Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl₂ and hypoxia (1%O₂) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl₂ and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.
Humans ; Carcinoma, Renal Cell/pathology* ; Kidney Neoplasms/pathology* ; HeLa Cells ; Von Hippel-Lindau Tumor Suppressor Protein/genetics* ; Mutation ; Signal Transduction ; Luciferases/therapeutic use* ; Hypoxia/genetics* ; RNA, Messenger ; Lipids/therapeutic use* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

Objective: To clarify the values of autotaxin (ATX) in patients with primary biliary cholangitis (PBC) and PBC-related hepatocellular carcinoma (HCC). Methods: 179 patients with PBC were selected from prospective cohorts of autoimmune liver diseases at the time of first diagnosis of PBC in Department of Hepatology, the Fifth Medical Center of PLA General Hospital, from January 2016 to January 2018, all patients with PBC received UDCA therapy, primary endpoint was event of HCC, the follow-up period was censored at the date of HCC. The relationship between level of ATX and clinical features in patients with PBC and its potential value in predicting disease progression and PBC-related HCC were analyzed. Results: The ATX level in the peripheral blood of patients with PBC was significantly higher than that of alcoholic liver cirrhosis(ALC) (t = 3.278, P = 0.001) and healthy controls(HC) (t = 6.594, P < 0.001), however, when comparing PBC to non-PBC related HCC, no significant difference was found between the groups(t=-0.240, P = 0.811). Consistent with peripheral blood levels, histochemical staining indicated that ATX in the liver of patients with PBC was significantly higher than that of HC (Z=-3.633, P < 0.001) and ALC (Z=-3.283, P < 0.001), and the expression of ATX in PBC with advanced histological stage was significantly higher than PBC with early stage (Z=-2.018, P = 0.034). The baseline ATX level in PBC patients without developing to HCC during follow-up had significant difference to patients with developing to HCC (228.451 ± 124.093 ng/ml vs 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). The result in multivariate logistic regression analysis showed that ATX were independent predictors of PBC related HCC(OR 1.245, 95%CI 1.097-1.413). The optimal critical value of peripheral blood ATX level at baseline for predicting HCC was 235.254 ng/ml, with the cut-off value of 0.714 in AUC of the ROC (95% CI was 0.597~ 0.857), sensitivity and specificity were 84.6% and 59.0%, respectively. Conclusion: ATX level was significantly higher in PBC patients over controls, and it's concentration was correlated with UDCA efficacy and fibrosis stage. ATX has potential values in predicting disease progression and PBC-related HCC.

Objective: To understand the dairy product intake in residents of Shanghai, its seasonal changes and the influencing factors. Methods: A group of representative residents was surveyed and followed up in four seasons in Shanghai during 2012-2014. Information of the dairy product intake was collected by food frequency questionnaire. Results: Liquid milk and yogurt were the main dairy products consumed by the residents of Shanghai. The annual dairy product intake rate was 41.8%, and the median of dairy intake of milk was 145.3 g/d, accounting for 48.4% of reference dietary intake value, and only 4.5% of people's diary product intake reached intake reference value. The area specific differences in intake rate of liquid milk, yogurt and total dairy product intake were significant in four seasons and in whole year (P<0.05). The area specific differences in total dairy product intake were significant (P<0.05) in spring, summer and winter. In general, it was shown that dairy product intake in urban area was higher than that in suburban area and in rural area. The data of Shanghai and urban area showed that the total dairy product intake was significant different among four seasons (P<0.05), but no significant difference was observed among four seasons in suburban and rural areas. The logistic regression analysis results showed that people with average household income higher than local average level or higher education levels were more likely to consume dairy products daily. People who reported to have good health status or sleep quality were more likely to drink milk compared to those who have worse health status or sleep quality (P<0.05). Conclusions: Even though dairy product intake rate and volume have been improved in residents in Shanghai, it is still stay at lower level, especially in rural area. To promote consumption of dairy products, it is necessary to control diary product price from macro perspective, and strengthen healthy education about the importance of dairy product intake and guide residents to select suitable dairy products.
Animals ; China ; Dairy Products ; Diet ; Humans ; Milk ; Seasons ; Surveys and Questionnaires

Objective: To assess the prevalence of blood donation and associated factors in men who have sex with men (MSM) in China. Methods: Our observational study was conducted between January and August, 2017 in 3 cities: Guangzhou, Shenzhen and Wuxi. Eligible participants were MSM (≥18 years old) who had either ≥2 male sex partners or unprotected anal sex with casual partners, or had been diagnosed with STI in the past 6 months. A self-completed tablet-based questionnaire was used to collect the information about MSM's socio-demographic characteristics, sexual behaviors and blood donation history. Results: A total of 603 MSM were enrolled in our study, including 302 in Guangzhou, 152 in Shenzhen and 149 in Wuxi, with a mean age of 27.9 years (SD=7.8). Overall, 29.2% (176/603) of the MSM reported a history of blood donation, and 33.1% (100/302)in Guangzhou, 27.6% (42/152) in Shenzhen and 22.8% (34/149) in Wuxi, the differences were not significant (χ(2)=6.421, P=0.093). Multivariate logistic regression analysis indicated that MSM had ever tested for HIV for ≥2 times in the past 12 months (vs. MSM tested for HIV one time, aOR=1.49, 95%CI: 1.08-2.19) or who had ever used gay dating app (vs. MSM who not used gay dating app, aOR=2.13, 95%CI: 1.12-4.44) were more likely to donate blood. Conclusions: Blood donation was common in MSM in China. Health education about blood donation in MSM should be strengthened to ensure the blood safety.
Adolescent ; Adult ; Blood Donors ; China ; Cities ; Cross-Sectional Studies ; Homosexuality, Male/statistics & numerical data* ; Humans ; Male ; Sexual Behavior ; Sexual Partners ; Surveys and Questionnaires

Objective: To analyze dietary pattern and its seasonal characteristic in residents of Shanghai. Methods: A representative sample was surveyed and followed up in four different seasons during 2012-2014. Information of food consumption was collected by 3-day 24-hour dietary recall and condiments weighing method. The intake of energy and macronutrients were calculated according to the Chinese Food Composition Table. Results: Annual average daily intake was 191.09 g for grain, 250.69 g for vegetable, 107.23 g for fruit, 223.53 g for animal food, 96.39 g for dairy products, 11.19 g for soy bean and its product, 36.54 g for cooking oil, and 7.57 g for salt. Significant differences were observed in food consumption among different seasons (P<0.05). Annual average daily intake of energy was 2 048.70 kcal, carbohydrates was 241.04 g, protein was 82.35 g, fat was 85.99 g and proportion of energy contributed by fat was 37.99%. Different seasons, age, residential areas, and income were influence factors for food consumption (P<0.05). Conclusions: Energy intake was adequate in residents of Shanghai. Unhealthy dietary pattern, including high proportion of fat and consumption of cooking oil and salt (lower than average intake of large cities, but higher than recommendation), was observed. It is necessary to take appropriate nutrition intervention, and future researches on dietary intake should consider seasonal influences.
China ; Cities ; Diet ; Energy Intake ; Feeding Behavior ; Humans ; Seasons

Shanghai Diet and Health Survey (SDHS) was designed to prospectively access local residents' food consumption, energy and nutrient intake, related chemical contaminant exposure, and the seasonal change trend to explore the relationship of diet with health. Data from SDHS can be used as fundamental information and scientific evidences for the development of local nutrition and food safety policies.
China ; Diet ; Energy Intake ; Health Surveys ; Nutrition Policy ; Nutrition Surveys