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Aseptic implant loosening is a devastating long-term complication of total joint arthroplasty. It is mainly initiated by the interaction of wear debris and macrophages. However, how does the chronic inflammation persist and how to stop it is poorly understood. Sphingosine kinases (SPHKs) are an essential feature of immunosuppressive M2 polarisation in macrophages and a promoter for chronic inflammation. In this study, RAW 264.7 macrophages were exposed to stimulation with titanium particles (0.1 mg/ml), and the subsequent expression of SPHKs and pro-inflammatory cytokines was evaluated. The effect of inhibitors of SPHKs (FTY720, PF543, and ABC294640) on titanium particle-challenged macrophages was analysed. As for results, the amount of sphingosine kinase (SPHK)-1 and SPHK-2 in RAW264.7 macrophages increased in the presence of titanium particles in a time-dependent manner. Two inhibitors of SPHKs (FTY720 and ABC294640) suppressed titanium particle-induced tumour necrosis factor (TNF)-α and interleukin (IL)-6 production in RAW264.7 macrophages. These findings suggest that persistent stimulation with titanium particles may lead to a consistent release of TNF-α and IL-6 via SPHK-2 activity, which may lead to aseptic implant loosening. Appropriate regulation of SPHK-2 may serve as a potential new strategy in the treatment of aseptic implant loosening. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to evaluate the isolated benefits of patellar non-eversion in total knee arthroplasty (TKA).Methods: This systematic review and meta-analysis was conducted following the PRISMA statement. A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and Embase databases was performed in August 2014. Randomized controlled trials (RCTs) that considered the handling of the patella as the only variable were included in our review. Quality assessment of RCTs was performed according to the CONSORT statement. The meta-analysis was performed to pool the available data for some parameters.Results: The searches of the MEDLINE/PubMed, Cochrane Library, and Embase databases yielded 10 RCTs, and five RCTs were selected for inclusion in the review. This results suggested that tourniquet time [mean difference (MD) = -5.69; 95% confidence interval (CI) -9.77 to -1.60], length of hospitalization (MD = 1.24; 95% CI 0.54-1.94) and the incidence of complications [odds ratio (OR) = 2.23; 95% CI 1.12-4.44] differed significantly between the eversion group and non-eversion group. No differences in postoperative pain, alignment, and the Insall-Salvati ratio were observed between the groups.Conclusion: The patellar non-eversion approach offers a shorter length of hospitalization and lower incidence of postoperative complications, but requires more operative time. The merits of patellar non-eversion for recovery of knee function remain controversial, and more high-quality RCTs are needed to draw clear conclusions. In general, avoidance of patellar eversion is recommended when exposing the knee joint for TKA. [ABSTRACT FROM AUTHOR]