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Objective:The feasibility of curative surgery for elderly patients with renal cell carcinoma (RCC) remains controversial and under discussion. The main aim of this study was to evaluate the long-term benefits of curative surgery as a treatment for RCC in elderly patients.Methods:We retrospectively considered 672 patients with RCC who underwent partial nephrectomy or radical nephrectomy between January 2004 and July 2014. X-tile program was used to determine the optimal age cutoff values with CSS as endpoint.Results:Patients were divided into the following groups according to their age using the method of X-tile program: a young group (< 40 years), a young-old group (40-75) and an old-old group (≥ 75). Following multivariate analysis age ≥ 75 years was determined to be an independent risk factor for overall survival (HR=4.36; 95% CI: 1.31-14.48; P=0.016); interestingly, this was not the case for cancer-specific survival (HR = 2.65; 95%CI: 0.77-9.16; P=0.124). Furthermore, an age of 40 to 75 years was not a risk factor according to univariate and multivariate analysis.Conclusion:After determining the age cutoff values, there was no significant difference in prognosis between young and old patients with RCC.

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Toxoplasma gondii excreted-secreted antigens (ESA) could lead to the fetal abortion especially in the early stage of pregnancy. Deficit in regulatory T cells is a critical event in the fetal abortion. Transcription factor forkhead box p3 (Foxp3) mediates differentiation and functional roles on regulatory T cells. Previously, we revealed that ESA inhibited Foxp3 through the suppression of transforming growth factor-β type II receptor, phosphorylation of Smad2, Smad3, and Smad4. Knockdown of Smad2 collaborated with ESA to further inhibit Foxp3. The decrease in Foxp3 caused by ESA reversed via forced expression of Smad2, Smad3, and Smad4, respectively. In this study, we investigate whether other signaling pathways are implicated in ESA-induced Foxp3 downregulation. EL4 cells were cultured and stimulated with ESA. Interleukin-2 receptor γ (IL-2Rγ) chain, Janus kinase 3 (JAK3), signal transducer and activator of transcription 5 (Stat5), Stat3, phosphorylation of Stat5 and Stat3 were assayed by Western blot analysis. Phosphorylation of Stat5 and Stat3 was further measured by cellular immunofluorescence. The expression plasmid of pcDNA3.1-Stat3 and pcDNA3.1-Stat5b was constructed, respectively. The concentration of interleukin-2 (IL-2) in the culture supernatants was detected by enzyme-linked immunosorbent assay. ESA inhibited the level of JAK3, phosphorylation of Stat5 and Stat3, and Foxp3 in EL4 cells. The suppressive effects of ESA on Foxp3 were attenuated by forced expression of Stat5 and Stat3. In addition, ESA suppressed IL-2Rγ in EL4 cells, while IL-2Rγ agonist could markedly reverse the diminished Foxp3 caused by ESA. Furthermore, ESA directly influenced the expression of IL-2Rγ, rather than the availability of IL-2 indirectly. ESA suppressed the level of Foxp3 via inhibiting IL-2Rγ/JAK3/Stats signaling pathway in EL4 cells.

Toxoplasma gondii excreted‐secreted antigens (ESA) cause spontaneous abortion or fetal teratogenesis during the pregnancy in mice, especially in the early stage. Those adverse pregnancy outcomes are due to the deficit in regulatory T cells (Tregs). Forkhead box P3 (Foxp3), a critical transcription factor, modulates Tregs differentiation and its function. Besides, phosphatidylinositol 3‐kinase‐protein kinase B‐mammalian target of rapamycin (PI3K‐AKT‐mTOR) signaling network is implicated in interfering with Foxp3 induction. We previously demonstrated that ESA diminished the number of Tregs and inhibited its function. And ESA suppressed Foxp3 expression via the attenuation of transforming growth factor β RII/Smad2/Smad3/Smad4 pathway. The current study aimed to investigate whether the PI3K‐AKT‐mTOR signaling network is involved in Foxp3 downregulation induced by ESA. We found that ESA upregulated PI3K, P‐AKT, mTOR, and P‐mTOR. Knockdown of PI3K cooperated with ESA to restore Foxp3 expression mediated by ESA. This suppressive role of ESA on Foxp3 expression was abrogated by AKT inhibitor. In addition, neutralization of Toll‐like receptor 4 could restore the expression of Foxp3, PI3K, and its downstream effectors induced by ESA. Collectively, the findings indicated that ESA inhibited Foxp3 expression via the upregulation of PI3K‐AKT‐mTOR signaling pathway.

Purpose: The expression and clinical value of zinc finger protein 2 gene (ZIC2) in hepatocellular carcinoma (HCC) were analyzed by mining gene information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Methods: Gene chip data sets were retrieved from GEO and TCGA and screened for differentially expressed genes in HCC. Gene expression profile interaction analysis (GEPIA) and Kaplan–Meier curves were used to analyze the relationship between differentially expressed genes (DEGs) and survival and prognosis in patients with HCC. Moreover, the Genecards database was used to extract ZIC2-related proteins and to analyze the physiological process of protein enrichment. Furthermore, the relationships between ZIC2 gene and tumor cell immune invasion and that between immune cell infiltration and the 5-year survival rate were studied using the tumor immune evaluation resource (TIMER) database. Results: Datasets from GEO and TCGA revealed that ZIC2 was differentially expressed in HCC tissues and normal tissues (P&lt;0.05). High ZIC2 expression was associated with overall survival (OS) and progress-free survival in HCC patients. Overall, 25 ZIC2 related proteins, including Gli3, PRKDC, and rnf180 were identified and protein enrichment analysis indicated these were associated with four types of cell components, six types of cell functions, and eight types of biological processes. ZIC2 was positively correlated with immune infiltration cells in patients with HCC, and higher expression of ZIC2 mRNA CD4+T cells is associated with a better 5-year survival. Conclusion: ZIC2 gene may be used as an immune response marker in liver cancer to predict the prognosis of HCC.

Abstract. The present retrospective study aimed to investigate the mid-term safety and efficacy of hepatectomy combined with microwave ablation of the partial spleen for treatment of liver cancer complicated with hypersplenism. A retrospective analysis was performed on 23 patients who underwent hepatectomy combined with microwave ablation of the partial spleen for liver cancer, complicated with hypersplenism that was secondary to cirrhosis. The splenic and ablated volumes were calculated according to a contrast-enhanced computed tomography scan prior to and 2 weeks after the operation. Complete blood count and liver function tests were examined prior to and following the surgery, and complications and changes in the blood tests were monitored for 6 months. Over this period of investigation, the splenic volume was reduced by a mean value of 34.0%. The levels of serum alanine aminotransferase and aspartate aminotransferase were increased on the first day after the operation (P<0.05), although they recovered to the normal level within 1 week (P<0.05). The total level of bilirubin increased slightly, along with moderately decreased levels of albumin and cholinesterase on the first day, although these changes were not significant compared with the baseline (P>0.05). The white blood cell count was persistently significantly higher compared with the baseline over the course of the 6 months (P>0.05). The platelet count did not increase significantly for the first week after the operation (P>0.05); however, it was revealed to be significantly increased 1 month after the surgery (P<0.05). No significant complications were occurred during the follow-up period. In conclusion, hepatectomy combined with microwave ablation of the spleen was demonstrated to be a safe and effective procedure for patients with liver cancer and hypersplenism in the mid-term.