ABSTRACT
High-altitude hypoxia exposure can lead to phospholipase D-mediated lipid metabolism disorder in spleen tissues and induce ferroptosis. Nonetheless, the key genes underlying hypoxia-induced splenic phospholipase D and the ferroptosis pathway remain unclear. This study aimed to establish a hypoxia animal model. Combined transcriptomic and proteomic analyses showed that 95 predicted target genes (proteins) were significantly differentially expressed under hypoxic conditions. Key genes in phospholipase D and ferroptosis pathways under hypoxic exposure were identified by combining Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis techniques. Gene set enrichment analysis (GSEA) showed that the differential gene sets of the phospholipase D and ferroptosis signaling pathways were upregulated in the high-altitude hypoxia group. The genes in the phospholipase D signalling pathway were verified, and the expression levels of KIT and DGKG were upregulated in spleen tissues under hypoxic exposure. Subsequently, the mRNA and protein expression levels of genes from the exogenous pathway such as TFRC, SLC40A1, SLC7A11, TRP53, and FTH1 and those from the endogenous pathway such as GPX4, HMOX1, and ALOX15 differentials in the ferroptosis signalling pathway were verified, and the results indicated significant differential expression. In summary, exposure to high-altitude hypoxia mediated phospholipid metabolism disturbance through the phospholipase D signalling pathway and further induced ferroptosis, leading to splenic injury.
ABSTRACT
Abstract Objective To explore the effect of surgical treatment and related prognostic factors for recurrent Nasopharyngeal Carcinoma (NPC) after radiotherapy and the pathological types of nasopharyngeal carcinoma insensitive to radiotherapy. Methods A total of 70 NPC patients who underwent surgery at the Department of Otolaryngology, head and neck surgery, from January 2005 to December 2020 were retrospectively included: 41 males and 29 females, aged 21-75 years, 47 patients were pathologically classified as NPC (nonkeratinizing, undifferentiated type), 10 patients as adenoid cystic carcinoma, 13 patients as other types, 45 patients had received radiotherapy preoperatively, and 25 patients had not received radiotherapy preoperatively. All patients underwent surgical treatment under general anesthesia. Fifty-six patients underwent nasoendoscopic NPC resection, seven patients underwent open surgery, and seven patients underwent combined nasoendoscopic and open surgery. The median follow-up was 39 months. Tumor volume, extent of involvement, lymph node metastasis, imaging characteristics, surgical approach and efficacy, postoperative complications, and 2-, 3-, and 5-year postoperative survival rates were calculated for all patients. Statistical analysis was performed using spss22 Kaplan Meier survival analysis and Cox regression analysis were performed. Results Among the 70 patients, the overall 2-year survival rate was 93.4%, the 3-year survival rate was 90.8%, and the 5-year survival rate was 80.3%. Multivariate analysis showed that TNM stage and age at onset were independent prognostic factors for NPC outcome. Conclusion Depending on the size and location of the tumor, endoscopic surgery, open surgery, and combined open surgery with nasoendoscopy may be considered for recurrent and radiotherapy insensitive NPC. Level of Evidence: Level 4.