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: The aim of this study was to assess the risk factors and epidemiological characteristics of placental abruption (PA) in Hebei province. Methods: A cross-sectional survey was conducted to collect data on 218 880 pregnant women who were hospitalized in 22 hospitals which were under a monitoring program, in Hebei province, from January 1, 2013 to December 31, 2016. Data regarding epidemiological characteristics as time distribution, population distribution and related risk factors of placental abruption were gathered and analyzed. Results: In this cohort study, 218 880 women were included, with 669 (0.31%) of the pregnant women having PA. The overall prevalence rates were higher in the South than in the north parts of the area and higher in more developed regional economic centers. The average age of women having the episode was (27.87±4.50) years and presented "J" distribution on the prevalence of maternal age. Results from the multivariate regression analysis showed that the following factors were independently at risk for placental abruption: pregnancy the including hypertension (OR=1.65, 95%CI: 1.09-2.50), mild preeclampsia (OR=3.65, 95%CI: 2.40-5.56), severe preeclampsia (OR=4.72, 95%CI: 3.86-5.76) and anemia (OR=2.41, 95%CI: 2.05-2.83) which were all increased in pregnant women with PA compared with the normal female population without placental abruption. Conclusions: Placental abruption seemed to be associated with a moderate increasing risk of age, and was seen higher in those population older than 35 or younger than 20 year-olds. It was suggested that appropriate inoculation programs should be taken in different regions, especially on high-risk groups. Health education on related disease was of great significance for improving the prenatal outcome.
Abruptio Placentae/epidemiology* ; Adult ; China/epidemiology* ; Cohort Studies ; Cross-Sectional Studies ; Female ; Humans ; Hypertension ; Pre-Eclampsia/epidemiology* ; Pregnancy ; Retrospective Studies ; Risk Factors ; Young Adult

Humans ; Thyroid Cancer, Papillary ; Neck/pathology* ; Lymph Nodes/pathology* ; Thyroid Neoplasms/pathology* ; Lymphoma, T-Cell/pathology*

Objective: Based on data related to arsenic contents in paddy rice, as part of the food safety monitoring programs in 2017, to discuss and explore the application of spatial analysis used for food safety risk assessment. Methods: One province was chosen to study the spatial visualization, spatial point model estimation, and kernel density estimation. Moran's I statistic of spatial autocorrelation methods was used to analyze the spatial distribution at the county level. Results: Data concerning the spatial point model estimation showed that the spatial distribution of pollution appeared relatively dispersive. From the kernel density estimation, we found that the hot spots of pollution were mainly located in the central and eastern regions. The global Moran's I values appeared as 0.11 which presented low spatial aggregation to the rice arsenic contamination and with statistically significant differences. One "high-high" and two typical "low-low" clustering were seen in this study. Conclusion: Results from our study provided good visual demonstration, identification of pollution distribution rules, hot spots and aggregation areas for research on the distribution of food pollutants. Spatial statistics can provide technical support for the implementation of issue-based monitoring programs.
Arsenic/adverse effects* ; China ; Cluster Analysis ; Food Contamination ; Food Supply ; Humans ; Spatial Analysis

Objective: To know the situation of extramarital sexual behaviors and HIV infection in middle-aged and elderly people in Chongqing, and provide reference for AIDS prevention and treatment. Methods: From October to December 2017, a multi-stage sampling method was used to recruit middleaged and elderly people aged ≥50 years who lived in Dazu and Hechuan districts of Chongqing for at least one year, with a sample size of 410. Face-to-face questionnaires survey and HIV antibody test were conducted. Results: A total of 408 people were surveyed, including 313 males and 95 females aged 50-88 (64.93±9.03) years. The HIV infection rate was 1.47% (6/408), with the rate of 1.28% (4/313) in males and 2.11% (2/95) in females. The awareness rate of AIDS related knowledge was 37.50% (153/408). And 18.87% (77/408) of subjects surveyed reported extramarital sexual behaviors, 7.60% (31/408) reported extramarital sexual behaviors in the past half year, the constant condom use rate was 19.35% (6/31). The results of multivariate logistics model analysis on extramarital sexual behaviors showed that the prevalence in males were 39.51 times higher than that in females (OR=39.51, 95%CI: 5.03-310.30), 4.60 times higher in those who were unmarried, divorced or widowed than that in the married or cohabitants (OR=4.60, 95%CI: 1.50-14.05), 2.03 times higher in those with outside activities than those with individual activities (OR=2.03, 95%CI: 1.08-3.81) and 3.94 times higher in those with self-evaluation of emptiness of living state than that in those with engaged life (OR=3.94, 95%CI: 1.86-8.36). Conclusions: The prevalence of extramarital sexual behavior in middle-aged and elderly people in some counties and districts in Chongqing is high. The factors such as gender, marital status, leisure activities, and self-evaluation of living state were related to the prevalence of extramarital sexual behaviors in this population. The condom use rate in extramarital sexual behavior was low. It is necessary to take effective interventions in this population.
Aged ; Aged, 80 and over ; China/epidemiology* ; Condoms ; Extramarital Relations ; Female ; HIV Infections/transmission* ; Humans ; Male ; Marital Status ; Middle Aged ; Risk Factors ; Sexual Behavior ; Surveys and Questionnaires

