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Objective: The aim of this study was to investigate sclerostin (SOST) expression in a rat model of experimental tympanosclerosis (TS) and its possible role in the formation of TS. Materials and Methods: Thirty-four SD rats were randomly divided into 2 groups: experimental group (n = 17) and normal group (n = 17). The left tympanic cavities in the experimental group were inoculated with methicillin-resistant Staphylococcus aureus. The changes of tympanic membranes were examined and recorded under otoendoscope. Haematoxylin-eosin staining was adopted to detect the morphological changes in the tympanic membrane and middle ear mucosa. Immunohistochemistry and Western blot analysis were used to observe the expression of SOST, Wnt3a, β-catenin, and P-ERK1/2. Results: In the experimental group, sclerotic lesions were observed in 54.5% ears in the end of 6 weeks. Morphological changes such as mucosa incrassation, inflammatory cells infiltration, fibrous tissue proliferation, and interstitial tissue incrassation prominently appeared in the tympanic membrane and middle ear mucosa. SOST protein was mainly distributed in the cytoplasm of epithelial cells and gland cells, the expression of which increased significantly in the calcified experimental ears. In addition, expression levels of Wnt3a, β-catenin, and P-ERK1/2 increased significantly in the calcified group too. Conclusion: The upregulated expression level of SOST may be involved in the formation of TS, first, through the pro-phosphorylation of ERK1/2 in the inflammatory stage, and then through the enhancement of Wnt3a in the osteogenic stage. [ABSTRACT FROM AUTHOR]

Purpose: There have been many attempts to preoperatively evaluate the chemotherapy response of osteosarcoma patients using 99m Tc-MIBI scintigraphy. However, the evaluations were lacking in consistency. We performed this systematic review and meta-analysis to systematically evaluate the ability of 99m Tc-MIBI scintigraphy in preoperatively assessing the response of osteosarcoma patients to neoadjuvant chemotherapy. Methods: For this systematic review and meta-analysis, PubMed, Web of Science, OVID, the Cochrane Library, and CNKI were searched. Eligible studies were included based on the defined criteria. The index test was 99m Tc-MIBI scintigraphy, the reference standard was tumor necrosis rate. Quality Assessment of Diagnostic Accuracy Studies-2 was adopted for quality assessment of included studies. The statistical pooling analysis, meta-regression analysis, subgroup analysis, sensitivity analysis, and publication bias of our research were performed using STATA 15. Results: Eight articles with 189 osteosarcoma patients were included in this systematic review and meta-analysis. Our results demonstrated that the threshold effect of our meta-analysis was significant. The uptake change ratio of 99m Tc-MIBI scintigraphy had a pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and the area under curve of 0.98 (0.58-1.00), 0.68 (0.47-0.84), 3.1 (1.7-5.5), 0.03 (0.00-0.90), 103 (4-3,003), and 0.91 (0.88-0.93) in preoperative assessment of response of osteosarcoma patients to neoadjuvant chemotherapy. Meta-regression analysis and subgroup analysis indicated the factors of method and cut off value may introduce the heterogeneity. The pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and the area under curve of washout rate of 99m Tc-MIBI were 0.87 (0.69-0.95), 0.91 (0.75-0.97), 9.3 (3.2-27.0), 0.15 (0.06-0.37), 64 (14-301), and 0.89 (0.86-0.92), respectively. Sensitivity analysis and publication bias demonstrated our meta-analysis was reliable. Conclusion: Both the ΔUR and WR derived from 99m Tc-MIBI scintigraphy were valuable in preoperatively assessing the response of osteosarcoma patients to neoadjuvant chemotherapy, and ΔUR may possess a more outstanding diagnostic accuracy than WR., (Copyright © 2020 Wu, Huang, Huang, Fang, Huang, Huang, Zhang and Shao.)