Rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) show resistance to methotrexate (MTX) treatment. To better understand the mechanisms of this resistance, RA-FLS and osteoarthritis fibroblast-like synovial cells (OA-FLS) were isolated and exposed to MTX. We analyzed the autophagy induced by MTX in vitro and its relationship to apoptosis. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and apoptosis was detected by flow cytometry and Western blot analysis. Autophagy was determined by transmission electron microscopy as well as Western blot analysis. The expression levels of Beclin-1, LC3, Akt, p-Akt, mammalian target of rapamycin (mTOR), p-mTOR, high mobility group box chromosomal protein 1 (HMGB1), and an 85 kDa caspase cleaved fragment of poly(ADP-ribose) polymerase were measured by Western blotting. MTX-induced apoptosis was increased in OA-FLS compared with RA-FLS. However, MTX stimulated the autophagy response in RA-FLS by inducing autophagosome formation, but not in OA-FLS. In RA-FLS, transfection with Beclin-1 small interfering RNA inhibited autophagy and increased susceptibility to MTX, which induces cell death. MTX upregulated autophagy through its ability to enhance the expression of HMGB1 and Beclin-1 rather than through the Akt/mTOR pathway. Autophagy induction contributes to resistance to MTX treatment in fibroblasts from patients with rheumatoid arthritis.

Twenty percent of ankle fractures present with concomitant syndesmosis injury which results in poor clinical outcomes. Surgical stabilization of the syndesmosis can be achieved with either trans-syndesmotic screws or a suture-button device. The aim of this study is to investigate the clinical efficacy of suture-button fixation and trans-syndesmotic screw fixation in the treatment of ankle fracture combined with distal tibiofibular syndesmosis injury. A retrospective analysis was conducted by enrolling 76 patients with ankle fractures combined with distal tibiofibular syndesmosis injury who were admitted in our trauma center from January 2018 to January 2019, including 34 cases of suture button group and 42 cases of the syndesmotic screw group with a mean follow-up period of 16 ± 7 (range 12 to 21) months. The demographic data included gender, age, injury mechanism, AO classification and the operation duration were recorded, the radiographic and clinical outcomes were determined by tibiofibular clear space, tibiofibular overlap distance, complications, and the Olerud-Molander Ankle Score at the last follow-up. All the indexes were compared between the two groups to discover the related statistical differences. With the numbers available, no significant difference could be detected in the surgical duration, tibiofibular clear space, tibiofibular overlap distance, total complication rate, and middle-term Olerud-Molander Ankle scores between the two groups. However, the suture button fixation group showed higher early stage Olerud-Molander Ankle scores(p=.027) and shorter full weightbearing time(p=.018) than that of syndesmotic screw fixation group. Considering the outcomes, we conclude that the suture-button fixation not only shows equivalent efficacy to the traditional syndesmotic screw, but also has advantages of allowing early weight bearing, low requirements for routine removal.

P62 (also known as sequestosome 1) protein, is a small regulatory protein that accumulates in autophagy‑defective cells that has been demonstrated to be involved in the prognosis and survival of patients with several types of cancer. However, to the best of our knowledge, there have been no such studies for osteosarcoma (OS). In the present study, the expression of p62 in 70 OS samples was determined using immunohistochemistry and its association with various clinicopathological factors was assessed. The results demonstrated that the overexpression of p62 protein was detected in 77.1% (54/70) samples, and the expression levels were significantly associated with tumor size (P=0.001), metastasis (P=0.036), clinical staging (P=0.003) and poor prognosis (P=0.0058). Furthermore, suppression of the p62 expression by short hairpin RNA interference in F5M2 and F4 cells lines led to decreased cell proliferation, migration and invasion in vitro. These results suggested that increased expression of p62 may be involved in OS progression, and therefore the excess expression of p62 may serve as a novel prognostic biomarker for patients with OS.

The surgical approaches remain controversial for the treatment of middle and distal-third humeral shaft (MDTHS) fractures. This study compared clinical effects of the anterolateral approach with two incisions (AATI) and the posterior median approach (PMA) in the treatment of MDTHS fractures. A retrospective analysis was carried out. One hundred sixty-six patients with MDTHS fractures were selected from January 2015 to January 2017 in Xi’an Hong Hui Hospital. According to surgical approaches, patients were divided into AATI (86 cases) and PMA group (80 cases). All patients were treated with open reduction and plate fixation. Operation indexes were compared, including incision length, operation time, and bleeding. Bryan-Morrey score was used to evaluate elbow joint function. Complication incidence was compared, such as incision infection, iatrogenic radial nerve injury, and nonunion. The AATI group showed smaller incision length, less bleeding, lower iatrogenic radial nerve injury rate, and better elbow function than that of PMA group (P<0.05). The middle and distal-third humeral shaft fractures can be successfully cured by both approaches. Compared with the posterior median approach, it has better clinical effects of the anterolateral approach with two incisions, which is worthy of clinical application and promotion.