BackgroundArtifical nerve scaffold can be used as a promising alternative to autologous nerve grafts to enhance the repair of peripheral nerve defects. However, current nerve scaffolds lack efficient microstructure and neurotrophic support.MethodsMicrosphere–Scaffold composite was developed by incorporating chitosan microspheres loaded with nerve growth factor (NGF–CMSs) into collagen-chitosan scaffolds (CCH) with longitudinally oriented microchannels (NGF–CMSs/CCH). The morphological characterizations, in vitro release kinetics study, neurite outgrowth assay, and bioactivity assay were evaluated. After that, a 15-mm-long sciatic nerve gap in rats was bridged by the NGF–CMSs/CCH, CCH physically absorbed NGF (NGF/CCH), CCH or nerve autograft. 16 weeks after implantation, electrophysiology, fluoro-gold retrograde tracing, and nerve morphometry were performed.ResultsThe NGF–CMSs were evenly distributed throughout the longitudinally oriented microchannels of the scaffold. The NGF–CMSs/CCH was capable of sustained release of bioactive NGF within 28 days as compared with others in vitro. In vivo animal study demonstrated that the outcomes of NGF–CMSs/CCH were better than those of NGF/CCH or CCH.ConclusionOur findings suggest that incorporation of NGF–CMSs into the CCH may be a promising tool in the repair of peripheral nerve defects.

Enthesitis is considered as the primary anatomical lesion in ankylosing spondylitis (AS). We aimed to investigate the potential of ultrasound to detect early changes after TNF-a antagonist therapy of Achilles enthesitis of AS patients. One hundred AS patients with active disease, requiring TNF-a antagonist therapy, were included (etanercept n = 25, infliximab n = 25, adalimumab n = 25, non-biologic disease-modifying antirheumatic drugs (DMARDs) n = 25). Physical examination was performed to evaluate disease activity and detect Achilles enthesitis and/or retrocalcaneal bursitis. Ultrasound of the Achilles enthesitis was performed bilaterally. Follow-up examinations were performed 3 months after the initiation of therapy. Gray scale (GS) scores, Power Doppler (PD) scores, and total additive scores (TS) decreased significantly during TNF-a antagonist therapy but not in traditional non-biologic traditional DMARDs group. The bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis metrology index (BASMI), bath ankylosing spondylitis functional index (BASFI), and Maastricht ankylosing spondylitis enthesitis score (MASES) all showed significant improvements. When three different TNF-a antagonists were analyzed separately, no significant difference was observed in GS, PD, and total scores. Subclinical Achilles enthesitis, detected only with GS ultrasound, is present in a subset of AS patients and a significant improvement can be demonstrated after 3 months of TNF-a antagonist therapy. Doppler ultrasound provides a reliable estimation to monitor the therapeutic response to TNF antagonists in AS patients with Achilles enthesitis. TNF-a antagonists have been shown to be effective in decreasing ultrasound signs of enthesitis after 3 months of therapy in AS patients.

These findings suggest that in RA patients, abundant CypA up-regulates the calcium-induced chemotactic, adhesive and invasive properties of neutrophils via direct binding to CD147. Cyclophilin-CD147 interactions might contribute to the destruction of cartilage and bone in RA.

IntroductionActivated platelets exert a proinflammatory action that can be largely ascribed to their ability to interact with monocytes. However, the mechanisms that promote dynamic changes in monocyte subsets in rheumatoid arthritis (RA) have not been clearly identified. The aim of this study was to determine whether platelet activation and the consequent formation of monocyte-platelet aggregates (MPA) might induce a proinflammatory phenotype in circulating monocytes in RA.MethodsThe surface phenotype of platelets and the frequencies of monocyte subpopulations in the peripheral blood of RA patients were determined using flow cytometry. Platelets were sorted and co-cultured with monocytes. In addition, monocyte activation was assessed by measuring the nuclear factor kappa B (NF-κB) pathway. The disease activity was evaluated using the 28-joint disease activity score.ResultsPlatelet activation, circulating intermediate monocytes (Mon2) and MPA formation were significantly elevated in RA, especially in those with active disease status. Furthermore, Mon2 monocytes showed higher CD147 expression and responded to direct cell contact with activated platelets with higher cytokine production and matrix metallopeptidase 9 (MMP-9) secretion, which increased the expression of CD147. After the addition of specific antibodies for CD147, those effects were abolished. Furthermore, the NF-κB-driven inflammatory pathway may be involved in this process.ConclusionsThese findings indicate an important role of platelet activation and the consequent formation of MPA in the generation of the proinflammatory cytokine milieu and for the promotion and maintenance of the pathogenically relevant Mon2 monocyte compartment in RA, which is likely to play an important role in the pathogenesis of autoimmunity.

