A Comparative Study of the Early Postoperative Outcome of Three Intramedullary Fixation Modalities in the Treatment of Intertrochanteric Fractures of the Femur in the Elderly.

OBJECTIVES: To compare early outcomes of proximal femoral bionic nail (PFBN), Inter-TAN, proximal femoral nail antirotation (PFNA) for intertrochanteric fractures in elderly patients. METHODS: Eighty-two elderly patients with intertrochanteric femoral fractures treated at Xiangyang No. 1 People's Hospital affiliated with Hubei University of Medicine from December 2021 to 2022 were retrospectively analyzed. They were categorized into three surgical groups: PFBN (22 cases), Inter-TAN (20 cases), and PFNA (40 cases). Preoperative demographics and fracture characteristics were compared, alongside intraoperative and postoperative metrics like operative time and complication rates. RESULTS: In the PFBN group, operative time, fluoroscopy use, blood loss, and transfusion were higher, but postoperative weight-bearing, healing, and hospital stay were shorter compared to the Inter-TAN and PFNA groups (P<0.05). Inter-TAN had a significantly shorter postoperative weight-bearing time than PFNA (P<0.001). Other compared factors showed no significant differences between groups (P>0.05), including complication rates and scores at 6-month follow-up. CONCLUSIONS: PFBN, a novel surgical approach for intertrochanteric fractures in elderly patients, outperforms Inter-TAN and PFNA by accelerating early weight-bearing and hastening fracture recovery.

MAPK-interacting kinases inhibition by eFT508 overcomes chemoresistance in preclinical model of osteosarcoma.

The MAPK-interacting kinases 1 and 2 (MNK1/2) have generated increasing interest as therapeutic targets for many cancers with little known in osteosarcoma. This study evaluated the efficacy of eFT508, a highly selective inhibitor of MNK1/2, as single drug alone and in combination with paclitaxel in preclinical models of osteosarcoma. EFT508 is active against multiple osteosarcoma cell lines via inhibiting growth, survival and migration. It also demonstrates anti-osteosarcoma selectivity with much less toxicity on normal osteoblastic than osteosarcoma cells. Consistent with in vitro findings, eFT508 at non-toxic dose significantly arrested tumor growth in mice throughout the whole duration of treatment. Mechanistically, eEFT508 is highly effective in blocking eIF4E phosphorylation and eIF4E-mediated protein translation. Combination index shows that eFT508 and paclitaxel is synergistic in osteosarcoma cells. Our findings highlight the therapeutic value of MNK1/2 inhibition and suggest eFT508 as a promising candidate for the treatment of osteosarcoma.

KR­12­a6 promotes the osteogenic differentiation of human bone marrow mesenchymal stem cells via BMP/SMAD signaling.

Considering the increased resistance to antibiotics in the clinic and the ideal antibacterial properties of KR­12, the effects of KR­12­a6, an important analogue of KR­12, on the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) were investigated. Osteogenic differentiation­associated experiments were conducted in hBMSCs, and KR­12­a6 was used as an additional stimulating factor during osteogenic induction. Quantitative analysis of alkaline phosphatase (ALP) and alizarin red staining, and reverse transcription­quantitative PCR analysis of the expression of osteogenesis­associated genes were performed to determine the effects of KR­12­a6 on the osteogenic differentiation of hBMSCs. LDN­212854 was selected to selectively suppress BMP/SMAD signaling. Western blotting was performed to investigate the underlying mechanisms. The intensity of ALP and alizarin red staining gradually increased with increasing KR­12­a6 concentrations. KR­12­a6 induced the strongest staining at 40 µg/ml, whereas 60 µg/ml and 80 µg/ml concentrations did not further increase the intensity of staining. The mRNA expression levels of RUNX2 and ALP increased in a dose­dependent manner as early as 3 days post­KR­12­a6 treatment. The mRNA expression of COL1A1, BSP and BMP2 exhibited significant upregulation from day 7 post­KR­12­a6 treatment. In contrast, the mRNA levels of OSX, OCN and OPN were enhanced dramatically at day 14 following KR­12­a6 stimulation. Additionally, KR­12­a6 significantly promoted the phosphorylation of Smad1/5. Furthermore, LDN­212854 suppressed the activation of Smad1/5 and inhibited the upregulation of several osteogenic differentiation­associated genes in KR­12­a6­treated hBMSCs. KR­12­a6 promoted the osteogenic differentiation of hBMSCs via BMP/SMAD signaling.