gelatinase expressed in three major forms: dimer, monomer and a complex with neutrophil gelatin-associated lipocalin (NGAL). Interleukin-(IL)-6 is a pleiotropic cytokine expressed by a variety of immune and non-immune cells. However, the mechanisms by which IL-6 contributes to the pathogenesis of chronic arthropathies are not fully understood. Objectives: The purpose of the present work was to perform a comparative study of the IL-6 production and MMP-9 activity in FLS stimulated with SF from patients with osteoarthritis (OA), rheumatoid arthritis (RA) or spondyloarthritis (SpA). In addition, the effect of IL-6 blockade on MMP-9 activity was evaluated. Methods: Primary FLS were obtained from SF of the RA patients. Furthermore, the SW982 human synovial cell line was used. The SF of patients with OA (n=11), RA (n=11) or SpA (n=9) patients were pooled. The FLS were stimulated with OA, RA or SpA SF pools and supernatants (SN) were collected after 24, 48 and 72 h. The IL-6 levels were assessed in the SN by ELISA. The gelatinase activity of the SN was determined by zymography. The IL-6 function was blocked with the anti-IL-6 receptor antagonist tocilizumab (TCZ) (200μg/ml). Results: Earlier induction of IL-6 in SW982 cell line was observed by RA and SpA SF stimulation since significant levels were detected at 24 h (p<0.001 and p<0.01 compared with non-stimulated cells, respectively), whilst OA SF induced significant IL-6 secretion at 72 h (p<0.01). Similar results were observed in primary FLS. In contrast to SF of OA patients, SF of patients with RA or SpA induced increased and sustained secretion of active MMP-9. Moreover, the molecular weight band corresponding with NGAL-MMP-9 complex, considered a protected form of MMP-9, was detected with higher intensity in the SN of FLS stimulated with RA or SpA SF compared with OA SF (p<0.001). In the presence of TCZ, significant inhibition in the gelatinase activity of all MMP-9 forms was observed at 48h of stimulation with RA or SpA SF (p<0.001 for MMP-9 dimer and NGAL-MMP-9 complex; p<0.01 for MMP-9 monomer, compared with FLS stimulated in absence of TCZ). Conclusions: We conclude that SF of patients with inflammatory arthritis recreate a differential microenvironment for FLS that impacts on early phenotypic changes of these cells. The IL-6 provokes augmented and persistent MMP-9 activity in FLS stimulated with RA or SpA SF. This work identifies TCZ as an inhibitor of all forms of MMP-9.

Background Intermittent exotropia (IXT) would cause different degrees of damage to stereopsis. We aimed to introduce a visual perception plasticity score (VPPS) that reflects initial postoperative plasticity and evaluate its effectiveness in predicting the mid-term surgical outcome in IXT patients. Methods A total of 149 patients with intermittent exotropia who underwent surgery in November 2018 and October 2019 were recruited. All subjects underwent detailed ocular examinations before and after surgery. VPPS were calculated based on visual perception examination system at one week postoperatively. Demographic, angle of deviation and stereopsis were collected and analyzed with regard to the VPPSs preoperatively and at one week, one month, three months, six months postoperatively. Predictive performances of VPPS were assessed using receiver operating characteristic (ROC) curves, the area under the curve (AUC) and cut-offs were obtained. Results Of the 149 patients, the average deviation was 43Δ at distance and 46Δ at near. The average rate of normal stereopsis before surgery was 22.81% at distance and 29.53% at near. Higher VPPS was associated with preoperative better near stereoacuity (r = 0.362, p = 0.000), less angle of deviation at distance (r=-0.164, p = 0.046), and better near (r = 0.400, p = 0.000) and distant stereoacuity (r = 0.321, p = 0.000) during the early postoperative period (1 week). The areas under the curves suggested that VPPS could be an effective predictor of sensory outcome(AUC>0.6). Cut-off values of 50 and 80 were calculated for VPPS using ROC curve analysis. Conclusion Higher VPPSs were associated with a greater possibility of stereopsis improvement in patients with IXT. VPPS is a potentially promising indicator to predict the mid-term surgical outcome of intermittent exotropia.

BackgroundmTOR signaling is proved to be one of the most important pathway in the pathogenesis in SLE. However, in patients with SLE, whether mTOR pathway can be activated by low-dose IL-2 remained unclear.ObjectivesTo clarify the effects of low-dose IL-2 therapy on mTOR signaling in the treatment of SLE.MethodsEight patients with active SLE were treated with 1 million IU IL-2. Phophrylation of S6 ribosomal protein (S6RP), AKT and pSTAT5 were measured before and after the first 2 week of low-dose rhIL-2 administration. C57BL/6 mice (male, 8–12 weeks old) were intraperitoneally immunized with SRB and followed by administration of different doses (low:10,000 IU and hight:300,000 IU) of rhIL-2 or PBS from day 3 to day 9. The ratio of Th1, Th2, Tfh, Th17, Tfh and Treg as well as the level of S6RP, AKT and pSTAT5 were assayed by flow cytometryResultsLow-dose IL-2 was efficient and well tolerated in active SLE, and was associated with expansion of Treg cells (p<0.001) and reductions of Tfh and Th17 cells (p≤0.001). No significant change of pS6RP and pAKT was observed. On the other hand, there was a signfciant induction of the activation of STAT5. In mouse studies, low-dose IL-2 inhibited the differentiation of Th17 cells and Tfh cells. Comparing with high dose IL-2 group, there was no significantly increased mTOR activity after low-dose IL-2 administration.ConclusionsLow-dose IL-2 might circumvent mTOR pathway and play a regulatory role in the T cells in lupusDisclosure of InterestNone declared