Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.
Bone Neoplasms/immunology* ; Computational Biology/methods* ; Gene Expression Profiling/methods* ; Humans ; Osteosarcoma/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Tumor-Associated Macrophages/immunology*

The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its dysregulation is associated with the proliferation, invasion, and migration of cancer cells. ERK1/2 is located at the distal end of this pathway and rarely undergoes mutations, making it an attractive target for anticancer drug development. Currently, an increasing number of ERK1/2 inhibitors have been designed and synthesized for antitumor therapy, among which representative compounds have entered clinical trials. When ERK1/2 signal transduction is eliminated, ERK5 may provide a bypass route to rescue proliferation, and weaken the potency of ERK1/2 inhibitors. Therefore, drug research targeting ERK5 or based on the compensatory mechanism of ERK5 for ERK1/2 opens up a new way for oncotherapy. This review provides an overview of the physiological and biological functions of ERKs, focuses on the structure-activity relationships of small molecule inhibitors targeting ERKs, with a view to providing guidance for future drug design and optimization, and discusses the potential therapeutic strategies to overcome drug resistance.

Objective:To investigate the mechanism of Wnt5a in lentoid body (LB) induction from human embryonic stem cells (hESCs).Methods:A "three-stage" protocol was used for LB differentiation from hESCs in vitro, and Wnt5a level was modified by adding exogenous 500 ng/ml Wnt5a on day 18 as Wnt5a treatment group.Cells of control group and Wnt5a treatment group were collected on day 35.Cells were photographed by using the Zeiss Axio Observer Z1 microscope.Transcriptome sequencing was applied by Illumina.Genes with P value≤0.05 and fold change≥1.5 were identified as differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to determine the biological functions of DEGs. Results:Compared with the control group, larger lentoid bodies were obtained in the Wnt5a treatment group.Transcriptome sequencing result showed that 478 genes were down-regulated and 201 genes were up-regulated in the Wnt5a treatment group compared with the control group, and Wnt5a up-regulated both lens cell differentiation and lens specific gene expression.Bioinformatics analysis result showed that most DEGs were involved in extracellular matrix remodeling, suggesting that Wnt5a regulated extracellular matrix remodeling during lens cell differentiation.The enrichment analysis result also showed that epithelial-to-mesenchymal transformation related processes were inhibited after Wnt5a treatment, suggesting that Wnt5a inhibited the abnormal differentiation of lens cells (especially lens epithelial cells) during lens cell differentiation.Wnt5a influenced the processes related to cytoskeleton remodeling.Conclusions:Wnt5a may act in lens cells through MAPK/ERK signaling pathways to affect ECM and cell cytoskeletal organization, which provides a new direction for studying lens development.

To explore the effect of application of soft tissue loosening and acetabular reconstruction in hip replacement for patients with severe femoral head necrosis on joint function.
 Methods: From June 2012 to August 2016, 68 patients with severe femoral head necrosis (Ficat III, IV) underwent total hip replacement with soft tissue release and acetabular reconstruction at the Second Xiangya Hospital of Central South University. Total hip replacement is performed by the posterolateral approach. The acetabulum was rebuilt and the length of the affected limb was prolonged after clearing the scar tissue, proliferating the epiphysis, releasing the abductor muscle group and the adductor muscle group, dissecting the soft tissue around the acetabulum. One year after surgery, Harris score, X-ray positive lateral radiograph for the affected side and full-length X-ray examination for both lower extremities were performed to evaluate the curative effect.
 Results: The postoperative follow-up time ranged from 1.0 to 5.5 years. All patients' femoral heads returned to normal anatomical position and the affected limb length was restored to 1.5-3.5 cm; all patients did not damage the sciatic nerve. The Harris scores for 68 patients increased from 38.6±7.5 to 78.2±5.7 (P=0.029) in the first year after surgery.
 Conclusion: During hip replacement surgery for severe femoral head necrosis, soft tissue dissection and acetabular reconstruction can be used to ensure anatomical reconstruction for the acetabular fossa and to improve abductor function.
Acetabulum ; Arthroplasty, Replacement, Hip ; Femur Head ; Femur Head Necrosis ; surgery ; Follow-Up Studies ; Humans ; Radiography ; Treatment Outcome

Objective:To explore the diagnostic value of 64‐slice spiral CT for in‐stent restenosis (ISR) after percuta‐neous coronary intervention (PCI) in patients with coronary heart disease (CHD) .Methods :A total of 120 CHD patients after PCI received 64‐slice spiral CT angiography and routine coronary angiography (CAG ) respectively . Then coronary ISR was assessed .Results:With CAG as the gold standard ,sensitivity ,specificity ,positive predictive value and negative predictive value were 87.5% ,95.3% ,80.0% and 97.3% respectively for 64‐slice spiral CT cor‐onary angiography in diagnosis of ISR .Conclusion :The 64‐slice spiral CT coronary angiography possesses high sensitivity and accuracy diagnosing coronary in‐stent restenosis ,which can be used as one of noninvasive measures for postoperative follow‐up after percutaneous coronary intervention .