AMPK-mTOR signaling pathway.

Osteoarthritis (OA) is a common joint degenerative disease. Vitamin D (VD) is essential for bone health. We hypothesized that active VD could be used as a therapeutic treatment for OA. Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been found in patients with OA, and thus the serum level of VD could be diagnostic of OA. To test this, we established a mouse model of OA. The results from staining with hematoxylin-eosin and Safranin O - Fast Green indicated that active VD reduced the symptoms of OA in mice. The results from Western blotting indicated that treatment with VD increased the activity of the p-AMPK-AMPK signaling pathway and decreased the p-mTOR-mTOR pathway; it also increased the ratio of LC3II:LC3I antibodies and the protein expression levels of Beclin-1, but decreased the level of p62. Further, treatment with VD reduced the levels of tumor necrosis factor-α and interleukin-6 both in cartilage tissues and in chondrocytes. Administration of the AMPK inhibitor compound C and autophagy inhibitor 3-methyladenine (3-MA) reversed these changes following VD treatment. In addition, the results from transfection with mRFP-GFP-LC3 indicated that active VD led to autophagosome aggregation in OA chondrocytes. 3-MA inhibited cell autophagy and promoted inflammation in OA. This study provides evidence that active VD activate chondrocyte autophagy to reduce OA inflammation via activating the AMPK-mTOR signaling pathway. Treatment with active VD could be a novel therapeutic option for OA.

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis.

BACKGROUND: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development. METHODS: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression. RESULTS: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001). CONCLUSION: As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.

Pulmonary arterial hypertension in systemic lupus erythematosus based on a CSTAR-PAH study: Baseline characteristics and risk factors.

AIM: Pulmonary arterial hypertension (PAH) is a complex and devastating complication of systemic lupus erythematosus (SLE). We sought to describe the baseline characteristics of right heart catheterization (RHC)-confirmed SLE-associated PAH and identify risk factors for PAH in SLE patients. METHODS: A multicenter, cross-sectional study was conducted using the Chinese SLE Treatment and Research group (CSTAR) registry. Baseline data for patients with SLE-associated PAH and SLE patients without PAH were collected and compared. Risk factors for PAH among patients with SLE were identified. RESULTS: A total of 292 patients with SLE-associated PAH were enrolled. RHC was used to reveal hemodynamic features, including mean pulmonary arterial pressure (46.2 ± 12.0 mm Hg), pulmonary arterial wedge pressure (7.84 ± 3.92 mm Hg), pulmonary vascular resistance (10.86 ± 5.57 Wood units), and cardiac index (2.77 ± 0.91 L/min × m2 ). A multivariate logistic regression analysis showed that serositis (odds ratio [OR] = 5.524, 95% CI 3.605-8.465, P < 0.001), anti-ribonucleoprotein (RNP) antibody positivity (OR = 13.332, 95% CI 9.500-18.710, P < 0.001), and diffusion capacity of carbon monoxide in the lung (DLCO)/%Pred <70% (OR = 10.018, 95% CI 6.619-15.162, P < 0.001) were independent predictors of PAH. We recommend using transthoracic echocardiography (TTE) to perform early screening of SLE patients who have serositis, anti-RNP antibody positivity, or DLCO/%Pred <70%. RHC is suggested for patients suspected of having PAH. Once a diagnosis of SLE-PAH is confirmed, evaluation and treatment should immediately begin. CONCLUSION: Overall, we recommend performing early screening using TTE in SLE patients with serositis, anti-RNP antibodies, or a DLCO/%Pred <70%, even for patients in a relatively stable condition according to SLE disease activity index.

Long-term prognosis of patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study.

This study aimed to identify the long-term clinical outcomes and prognostic factors of patients with systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) confirmed by right heart catheterisation.A multicentre prospective cohort of SLE-associated PAH was established. Baseline and follow-up records were collected. The primary end-point was death. The secondary exploratory end-point was treatment goal achievement (TGA), defined as an integrated outcome.In total, 310 patients were enrolled from 14 PAH centres. The 1-, 3- and 5-year survival rates were 92.1%, 84.8% and 72.9%, respectively. The 1-, 3- and 5-year TGA rates were 31.5%, 53.6% and 62.7%, respectively. Baseline serositis, 6-min walking distance >380 m and cardiac index ≥2.5 L·min-1·m-2 were identified as independent prognostic factors of TGA. Patients with baseline serositis were more likely to reach TGA after intensive immunosuppressive therapy. TGA was identified as a positive predictor of survival in patients with SLE-associated PAH.TGA was associated with long-term survival, which supports the treat-to-target strategy in SLE-associated PAH. Baseline heart function predicted both survival and treatment goal achievement in patients with SLE-associated PAH. Patients with serositis at baseline tended to benefit from intensive immunosuppressive therapy and have a better clinical outcome.