ITGB3 promotes cisplatin resistance in osteosarcoma tumors.

OBJECTIVE: Osteosarcoma is the most malignant and common primary bone tumor with a high rate of recurrence that mainly occurs in children and young adults. Therefore, it is vital to facilitate the development of novel effective therapeutic means and improve the overall prognosis of osteosarcoma patients via a deeper understanding of the mechanisms of chemoresistance in osteosarcoma progression. METHODS: In this research, the relationship between ITGB3 and the clinical characteristics of patients was detected through analysis of publicly available clinical datasets. The expression of ITGB3 was analysis in collected human osteosarcoma tissues. In addition, the potential functions of ITGB3 in the cisplatin resistance of osteosarcoma cells were investigated in vitro and in tumor xenotransplantation. Finally, the molecular mechanism of ITGB3 in the progression and recurrence of osteosarcoma were explored via transcriptome analysis. RESULTS: ITGB3 was identified as a potential regulator of tumorigenicity and cisplatin resistance in relapsed osteosarcoma. Furthermore, the decreased osteosarcoma cell proliferation and migration ability in ITGB3 knockout osteosarcoma cells were related to increased apoptosis and slowing cell cycle progression. In addition, ITGB3 had a positive correlation with cisplatin resistance in cells and tumor xenografts in mice. Accordingly, ITGB3 performed the functions of proliferation and cisplatin resistance in osteosarcoma through the MAPK and VEGF signaling pathways. CONCLUSION: Our results will contribute to a better understanding of the function and mechanism of ITGB3 in osteosarcoma cisplatin resistance and provide a novel therapeutic target to decrease cisplatin resistance and tumor recurrence in osteosarcoma patients.

Risk factors for postoperative medical morbidity and 3-month mortality in elderly patients with hip fracture following hip arthroplasty during COVID-19 pandemic.

BACKGROUND: The purpose of the current study was to investigate the incidence of postoperative medical complications and 3-month mortality in patients ≥ 70 years old with hip fracture following hip arthroplasty (HA) and independent risk factors associated with postoperative medical complications and 3-month mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. METHODS: A multicenter retrospective study was conducted, patients ≥ 70 years old with HA for hip fracture under general anesthesia were included during COVID-19 and before COVID-19 pandemic. The outcome was defined as postoperative medical complications and 3-month mortality. The baseline characteristics and risk factors were collected, multivariable logistic regression was used to identify independent risk factors for postoperative medical complications and 3-month mortality. RESULTS: A total of 1096 patients were included during COVID-19 pandemic and 1149 were included before COVID-19 pandemic in the study. Patients ≥ 70 years with hip fracture for HA had longer fracture to operation duration (7.10 ± 3.52 vs. 5.31 ± 1.29, P < 0.001), and the incidence of postoperative medical complications (21.90% vs. 12.53%, P < 0.001) and 3-month mortality (5.20% vs. 3.22%, P = 0.025) was higher during COVID-2019 pandemic. Multivariate logistic regression analysis showed that dementia (OR 2.73; 95% CI 1.37-5.44; P = 0.004), chronic obstructive pulmonary disease (COPD) (OR 3.00; 95% CI 1.92-4.71; P < 0.001), longer fracture to operation duration (OR 1.24; 95% CI 1.19-1.30; P < 0.001) were associated with increased risk for postoperative medical complications. COPD (OR 2.10; 95% CI 1.05-4.17; P = 0.035), dementia (OR 3.00; 95% CI 1.11-7.94; P = 0.031), postoperative medical complications (OR 4.99; 95% CI 2.68-9.28; P < 0.001), longer fracture to operation duration (OR 1.11; 95% CI 1.04-1.19; P = 0.002) were associated with increased risk for 3-month mortality. CONCLUSIONS: In conclusion, we found that postoperative medical morbidity and 3-month mortality in patients with hip fracture underwent HA were 21.90% and 5.20%, respectively, during the COVID-19. COPD, dementia and longer fracture to operation duration were associated with negative outcome in patients with hip fracture underwent HA during the COVID-19.

The Long Noncoding RNA ZEB2-AS1 Contributes to Proliferation and Epithelial-to-Mesenchymal Transition of Osteosarcoma.

Background: Long non-coding RNA Zinc finger E-box binding homeobox 2 (ZEB2) antisense RNA 1 (ZEB2-AS1) has been shown to promote tumor progression. However, the clinical significance and fundamental function role of ZEB2-AS1 in osteosarcoma (OS) has been poorly understood. Methods: The expression of ZEB2-AS1 was determined in tumor tissues and matched normal tissues from 67 OS patients using quantitative reverse transcriptase PCR analysis. Clinical value of ZEB2-AS1 was evaluated by χ2 test and Kaplan-Meier method. Cell proliferation was analyzed using CCK-8 assay, colony formation. Cell apoptosis status was determined by caspase-3 activity assay. Cell migration, invasion and epithelial-mesenchymal transition (EMT) were investigated by scratch wound healing, transwell invasion assays and Western blotting. Results: Clinical association analysis revealed that high ZEB2-AS1 expression correlated with tumor size, distant metastasis and poor prognosis of OS patients. Moreover, ZEB2-AS1 expression was identified as an independent prognostic factor for OS patients. Loss-of-function assays demonstrated that ZEB2-AS1 knockdown suppressed the proliferation and induced apoptosis in OS cells. In addition, ZEB2-AS1 knockdown inhibited cell migration, invasion, EMT of OS cells in vitro. Conclusions: Taken together, our data demonstrate that ZEB2-AS1 serves a putative oncogenic role and associates with unfavorable prognosis in OS.

