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Background: Immunogenic cell death (ICD) is related to cancer prognosis, which has a synergic effect in combination with chemotherapy or immunotherapy. Yet, the relationship between ICD and osteosarcoma remained unclear. Materials and methods: Three osteosarcoma datasets including therapeutically applicable research to generate effective treatments (TARGET), GSE126209 and GSE21257 datasets were included. A protein-protein interaction network was constructed based on ICD-related genes. We performed unsupervised consensus clustering to classify molecular subtypes (clusters). Survival analysis, Estimation of stromal and immune cells in malignant tumour tissues using expression data (ESTIMATE), Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), and differential analysis were employed to characterize the molecular differences between different clusters. Univariate Cox regression analysis was conducted to confirm prognostic genes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to demonstrate the aberrant expression of ICD-correlated signature genes in osteosarcoma. A series of cellular experiments, including cell counting kit-8 (CCK-8), transwell, and flow cytometry, were used to demonstrate the regulatory role of key genes in the ICD model on the malignant phenotype of osteosarcoma. Results: Three clusters (cluster1, 2, 3) were constructed and they showed distinct overall survival and immune infiltration. ICD-related genes were highly expressed in cluster1. Moreover, Cluster1 had the best prognosis, high immune score and high expression of human leukocyte antigen (HLA)-related genes. TLR4, LY96, IFNGR1, CD4, and CASP1 were identified as prognostic genes for establishing an ICD-related risk signature. According to the risk signature, two risk groups (high and low risks) showing differential prognosis and response to immunotherapy. The low risks group had a better prognosis but was not sensitive to immunotherapy. Molecular assays verified that prognostic genes were abnormally under-expressed in osteosarcoma. Cellular assays demonstrated that LY96, the most significantly down-regulated gene in osteosarcoma, inhibited the migration, invasion, and proliferation phenotypes of osteosarcoma cells and prolonged the cell cycle. Analysis of oxidative stress related pathway enrichment in tumor microenvironment was conducted by single-sample gene set enrichment analysis (ssGSEA). Conclusions: This study demonstrated the prognostic significance of ICD-correlated genes in osteosarcoma patients. The five-gene risk signature facilitate prognostic evaluation and prediction of osteosarcoma patients' response to immunotherapy. The risk signature also offered a possibility for the exploit of novel ICD-related treatment.
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Introduction: In recent years, a growing number of near-death experience (NDE) testimonies have been collected worldwide due to an increasing interest in research on this phenomenon. China has many patients who survive life-threatening situations, leaving over much data on NDEs to be collected for research. In the historical context of Eastern civilization, many mentally controlled practices in China can also lead to "NDEs-like" (e.g., meditation). This study aimed (1) to translate and validate the recently developed Near-Death Experience Content (NDE-C) scale into Chinese and (2) to quantify and identify NDEs and NDEs-like in China with this new Chinese version of the NDE-C scale. Methods: Here, we presented the work that had been performed to translate the NDE-C scale into Chinese and validated this version on 79 NDE testimonies. Results: Brislin's back-translation model was performed to translate a Chinese version of the NDE-C scale and internal consistency (the Cronbach's α value for the total group = 0.846) as well as the confirmatory factor analysis was conducted. Discussion: Currently, the Chinese version of the NDE-C scale is ready for use in research practice in the context of Eastern culture, to screen people who have experienced an NDEs(-like) and to quantify their subjective experience, promoting further NDEs-related research in China.
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BACKGROUND: The circular RNA (circRNA) antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as)/micro RNA-7(miR-7) signal axis has been investigated in many diseases via regulation of the target genes of miR-7, which participates in the carcinogenesis and metastasis. However, the clinical role and function of CDR1as/miR-7 pathway in osteosarcoma (OS) remain to be identified. MATERIALS AND METHODS: Noncancerous bone tissues (n=18) and OS tissues (n=38) were used to determine the expressions and roles of CDR1as and miR-7. We knocked down the expression of CDR1as via siRNAs in OS cell lines to analyze its function in vitro and in vivo. RESULTS: CDR1as was upregulated in OS tissues with significant diagnostic value (cutoff value: 1.613). OS patients with high tumor size, Enneking stage, and distant metastasis have high CDR1as levels, but the miR-7 as tumor suppressor negatively correlated with CDR1as. Inhibition of CDR1as in OS cell lines U2OS and MG63 with high CDR1as levels, leading to de-repressed miR-7 levels, impaired cell vitality and increased apoptosis and G1/S arrest in parallel with reduced ability of cell migration, which, however, could be restored by miR-7 inhibitor. Mechanistically, knockdown of CDR1as could restore the availability of miR-7 and inhibit the target genes of miR-7 including EGFR, CCNE1, PI3KCD, and RAF1. Moreover, CDR1as also upregulated N-cadherin and inhibited E-cadherin to promote the epithelial-mesenchymal transition via miR-7 for cell migration. CDR1as inhibition in vivo also induced tumor regression with decreased PCNA levels, and miR-7 inhibitor could reverse these effects via upregulation of EGFR, CCNE1, PI3KCD, and RAF1. The expressions of these genes were confirmed to be higher in CDR1as-high OS samples than in CDR1as-low OS samples. CONCLUSION: These findings suggested that the CDR1as/miR-7 signal axis could be the molecular target for the treatment of OS.
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OBJECTIVE: To explore the value of electromagnetic navigation interlocking intramedullary nail in the treatment of femoral shaft fracture. METHODS: Between July 2012 and October 2013, 53 cases of femoral shaft fracture were treated. There were 40 males and 13 females, aged 16-52 years (mean, 38.3 years). The causes of injury were traffic accident in 28 cases, falling from height in 11 cases, falling in 7 cases, crush injury in 4 cases, and other in 3 cases. Of 53 cases, there were 3 cases of open fracture (Gustilo I degree) and 50 cases of closed fracture. Fracture was located in the proximal femur in 17 cases, middle femur in 29 cases, and distal femur in 7 cases. According to Winquist classification, 7 cases were rated as type I, 8 cases as type II, 22 cases as type III, and 16 cases as type IV; according to AO classification, 18 cases were rated as type 32-A, 28 cases as type 32-B, and 7 cases as type 32-C. The time from injury to operation was 3-11 days (mean, 5 days). Distal interlocking intramedullary nail was implanted using electromagnetic navigation. RESULTS: The distal locking nail operation with interlocking intramedullary nail was successfully completed under electromagnetic navigation; the one-time success rate of distal locking nail operation reached 100%; and the locking nail time was 5.0-9.5 minutes (mean, 7.0 minutes). Healing of incision by first intention was obtained after operation, and no complication of skin necrosis, infection, and sinus tract occurred. Fifty-three cases were all followed up 5-12 months (mean, 9 months). One case had hip pain and weaken middle gluteal muscle strength, and the symptoms disappeared after removing the nail. During the follow-up period, no broken nails, nail exit, infection, or re-fracture occurred. All fractures achieved clinical healing, and the healing time was 8-22 weeks (mean, 14.5 weeks). In 49 patients followed up 8 months, the Lysholm score was excellent in 44 cases, good in 4 cases, and acceptable in 1 case, with an excellent and good rate of 98%. CONCLUSION: Electromagnetic navigation system is safe and reliable, with the advantages of high positioning accuracy, short operation time, and no radiation, the clinical application of the system for distal locking nail operation can obtain excellent short-term effectiveness.
