ABSTRACT
As an essential trace element in living organisms, copper is actively involved in normal physiological processes in various systems and is maintained at low level to achieve copper homeostasis. Copper homeostasis, once being disrupted, would induce cell death, and this new form of cell death is known as copper death. In recent years, copper death has been increasingly recognized as an important factor mediating the onset and progression of central nervous system (CNS) diseases. Therefore, we review the pathogenic mechanism of copper death in CNS diseases, as well as its therapeutic strategies so as to deepen the understanding of researchers.
ABSTRACT
Objective:To analyze the expression of structural maintenance of chromosome 4( SMC4) gene in glioma and its clinical significance. Methods:(1) The SMC4 mRNA expression data of 749 glioma tissues and clinical data of these glioma patients were downloaded from Chinese Glioma genome Atlas (CGGA) database. Univariate Cox analysis and multivariate Cox analysis were used to analyze the independent influencing factors for poor prognosis in patients with glioma. Patients were divided into high SMC4 mRNA expression group and low SMC4 mRNA expression group; Kaplan-Meier method was used to draw the survival curve of these patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of SMC4 mRNA in 1-, 3- and 5-year survival of these patients. (2) The relationships between SMC4 mRNA expression levels in glioma tissues from cancer Genome Atlas (TCGA) database and overall survival of these glioma patients were analyzed by gene expression profiling interactive analysis (GEPIA). The SMC4 protein expressions in high-grade glioma (glioblastoma) and low-grade glioma were determined by human protein atlas (HPA) online database. (3) Genomic enrichment analysis was used to analyze and compare the differences of gene body (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway in gliomas between SMC4 mRNA high expression group and SMC4 mRNA low expression group. Co-expression analysis was performed to analyze the genes related to SMC4 mRNA. Results:(1) Multivariate Cox analysis showed that SMC4 mRNA ( HR=1.314, 95%CI: 1.209-1.428, P=0.000), glioma primary-recurrent-secondary (PRS) type, glioma WHO grading, age, chemotherapy, isocitrate dehydrogenase ( IDH) mutation and 1P/19q deletion were independent influencing factors for poor prognosis of glioma patients. Survival analysis showed that the overall survival of patients with low SMC4 mRNA expression was significantly higher than that of patients with high SMC4 mRNA expression ( P<0.05). The area under the curve (AUC) of ROC was 0.712, 0.784 and 0.791, respectively, in predicting 1-year survival rate, 3-year survival rate and 5-year survival rate. (2) SMC4 mRNA expressions in low-grade and high-grade gliomas were statistically lower than those in normal control brain tissue ( P<0.05). The overall survival of low-grade glioma patients with low SMC4 mRNA expression was significantly higher than that of patients with SMC4 mRNA high expression ( P<0.05). There was no significant difference in overall survival between high-grade glioma patients with low SMC4 mRNA expression and high SMC4 mRNA expression ( P>0.05). The SMC4 protein expression in low-grade glioma was significantly higher than that in high-grade glioma. (3) Genome enrichment analysis showed that GO enriched in gliomas with high SMC4 mRNA expression was about nuclear chromosome aggregation, protein complex driving, cell cycle meiotic and process of meiotic cell cycle. KEGG enrichment included cell cycle, DNA replication, mismatch repair, P53 signaling pathway, pancreatic cancer and other related pathways. Gene co-expression analysis showed that the first 5 genes, including BUB1, WEE1, CENPL, KIF23 and SGOL2, were positively correlated with SMC4 mRNA expression; and the first 5 genes, including FBXW4, PNMAL2, MATK, PASL10A and CTD-2210P24.4, were negatively correlated with SMC4 mRNA expression. Conclusions:Glioma patients with SMC4 mRNA high expression have poor prognosis. As a high risk factor, SMC4 mRNA can be used as an independent prognostic indicator of glioma patients, and its biological function is related to DNA replication of glioma.
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Objective To introduce two modified surgical procedures for the treatment of chronic subdural hematoma (CSDH) and explore their clinical efficacies. Methods The clinical data of 100 CSDH patients, admitted to our hospital from March 2012 to February 2017, were retrospectively analyzed. Hematoma evacuation plus T-tube drainage was performed in 43 patients and minimally invasive microsurgery in 57 patients. Follow up of treatment efficacies was performed. Results During surgery, hematoma drainage of 5 patients (5%) was poor and the removal of hematoma was expanded. The clinical symptoms and signs of all of the patients improved after operation. Postoperative 24 h CT indicated that the ipsilateral subdural subdural effusion was found in 36 patients (36%), a small amount of ipsilateral subdural air was found in 13 patients (13% ), and a small amount of residual hematoma was found in 6 patients (6%). Follow up for 3-6 months indicated that subdural subdural effusion, subdural air and residual hematoma were absorbed completely; no hematoma recurrence, intracranial infection, scalp incision infection or death were noted; contralateral chronic subdural hematoma was found in one patient (1%), and hematoma was absorbed after conservative treatment. Clinical symptoms and signs of all patients were significantly improved and disappeared. Conclusion The minimally invasive double-hole hemodilution assisted with T-tube wall-draining or minimally invasive hematoma evacuation can effectively treat CSDH, and the postoperative complications are few;the above two surgical methods are worthy of clinical use, especially application and popularization of primary hospital.