The ubiquitin-proteasome system is a vital proteolytic pathway required for cell homeostasis. However, the turnover mechanism of the proteasome subunit itself is still not understood. Here, we show that the 20S proteasome subunit PSMA7 is subjected to ubiquitination and proteasomal degradation, which was suppressed by PSMA7 phosphorylation at Y106 mediated by the nonreceptor tyrosine kinases c-Abl/Arg. BRCA1 specifically functions as an E3 ubiquitin ligase of PSMA7 ubiquitination. c-Abl/Arg regulates cellular proteasome abundance by controlling the PSMA7 subunit supply. Downregulated PSMA7 level results in decreased proteasome abundance in c-Abl/Arg RNAi-knockdown or c-abl/arg-deficient cells, which demonstrated an increased sensitivity to proteasome inhibition. In response to oxidative stress, the c-Abl-mediated upregulation of proteasome level compensates for the proteasomal activity impairment induced by reactive oxygen species. Abl-kinases-regulated biogenesis and homeostasis of proteasome complexes may be important for understanding related diseases and pathological states.

BackgroundCurrently, there remains a lack of consensus regarding factors predictive of complication such as re-nonunion after primary revision in femoral shaft nonunion subsequent to failed intramedullary nailing (IMN). A better understanding of prognostic factors could potentially reduce the risk of re-nonunion happening and allow patients to maximize their recovery in the most expeditious manner. Our study aims to identify risk factors in the development of re-nonunion after primary revision inclusive of exchanging reamed nailing (ERN) and augmentative compression plating (ACP) with IMN in situ for femoral shaft nonunion subsequent to failed IMN.MethodsA retrospective study was performed for 63 cases (61 patients) of femoral shaft nonunion subsequent to failed IMN, who were made primary revision with either ERN or ACP from June 2007 to June 2015. The following set of variables was selected based on the speculation that they would contribute to the outcome: sex (male or female), age, body mass index(BMI), smoking, alcohol abuse, cause of injury, fracture type, type of IMN (antegrade or retrograde), use of IMN locking screws(dynamic or static), site of nonunion, primary nonunion time, pathological type of nonunion, bone defect (mm), primary revision method (ERN or ACP), and adjuvant autogenous bone grafting (ABG) (yes or no). Univariate analysis and multiple regression were used to identify risk factors in the development of re-nonunion after primary revision with either ERN or ACP for femoral shaft nonunion subsequent to failed IMN. The minimum follow-up time was 1.5 years (standard deviation [SD] = 1.2, range 1.5–8 years).ResultsOf 63 cases (61 patients) of femoral shaft nonunion subsequent to failed IMN, primary revision with ERN was performed in 33 (52.4%) cases and primary revision with ACP was performed in 30 (47.6%) cases. Adjuvant ABG procedure was undertaken in 39 (61.9%) cases during primary revisions. Re-nonunion was diagnosed as in 18 (28.6%) cases after primary revision with either ERN or ACP. There was a significant difference in time to union between patients treated with primary ERN and those with primary ACP (log-rank, p = 0.006). Furthermore, the difference was also statistically significant between patients with adjuvant ABG procedure and those without it (log-rank, p = 0.009). The relative risk factors included smoking, BMI, site of nonunion, bone defect, primary revision method, and adjuvant ABG procedure. However, primary revision method and adjuvant ABG procedure were shown to be two independent risk factors in multiple logistic regression analysis.ConclusionsPatients with excessive tobacco use, BMI ≥ 30 kg/m2, bone defect ≥ 5 mm, primary revision with ERN, and no adjuvant ABG procedure had a higher likelihood of developing re-nonunion. Of these risk factors, primary revision with ERN and no adjuvant ABG procedure were two strongest risk factors.

The aim of the present study was to compare the efficacy and complications of two fixation techniques, namely dynamic hip screw (DHS) and proximal femoral nail antirotation (PFNA), in the treatment of osteoporotic femoral intertrochanteric fracture in elderly patients, and to detect changes in transforming growth factor β2 (TGF-β2) expression in the two groups. A total of 100 elderly patients with femoral intertrochanteric fracture were randomly divided into two groups that were treated with either DHS or PFNA. Peri-operative complications were observed in the patients and ELISA was used to detect TGF-β2 expression levels at 1, 7, 15 and 30 days after surgical treatment. The clinical efficacy and the incidence rate of complications at 3 months after the operation were compared. In comparison with the DHS group, the PFNA group had a shorter operation time, a lower bleeding volume and a shorter post-operative weight-bearing time. The contents of TGF-β2 in the two groups at 7 days after the operation were higher than those at 1 day, reached a peak at 15 days and had gradually decreased again at 30 days after the operation. The contents of TGF-β2 at 1, 7 and 15 days in the PFNA group were higher than those at the identical time-points in the DHS group (P<0.01). Regarding the clinical efficacy in the two groups at 3 months of post-surgery, the rate of excellent/good efficacy in the PFNA fixation group (90.0%) was higher than that in the DHS fixation group (74.0%). Of note, PFNA fixation had a higher clinical efficacy, a shorter operation time, less intra-operative trauma, a relatively faster fracture healing process and fewer complications in comparison with DHS fixation, and is therefore more suitable for treating osteoporotic femoral intertrochanteric fracture in the elderly. PFNA fixation is superior to DHS fixation, which may be associated with the higher level of TGF-β2 expression in comparison with that in the DHS group.

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