Reliable markers for the rapid discrimination of severe renal damage remain a vital concern for lupus nephritis (LN). To determine a better tool for kidney damage detection, the present study compared the evaluation ability of novel urinary cytokines and chemokines (namely urinary monocyte chemoattractant protein 1 (uMCP-1), tumor necrosis factor-like weak inducer of apoptosis (uTWEAK)) with traditional serum or urinary markers (namely urinary alpha 1-microgrobulin (uα1-MG), beta 2-microglobulin (uβ2-MG) and serum complement C3 (C3), complement C4 (C4), creatinine (Cr), blood urea nitrogen (BUN) and cystatin C (Cys C)) in discriminating LN renal damage. Correlations between markers with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) renal SLEDAI scores, biopsy activity index (BAI) and biopsy chronicity index (BCI) scores were evaluated. Receiver operating characteristic (ROC) curves were generated to evaluate a single or combined model in discriminating active renal involvement (rSLEDAI scores > 0) and patients with poor pathological outcome (BAI scores ≥ 7). uMCP-1 and uTWEAK possess higher correlation coefficients with renal damage and larger areas under ROC curves (AUCs) than other markers. A combined model of uMCP-1 and uTWEAK showed an AUC of 0.887, sensitivity of 86.67% and specificity of 80.00% to discriminate active LN, and an AUC of 0.778, sensitivity of 75.00% and specificity of 81.82% to discriminate LN with poor outcome, which are better than the utility of any markers individually.

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BackgroundThere are more than 5 million RA patients in China, but only 4,000 rheumatologists. T2T strategy are critical for the treatment of RA, but the Chinese doctors can hardly provide patients with a complete assessment in the clinic due to limited time. We have confirmed in a validation study that Chinese RA patients can master the use of SSDM for accurate DAS28 self-assessments after training1.ObjectivesTo explore the effectiveness of applying SSDM in improvement of disease activity after repeated self-assessment in Chinese RA patients.MethodsThe SSDM includes both doctors' and patients' application. After entry of lab test, treatment regiments, and executing DAS28 assessment by patients, all data can be synchronized to the authorized doctor' mobile tool. They can adjust treatment regiments base on these data. Since Aug. 2014 to Jan. 2016, 31 rheumatologists from 25 hospitals participated in the study. Patients were educated to measure DAS28 with SSDM on the baseline, and were asked to repeat the assessment once a month.Results636 RA patients with repeated self-assessment of DAS 28 were recruited, 448 (70.4%) women and 188 (29.6%) men. Mean age was 45.26±13.17 (18 to 83) years, median duration of disease was 2.92 (0.08 to 50.42) years. Mean duration of self-assessment was 67.00±66.50 (2 to 371) days. Mean assessment times were 4.38±3.36 (2–20). Mean DAS28 score was 3.96±1.46 (0.62 to 8.29) at baseline and 3.58±1.45 (0.60 to 9.07) at the last assessment. Proportion of patients in remission, low, moderate and severe disease activity (Rem, LDA, MDA and SDA) was 19.03%, 13.36%, 45.28% and 22.33% respectively at baseline, and changed into 26.57%, 13.68%, 45.28% and 14.47% at the last assessment. The rate of T2T (DAS28≤3.2) at the last assessment was higher than that of baseline significantly (P<0.01). The rate of SDA patients for last assessment was also significantly lower than baseline (P<0.01). To explore whether the frequency of self-assessment could influence disease activity, we stratified the times of DAS28 assessment among those who did not achieve clinical remission (DAS>2.6). 65 patients made only two assessments within 151.41±86.72 (48–372) days, whose mean DAS28 was 4.20±1.28 (2.64–7.39) at baseline and improvement of that was 0.49±1.46 (-4.31–4.25) at their last assessment. There were 61 patients making more than 5 times of self-assessment during 159.98±88.10 (28–343) days. Their mean DAS28 score was 4.27±1.13 (2.61–7.19) at baseline and improvement of that was 1.12±1.34 (-1.86–4.51) at the last assessment, which was significantly better than patients who had only two self-assessments (T=2.52, P=0.013).ConclusionsUnder regular self-assessment of DAS28 using SSDM, RA patients achieved better T2T result. SSDM can assist rheumatologists to rationally adjust treatment for RA patients.ReferencesMu Rong. Feasibility and Influential Factors in Performing Self-Evaluation of DAS28 with SSDM By RA Patient in China. Arthritis Rheumatol. 2015; 67 (suppl 10). Abstract Number: 997Disclosure of InterestNone declared