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Osteosarcoma is generally considered a cold tumor and is characterized by epigenetic alterations. Although tumor cells are surrounded by many immune cells such as macrophages, T cells may be suppressed, be inactivated, or not be presented due to various mechanisms, which usually results in poor prognosis and insensitivity to immunotherapy. Immunotherapy is considered a promising anti-cancer therapy in osteosarcoma but requires more research, but osteosarcoma does not currently respond well to this therapy. The cancer immunity cycle (CIC) is essential for anti-tumor immunity, and is epigenetically regulated. Therefore, it is possible to modulate the immune microenvironment of osteosarcoma by targeting epigenetic factors. In this study, we explored the correlation between epigenetic modulation and CIC in osteosarcoma through bioinformatic methods. Based on the RNA data from TARGET and GSE21257 cohorts, we identified epigenetic related subtypes by NMF clustering and constructed a clinical prognostic model by the LASSO algorithm. ESTIMATE, Cibersort, and xCell algorithms were applied to analyze the tumor microenvironment. Based on eight epigenetic biomarkers (SFMBT2, SP140, CBX5, HMGN2, SMARCA4, PSIP1, ACTR6, and CHD2), two subtypes were identified, and they are mainly distinguished by immune response and cell cycle regulation. After excluding ACTR6 by LASSO regression, the prognostic model was established and it exhibited good predictive efficacy. The risk score showed a strong correlation with the tumor microenvironment, drug sensitivity and many immune checkpoints. In summary, our study sheds a new light on the CIC-related epigenetic modulation mechanism of osteosarcoma and helps search for potential drugs for osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Objective: To improve the retrograde rotative-type interlocking intramedullary nail based on humeral bone dissection and clinical application, and investigate the clinical values of modified retrograde rotative-type interlocking intramedullary nail for humeral shaft fracture., Methods: Between March 2006 and March 2010, 146 patients with humeral shaft fractures were treated and fractures were fixed with the modified retrograde rotative-type interlocking intramedullary nail (the modified group, n=73) and with the retrograde rotative-type interlocking intramedullary nail (the original group, n=73). In the original group, there were 40 males and 33 females with an average age of 41 years; 41 cases were classified as transverse fracture, 18 as oblique fracture, 8 as spiral fracure, and 6 as comminuted fracture; the median disease duration was 11 days (range, 3 hours to 2 months); and close reduction fixation was performed in 27 cases and open reduction fixation in 46 cases. In the modified group, there were 39 males and 34 females with an average age of 40 years; 43 cases were classified as transverse fracture, 16 as oblique fracture, 10 as spiral fracure, and 4 as comminuted fracture; the median disease duration was 13 days (range, 3 hours to 3 months); and close reduction fixation was performed in 31 cases and open reduction fixation in 42 cases. There was no significant difference in sex, age, fracture type, and disease duration between 2 groups (P > 0.05). The fracture healing and functional recovery of affected limbs were compared between 2 groups after operation., Results: The operation time and intraoperative blood loss in the modified group were significantly less than those in the original group (P < 0.05). Iatrogenic fracture occurred in 3 cases of the original group, which were cleavage fracture of supracondylar. No iatrogenic fracture occurred in the modified group. All incisions of 2 groups healed by first intention without complications of postoperative infections, metal fracture, and loosening of internal fixation, etc. A total of 116 patients were followed up more than 12 months in 2 groups with 58 patients in each group. The fracture healing time was (15 +/- 3) weeks (fresh fracture) and (30 +/- 12) weeks (old fracture and nonunion) in the modified group, and was (16 +/- 4) weeks (fresh fracture) and (35 +/- 14) weeks (old fracture) in the original group, showing significant differences between 2 groups (P < 0.05). The results of Neer shoulder score were excellent in 65 cases and good in 8 cases, and the results of Aitken and Rorabeck elbow function score were excellent in 61 cases and good in 12 cases in the original group; the results of Neer shoulder score were excellent in 67 cases and good in 6 cases, and the results of Aitken and Rorabeck elbow function score were excellent in 63 cases and good in 10 cases; and the excellent and good rates were 100% in 2 groups., Conclusion: The modified retrograde rotative-type interlocking intramedullary nail has the advantages of easy operation and less complication, which is an effective and reliable internal fixator.