Résumé
Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.
Sujets)
Humains , Pronostic , Ostéosarcome/génétique , Immunothérapie , Macrophages , Facteurs de transcription , Tumeurs osseuses/génétique , Protéines à homéodomaine , Protéines de répressionRésumé
The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.
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Osteosarcoma, originated from mesenchymal tissue, is one of the highest incidence of primary malignant bone tumors which were characteristic double peak distribution both in adolescents and elderly. Immune-targeted therapy could block the tumor cell signaling pathway and promote cancer cell death by apoptosis. Immune-targeted therapy is an effective treatment of anti-osteosarcoma after surgery and chemotherapy in recent years. The paper reviews the advances in latest research on the related mechanisms of the immune-targeted therapy on osteosarcoma, and hope to provide a theoretical basis for clinical treatment.
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<p><b>OBJECTIVE</b>To investigate effects of elastic stable intramedullary nails for the treatment of radial neck fracture in children.</p><p><b>METHODS</b>From July 2006 to December 2011, 25 children with radical neck fractures, which included 16 males and 9 females aged from 7 to 15 years old (means 10.7), were treated with elastic stable intramedullary nails. According to Judet classification, 6 cases were type II, 17 cases were type III and 2 cases were type IV (including 1 case with type IVa and 1 case with type IVb). The fracture healing, pain, deformity and range of motion of elbow were recorded.</p><p><b>RESULTS</b>All patients were followed up for 6 to 24 months with an average of 14 months. Twenty-five patients were obtained bone healing. According to Tibone and Stoltz evaluation standard, 18 cases got excellet results, 4 cases in good and 3 cases in moderate.</p><p><b>CONCLUSION</b>Elastic stable intramedullary nails for the treatment of radial neck fracture in children has advantages of simple operation,less trauma and good results.</p>
Sujets)
Adolescent , Enfant , Femelle , Humains , Mâle , Clous orthopédiques , Ostéosynthese intramedullaire , Fractures du radius , Chirurgie générale , Amplitude articulaire , Résultat thérapeutiqueRésumé
<p><b>OBJECTIVE</b>To investigate the apoptosis-inducing effect of nitidine chloride in human osteosarcoma MG-63 cells and explore its mechanism.</p><p><b>METHODS</b>The effect of nitidine chloride on the proliferation of MG-63 cells was detected by colorimetric MTT assay, and the morphological changes of cells treated with nitidine chloride were observed using fluorescence and electron microscope. Flow cytometry was performed to analyze the apoptotic rate of the cells, and the protein expression levels of caspase-3, caspase-9, Bcl-2 and Bax were detected by Western blotting.</p><p><b>RESULTS</b>Nitidine chloride inhibited the proliferation of MG-63 cells in a dose- and time-dependent manner. Fluorescence and electron microscopy revealed distinct apoptotic changes of the cells after nitidine chloride exposure. Flow cytometry indicated that nitidine chloride induced the apoptosis of MG-63 cells in a dose-dependent manner. Exposure to nitidine chloride, as shown by Western blotting, resulted in increased expressions of cleaved caspase-3, cleaved caspase-9 and Bax and decreased expressions of pro-caspase-3, pro-caspase-9 and Bcl-2.</p><p><b>CONCLUSION</b>Nitidine chloride can inhibit the proliferation of osteosarcoma cell line MG-63 by inducing cell apoptosis, the mechanism of which might be related with the activation of the caspase-dependent pathway.</p>