MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1.

Background Fibroblast-like synoviocytes (FLSs) that line the intimal synovium play a crucial role in the pathogenesis of rheumatoid arthritis (RA). miR-199a-3p is a highly conserved miRNA that has been shown to regulate a variety of growth behaviors in diverse cell types. However, the role of miR-199a-3p in RA-FLS is still unknown. Methods Here, we presented the first experimental evidence showing that miR-199a-3p was a critical regulator of RA-FLS function. Results miR-199a-3p expression was significantly reduced in RA-FLS compared with normal FLS. Ectopic expression of miR-199a-3p significantly inhibited RA-FLS proliferation and induced apoptosis, which was demonstrated by an increase in caspase-3 activity and Bax/Bcl-2 ratio. Our bioinformatics analysis identified Retinoblastoma 1 (RB1) gene to be a direct target of miR-199a-3p. In RA-FLS, miR-199a-3p directly targetted the 3'-UTR of RB1 mRNA and suppressed endogenous RB1 expression, whereas miR-199a-3p-resistant variant of RB1 was not affected. Silencing RB1 decreased cell proliferation and promoted apoptosis in RA-FLS, an effect comparable with miR-199a-3p overexpression. Enforced expression of RB1 partially restored cell proliferation and attenuated apoptosis in miR-199a-3p-overexpressing RA-FLSs. Conclusion In summary, miR-199a-3p is down-regulated in RA-FLS, and miR-199a-3p inhibits proliferation and induces apoptosis in RA-FLS, partially via targetting RB1. The miR-199a-3p/RB1 pathway may represent a new therapeutic target for RA.

Upregulation of P63 inhibits chondrocyte autophagy thereby enhancing the malignant progression of osteoarthritis.

Loss of autophagy is suggested to play a key role in the progression of osteoarthritis (OA). P63 is a member of the P53 family, which is widely dysregulated in various tumors. However, the specific role of P63 in chondrocyte autophagy has never been fully understood. Here, the expression level of P63 in the articular cartilages of OA patients and chondrocytes treated with 3-MA was explored using western blot. Autophagy was determined using transmission electron microscopy and mRFP-GFP-LC3 assay. Fewer autophagic vesicles were identified in the articular cartilages of OA patients compared with that of normal control. Both the mRNA and protein levels of P63 was markedly increased in the articular cartilages of OA patients compared with that of normal control. MTT assay demonstrated that P63 overexpression markedly reduced chondrocyte viability at 24, 36 and 48 h, while inhibition of P63 inhibited cell viability at 24, 36 and 48 h, respectively. Furthermore, autophagic flux assay showed that transfection of ad-P63 markedly decreased the yellow dots in chondrocytes, while inhibition of P63 induced chondrycyte autophagy. In summary, we first demonstrated that upregulation of P63 in the cartilage tissues of OA patients inhibited chondrocyte autophagy thereby contributing to the malignant progression of OA.

Effect of Chemical Thromboprophylaxis on the Rate of Venous Thromboembolism After Treatment of Foot and Ankle Fractures.

BACKGROUND: Venous thromboembolism (VTE) is a well-documented complication in patients with lower limb fractures, but management guidelines for its prevention in isolated foot and ankle fracture patients are conflicting. The aim of this study was to conduct a multicenter, prospective cohort study to define the prevalence of VTE in patients with isolated foot and ankle fractures and determine whether routine prophylaxis is necessary in these patients. METHODS: In a double-blind, placebo-controlled study, consecutive patients in 3 hospitals who met our criteria were enrolled. After randomization, patients received either thromboprophylaxis with low-molecular-weight heparin units (LMWH group) or placebo (placebo group) for a period of 2 weeks. All patients underwent routine ultrasonography 1 day preoperatively, 1 week postoperatively, and 1 month postoperatively. Demographic parameters were then collected and compared. RESULTS: Of the 814 patients who met our criteria, 19 patients (2.3%, 95% confidence interval [CI], 0%-31.9%) were found to have objectively confirmed VTE, but none of the patients were symptomatic. Of the 411 patients in the LMWH group, 2 developed VTEs preoperatively and 4 postoperatively; of the 403 patients in the placebo group, 5 developed VTEs preoperatively and 8 postoperatively. The overall incidence of asymptomatic postoperative deep vein thrombosis (DVT) was 0.98% (95% CI 0%-20.3%) in the LMWH group and 2.01% (95% CI 0%-29.5%) in the placebo group without significant difference. Advanced age (odds ratio [OR] 1.050, 95% CI 1.014-1.088, P = .007) and high body mass index (OR 1.201, 95% CI 1.034-1.395, P = .016) were identified as risk factors in predicting occurrence of DVT. No fatal pulmonary emboli or major bleeding complication occurred in either group. CONCLUSION: Routine anticoagulant prophylaxis was not found to be necessary for patients with foot and ankle fractures, although further investigation with a properly powered study design is required to definitively determine which foot and ankle patients are best served by anticoagulation and which ones are not. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Anatomical study of simple landmarks for guiding the quick access to humeral circumflex arteries.