Exosomes: A promising therapeutic strategy for intervertebral disc degeneration.

As a common problem all over the world, low back pain (LBP) places a huge social and economic burden on people. Intervertebral disc degeneration (IDD) is often considered to be the main cause of low back pain. The current methods of treating disc degenerative diseases mainly focus on relieving symptoms, including surgery and conservative treatment, but none of them can be treated with the etiology, which means that the normal structure of the intervertebral disc cannot be fundamentally restored. With the development of tissue engineering and regenerative medicine, exosomes from different sources, especially mesenchymal stem cell-derived exosomes (MSC-exos) as active biological substances for intercellular communication have made rapid progress due to their potency in promoting tissue regeneration. The study of exosomes in the field of treatment of IDD has yielded many surprising results. This paper mainly reviews the mechanism and function of exosomes in the study of delaying or reversing IDD, as well as gives the prospects and challenges of exosomes.

Analysis of risk factors for 90-day mortality after surgery in elderly patients with intertrochanteric fractures and a history of cardiovascular disease.

BACKGROUND: This study explored the risk factors for all-cause mortality 90 days after surgery in elderly patients with intertrochanteric fractures and a history of cardiovascular disease. METHODS: We retrospectively analyzed the clinical data of 166 elderly patients with intertrochanteric fractures who were admitted to the Department of Orthopedics of Sichuan Provincial People's Hospital (Eastern Hospital) between January 1, 2010 and December 31, 2014. Kaplan-Meier survival curve analysis and the logrank test were used to compare all-cause mortality in the 90-day postoperative period for elderly patients with intertrochanteric fractures and a history of cardiovascular disease. In addition, we used the Cox proportional hazards model to explore related risk factors and their relative hazard rate (HR). RESULTS: A multivariate Cox regression model was established for elderly patients with intertrochanteric fractures and a history of cardiovascular disease and all-cause mortality within 90 days after surgery. The risk factors suggested by the model were length of hospital stay (HR =1.07, Z=4.26, P<0.001), N-terminal pro brain natriuretic peptide (NT-proBNP) (HR =1.01, Z=4.61, P<0.001), and high-density lipoprotein (HDL) (HR =0.41, Z=2.05, P=0.042). The area under the working curve (AUC) of the Cox regression model was 0.91. The Kaplan-Meier survival curves grouped by length of stay, NT-proBNP, and HDL risk factors were significantly different (P<0.05). CONCLUSIONS: As the length of hospital stay increased, abnormally elevated NT-proBNP significantly increased all-cause mortality within 90 days after surgery, while elevated HDL significantly reduced patient mortality. The results of our study suggested that the combination of these 3 indicators could be used as a sensitive predictor for prognosis in elderly patients with intertrochanteric fracture surgery and a history of cardiovascular disease.

[Clinical application of atlas translaminar screws fixation in treatment of atlatoaxial instability].

OBJECTIVE: To explore the effectiveness of fixation of atlas translaminar screws in the treatment of atlatoaxial instability. METHODS: A retrospective analysis was made on the clinical data of 32 patients with atlatoaxial instability treated with atlantoaxial trans-pedicle screws between March 2007 and August 2009. Of them, 7 patients underwent atlas translaminar screws combined with axis transpedicle screws fixation because of fracture types, anatomic variation, and intraoperative reason, including 5 males and 2 females with an average age of 48.2 years (range, 35-69 years). A total of 9 translaminar screws were inserted. Injury was caused by traffic accident in 4 cases, falling from height in 2 cases, and crushing in 1 case. Two cases had simple odontoid fracture (Anderson type II), and 5 cases had odontoid fracture combined with other injuries (massa lateralis atlantis fracture in 2, atlantoaxial dislocation in 1, and Hangman fracture in 2). The interval between injury and operation was 4-9 days (mean, 6 days). The preoperative Japanese Orthopaedic Association (JOA) score was 8.29 +/- 1.60. RESULTS: The X-ray films showed good position of the screws. Healing of incision by first intention was obtained, and no patient had injuries of the spinal cord injury, nerve root, and vertebral artery. Seven cases were followed up 9-26 months (mean, 14 months). Good bone fusion was observed at 8 months on average (range, 6-11 months). No loosening, displacement, and breakage of internal fixation, re-dislocation and instability of atlantoaxial joint, or penetrating of pedicle screw into the spinal canal and the spinal cord occurred. The JOA score was significantly improved to 15.29 +/- 1.38 at 6 months after operation (t = 32.078, P = 0.000). CONCLUSION: Atlas translaminar screws fixation has the advantages of firm fixation, simple operating techniques, and relative safety, so it may be a remedial measure of atlatoaxial instability.