Circ_0002984 promotes proliferation, migration and inflammatory cytokine secretion and inhibits apoptosis of rheumatoid arthritis fibroblast-like synoviocytes by inducing PCSK6 through miR-543.

BACKGROUND: Rheumatoid arthritis (RA) is inflammatory arthritic disease, and circular RNA is involved in RA development. The aim of the present work is to analyze the role of circ_0002984 in the process of RA fibroblast-like synoviocytes (RAFLSs) and the underlying mechanism. METHODS: Circ_0002984, miR-543, and proprotein convertase subtilisin/kexin type 6 (PCSK6) expression levels were analyzed by quantitative real-time polymerase chain reaction or western blotting. Cell proliferation, migration, inflammatory response, and apoptosis were investigated through 5-Ethynyl-2'-deoxyuridine assay, wound-healing assay, enzyme-linked immunosorbent assay, and flow cytometry analysis. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to assess the binding relationship. RESULTS: Circ_0002984 and PCSK6 expression were increased, while miR-543 expression was decreased in the synovial tissues of RA patients and RAFLSs. Circ_0002984 introduction facilitated RAFLS cell proliferation, migration and inflammatory response and repressed apoptosis, but circ_0002984 knockdown had an opposite role. Circ_0002984 targeted miR-543, and PCSK6 was targeted by miR-543. MiR-543 downregulation or PCSK6 overexpression restored the effects of circ_0002984 interference on RAFLS phenotypes. CONCLUSION: Circ_0002984 promoted RAFLS proliferation, migration and inflammatory cytokine secretion and inhibited apoptosis by binding to miR-543 to induce PCSK6 production, providing a potential target for RA therapy.

Incidence and Predictive Factors of Tibial Fracture with Occult Posterior Ankle Fractures.

Background: Few studies exist on the predictive factors of tibial fractures with hidden posterior ankle fractures. Objective: To study the incidence and predictive factors of tibial fractures with occult posterior ankle fractures. Methods: Tibial fracture patients were prospectively selected who were admitted to our hospital from January 2016 to May 2021 and their general clinical data, X-ray images, CT images, and other imaging data were collected and then divided them into posterior malleolus fracture group and nonposterior malleolus fracture group according to the presence or absence of posterior malleolus fractures. Multivariate regression analysis and receiver operating curves (ROC) were performed to analyze the influencing factors of tibial fracture with occult posterior ankle fracture. Results: CT showed that 25 (13.44%) patients had occult posterior ankle fractures among 186 patients with tibial fracture. There was no significant difference in gender, age, and locations of tibial fracture between the two groups (P > 0.05). There were statistical differences in the types, locations, and lengths of patients with tibial fracture but without posterior malleolus fractures. The length of the tibia fracture group was significantly lower than the tibia with posterior ankle fracture group (P < 0.05). Logistics regression analysis showed that tibial fracture with occult posterior ankle fracture was not significantly correlated with gender, age, and location of tibial fracture (P > 0.05), but was significantly correlated with tibial fracture type, location, and length (HR = 1.830, P=0.035; HR = 5.161, P=0.004; HR = 1.126, P=0.030). The ROC curve showed that the AUC of length of tibial fracture with occult posterior ankle fracture was 0.599. The YD index suggested that the best cut point for the prediction of tibial fracture with occult posterior ankle fracture was above 13.18%. The sensitivity and specificity of spiral tibial fracture and distal 1/3 tibial fracture for prediction were 88.00% and 63.35%, 92.00%, and 58.39%, respectively, which was significantly higher than that of tibial fracture length (P < 0.05). Conclusion: Patients with tibial fractures have a higher incidence of occult posterior ankle fractures. Spiral tibial fractures and distal 1/3 tibial fractures have a higher predictive value for tibial fracture with occult posterior ankle fractures and can help clinical detection as soon as possible, which is a more accurate and appropriate treatment.