BACKGROUND: The posterior and anterior circumflex humeral artery (PCHA and ACHA) are crucial for the blood supply of humeral head. We aimed to identify simple landmarks for guiding the quick access to PCHA and ACHA, which might help to protect the arteries during the surgical management of proximal humeral fractures. METHODS: Twenty fresh cadavers were dissected to measure the distances from the origins of PCHA and ACHA to the landmarks (the acromion, the coracoid, the infraglenoid tubercle, the midclavicular line) using Vernier calipers. RESULTS: The mean distances from the origin of PCHA to the infraglenoid tubercle, the coracoid, the acromion and the midclavicular line were 27.7 mm, 50.2 mm, 68.4 mm and 75.8 mm. The mean distances from the origin of ACHA to the above landmarks were 26.9 mm, 49.2 mm, 67.0 mm and 74.9 mm. CONCLUSION: Our study provided a practical method for the intraoperative identification as well as quick access of PCHA and ACHA based on a series of anatomical measurements.

Will the untreated ulnar styloid fracture influence the outcome of unstable distal radial fracture treated with external fixation when the distal radioulnar joint is stable.

BACKGROUND: The ulnar styloid is an important supportive structure for the triangular fibrocartilage complex. However, it remains inconclusive whether or not a fractured ulnar styloid should be fixed in an unstable distal radius fracture (DRF) with a stable distal radioulnar joint (DRUJ). The purpose of this study is to evaluate the effect of an untreated ulnar styloid fracture on the outcome of unstable DRF treated with transarticular external fixation when the DRUJ is stable. METHODS: 106 patients with an unstable DRF and a stable DRUJ were included in this study following external fixation. The patients were divided into the non-fracture, the tip-fracture and the base-fracture groups according to the location of the ulnar styloid fracture at the time of injury. Postoperative evaluation included the range of wrist motion, the radiological index, the grip strength, the PRWE-HK scores, the wrist pain scores, and the instability of DRUJ at the external fixator removal time, three months postoperatively and the final follow-up visit. RESULTS: The patients were followed for 12 to 24 months (15 months in average). Sixty-two of 106 patients (58%) had ulnar styloid fracture and 16 patients (26%) showed radiographic evidence of union of ulnar styloid fractures at the final follow-up visit. No significant difference in the radiological findings, the range of wrist motion, the grip strength, the PRWE-HK scores, and the wrist pain scores among three patient groups was detected at the external fixator removal time, three months postoperatively, or the final follow-up visit. Six of the 106 patients (5.7%) complained of persistent ulnar-side wrist pain during daily activities. One patient (0.9%) showed a positive sign in a stress-test, three patients (2.8%) showed a positive sign in a provocative-test, and five patients (4.7%) showed a positive sign in a press-test. There was no significant difference in the percentages of patients who complained of persistent ulnar-side wrist pain or showed a positive sign in the physical examination of the distal radioulnar joint among the three groups at the final follow-up time points. CONCLUSION: When the DRUJ is stable, an untreated ulnar styloid fracture does not affect the wrist outcome of the patient with an unstable DRF treated with external fixation.