BackgroundSIRT4 is a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes located in the mitochondria, and is involved in regulating energy metabolism, stress response, and cellular lifespan in mammalian cells. However, its function in human neuroblastoma (NB) remains unexplored.MethodsExpression of SIRT4 in 158 pairs of human NB tumor tissues and adjacent normal tissues collected from March 2009 to October 2012 was analyzed by immunohistochemistry, Western blotting, and real-time fluorescence quantitative PCR. For in vitro study, SIRT4 was overexpressed in SH-SY5Y, SK-N-BE, and IMR-32 cells to study the effects of SIRT4 expression on proliferation, invasion, and migration of human NB cells and on mitochondrial function.ResultsSIRT4 gene expression in human NB tumor tissues was significantly lower than that in adjacent normal tissues (P<0.001). SIRT4 expression was lower in NB patients with higher International Neuroblastoma Staging System stage (P=0.018), with lymph node metastasis, than patients without lymph node metastasis (P<0.001). Survival times of NB patients with low expression of SIRT4 were significantly shorter than those of patients with high expression of SIRT4 (P=0.0036). Overexpression of SIRT4 significantly reduced the proliferation, invasion, and migration ability of NB cells as well as mitochondrial energy production, and caused SIRT1 upregulation and mitochondrial damage in NB cells.ConclusionSIRT4 exhibits a tumor suppressor function in human NB and inhibits mitochondrial metabolism and SIRT1 expression in tumor cells, thereby reducing the energy metabolism of tumor cells. These results suggest that SIRT4 may be a new therapeutic target for human NB.
Background: Building an equitable health care system involves both the promotion of social justice in health and people's subjective perception of the promotion. This study aimed to analyze the overall status and associated factors of the perceived equity of the Chinese health care system, and then to offer policy recommendations for health care reform. Methods: Information on the perceived equity score (scale 0 to 10) of 10,243 valid cases in total were derived from the data set of Chinese Social Survey 2015. Univariate analysis methods were applied to present respondents' overall perceived equity of the Chinese health care system. Multivariate linear regression method was used to explore the associated factors of the perceived equity and examine their independent effect. Results: The respondents gave positive but relatively low marks (6.7 ± 2.6, 95% CI: = 6.64~6.74) of the equity of the Chinese health care system. Younger respondents reported a higher score of perceived equity than their elder counterparts (β = − 0.132, 95% CI: − 0.203~− 0.062, P < 0.001). Respondents with lower education level were significantly more likely to consider the Chinese health care system equitable (β = − 0.104, 95% CI: − 0.153~− 0.056, P < 0.001). Respondents satisfied with the Social Health Insurance reimbursement ratio tended to score the system higher in the survey (β = 0.044, 95% CI: 0.024~0.063, P < 0.001). Respondents residing in eastern China and rural areas were significantly more likely to consider the Chinese health care system equitable (β = − 0.268, 95% CI: − 0.338~− 0.199, P < 0.001). Meanwhile, rural respondents reported higher scores of the perceived equity than urban respondents did (β = 0.348, 95% CI: 0.237~0.458, P < 0.001). Respondents from regions with adequate GPs scored the system higher in this survey (β = 0.087, 95% CI: 0.008~0.165, P < 0.001). The present study found no influence of gender, economic status, Social Health Insurance coverage, or satisfaction with the latest treatment on perceived equity. Conclusions: Eliminating the sense of inequity among a range of populations should be prioritized in health care reform. A national-level investigation system to rate residents' perceived equity was necessary for global health care reform.
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