The Role of Purine Metabolism-Related Genes PPAT and IMPDH1 in the Carcinogenesis of Intrahepatic Cholangiocarcinoma Based on Metabonomic and Bioinformatic Analyses.

In this study, we investigated the role of tumor microenvironment and serum differential metabolites in intrahepatic cholangiocarcinoma (ICC) carcinogenesis, providing new evidence for ICC treatment. Serum samples from healthy individuals and ICC patients were collected for metabolomic analysis. The purine metabolites such as inosine, guanosine, hypoxanthine, and xanthine were increased in patient serum. TCGA database samples were collected, and the correlation between purine metabolism-related genes and ICC clinical features was analyzed using R language to obtain the differential genes including PPAT, PFAS, ATIC, and IMPDH2. High PPAT expression was associated with poor ICC prognosis. A PPAT silencing model in HCCC-9810 cells was constructed. The cell phenotype was examined by qRT-PCR, CCK-8, transwell, and flow cytometry, showing a decrease in IMPDH1 expression, colony and invasive cells numbers, and an increase in apoptosis. Guanosine reversed IMPDH1 expression in HCCC-9810 cells, promoting the secretion of inflammatory factors IL-6, IL-8, OPN, VEGF, and VCAM-1 and intensifying epithelial-mesenchymal transition (EMT) progression in the cells. In nude mice, the IMPDH1 inhibitory drug MMF inhibited tumor growth and reduced the expression of tumor stem cell characteristic markers CD133 and SOX2. Guanosine accelerated the malignant progression of ICC inhibition of purine metabolism-related genes, PPAT and IMPDH2, suppressed the malignant phenotype in HCCC-9810 cells, and inhibited tumor growth.

CXCR4/TGF-ß1 mediated hepatic stellate cells differentiation into carcinoma-associated fibroblasts and promoted liver metastasis of colon cancer.

Background: Liver metastasis of colon cancer is strongly affected by the tumor microenvironment (TME), with interactions between tumor cells and cancer-associated fibroblasts (CAFs) in particular. TGF-ß is well known for its ability to mediate the CAF phenotype, and CXCR4 expression is closely correlated to poor prognosis in CRC. The relationship between these two signaling pathways remains to be delineated in liver metastasis of colon cancer.Methods: Immunohistochemistry was employed to investigate CXCR4 expression in 45 human specimens of primary colorectal cancer (CRC) and liver metastasis. The functions of SDF-1 released by hepatic stellate cells (HSCs) on CXCR4 and TGF-ß1 in CRC cells were investigated in vitro. The effects of CRC on HSCs differentiation into CAFs were confirmed using co-culture technology and expression analysis of CAFs markers by qPCR, western blot and immunofluorescence. The involvement of CXCR4 and TGF-ß1 was verified with addition of CXCR4 inhibitor AMD3100 and TGF-ß1 inhibitor cyclophosphamide (Cy) both in vitro and in vivo.Results: There were more CXCR4-positive cells at the liver metastatic tissues compared to the primary sites. CRC cells activated and transformed HSCs to CAFs after co-cultivating with HSCs. Activated HSCs stimulated TGF-ß1 secretion from CRC cells after co-culture with CRC cells in vitro. Moreover, the expression of CAFs markers was increasing in the activated HSCs. In a mouse hepatic metastasis model, treated with AMD3100 or Cy blocked the metastatic potential of HCT116 cells and the hepatic CAFs differentiation.Conclusions: These results indicated that CXCR4/TGF-ß1 axis plays an important role in CRC liver metastasis through mediating HSCs differentiation into CAFs, providing preclinical evidences that blockade of the axis might be beneficial for anti-metastasis therapy in CRC.

[Analysis on physical and mental health and related influential factors among those 'left behind' adolescents in Anhui province].

OBJECTIVE: To explore the physical and mental health status on the 'left behind' students in Anhui province and the related influential factors. METHODS: Stratified cluster sampling method was used to investigate the 682 out of 3421 students from 7 middle schools in both south and north Anhui province, using multidimensional sub-health questionnaire of adolescents (MSQA) and mental health test (MHT), for assessment of the general condition, physical and mental health status. RESULTS: 14.22% of the 'left behind' students were in sub-health condition compared to 11.28% among the normal students, and the mental sub-health status represented 13.64% for the former and 10.84% for the latter. In addition, the 'left behind' students appeared less content with their life than those of staying with their parents (P < 0.05). MHT scores in the subjects were positively correlated with the scores on MSQA and showed significant difference (P < 0.01). RESULTS: from the multiple linear regression analysis showed that the mental health condition among the left behind students was in linear regression relationship with the decreased physical activity (ß = 1.456, P = 0.001), emotional problems (ß = 1.096, P = 0.000) and problems of social adaptation (ß = 1.011, P = 0.006). The status of physical sub-health in the Anhui province showed that there was no significant difference in each of the study group (P > 0.05). CONCLUSION: Decreased physical activity and emotion aporia as well as difficult social adaptation were major factors leading to degenerated mental health levels in the 'left-behind' adolescents. The findings suggested that the mental health status could be improved in this population through better management on their body-health condition.

[A prevalence survey on the mental health of left behind adolescent in Anhui province].

OBJECTIVE: By exploring the mental health situation of the unattended adolescents in Anhui province. This study aimed at investigating the status of mental health and related influential factors to provide evidence for effective strategies and intervention in physical and mental health improvement of this population. METHODS: By using stratified cluster sampling method, we conducted an investigation on 3421 subjects, in which 682 were unattended adolescents, from 7 middle schools in both south and north parts of Anhui province. MHT was used to assess the general condition and status of mental health in the adolescents. RESULTS: In the population aged 10 to 18 in Anhui province, 19.94% of them were unattended adolescents and were found with poor mental health and more prone to loneliness, sensitive and stronger fear as compared with those with parents around, which showed statistical difference (P < 0.05). As for the mental health status of unattended adolescents in different family types, the subjects seemed worse in the north than in the south Anhui regarding the total scores of MHT, self-accusation, physical symptoms and phobic anxiety disorder (P < 0.05). Girl students were also inferior to boys concerning the total scores of MHT, learning anxiety, interpersonal anxiety, self-accusation, sensitivity, physical symptoms and impulsive behavior (P < 0.05). The students in Grade 7 scored lower than those of the upperclassmen on MHT (P < 0.05), and the subjects from township were superior to those of rural areas regarding interpersonal anxiety and loneliness (P < 0.05). Children with siblings appeared worse than their counterparts on the total scores of MHT, including the items of interpersonal anxiety, learning anxiety, self-accusation, sensitivity, physical symptoms, strong fear and impulsive behavior (P < 0.05). CONCLUSION: Generally, the mental health status of unattended adolescents in Anhui province appeared poorer than their counterparts, and relatively worse psychological status was seen in girls, high school students, children with siblings and subjects living in north Anhui or rural areas.