Objective: To analyze the prevalence and co-prevalence of cardio-metabolic related risk factors in farmers aged ≥18 years in China, to explore the influence of population economic factors on them. Methods: A total of 3 367 farmers, including fishermen or hunters, aged ≥18 years were selected as study subjects from the database of Nutritional Status and Health Transition of Chinese Residents Project in 2015. Basic information (age, gender), data on anthropometric (body height, weight and waist size), blood biochemical and socioeconomic (occupation, income, education level and living area) were included. According to the definition of the metabolic syndrome released by the International Diabetes Federation (IDF) in 2005, five cardio-metabolic risk factors appeared as central obesity, increased triglycerides, decreased HDL-C, increased blood pressure and increased plasma glucose. Co-prevalence of risk factors was defined as detecting 2 or more risk factors in a person at the same time. Multivariate logistic regression model was used to analyze the relationship between socioeconomic factors and metabolic risk factors. Results: In 3 367 framers of 15 provinces (autonomous region and municipality), the prevalence rates of central obesity, increased blood pressure, increased plasma glucose, increased triglycerides and decreased HDL-C were 51.8%, 59.0%, 17.0%, 25.5% and 38.7% respectively. Multivariate logistic regression analysis showed that the risks for central obesity (OR=3.69, 95%CI: 3.17-4.28) and decreased HDL-C (OR=3.28, 95%CI: 2.81- 3.82) were higher in women than in men, and the risks for increased blood pressure (OR=0.73, 95%CI: 0.63-0.84), increased blood glucose (OR=0.80, 95%CI: 0.67-0.97) were lower in women than in men. Age was positively correlated with the prevalence or co-prevalence of metabolic risk factors (trend P<0.05). Framers in western China had obviously lower risk for central obesity compared with farmers in central China. No significant correlation was found between farmers' income level, education level or the prevalence of metabolic risk factors. Conclusion: In 15 provinces of China, the prevalence of at least 1 kind of cardio-metabolic risk factor was found in 85.5% of the farmers, and the co-prevalence of cardio-metabolic risk factor was found in 60% of farmers. The prevalence and co-prevalence of cardio-metabolic risk factors were significantly associated with age and gender. It is suggested to take targeted nutritional intervention and health education according to the distribution characteristics of prevalence and co-prevalence of cardio-metabolic factors and strengthen the early prevention and control programs of the diseases.
Adolescent ; Adult ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Farmers ; Female ; Humans ; Male ; Metabolic Syndrome/epidemiology* ; Obesity/epidemiology* ; Prevalence ; Risk Factors

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.
Adolescent ; Bayes Theorem ; Beijing ; Body Weight ; Child ; DNA Methylation/genetics* ; Epigenesis, Genetic ; Female ; Genome-Wide Association Study ; Humans ; Male ; Obesity/genetics* ; Twins, Monozygotic ; Waist Circumference

Objective: To describe the genetic structure of populations in different areas of China, and explore the effects of different strategies to control the confounding factors of the genetic structure in cohort studies. Methods: By using the genome-wide association study (GWAS) on data of 4 500 samples from 10 areas of the China Kadoorie Biobank (CKB), we performed principal components analysis to extract the first and second principal components of the samples for the component two-dimensional diagram generation, and then compared them with the source of sample area to analyze the characteristics of genetic structure of the samples from different areas of China. Based on the CKB cohort data, a simulation data set with cluster sample characteristics such as genetic structure differences and extensive kinship was generated; and the effects of different analysis strategies including traditional analysis scheme and mixed linear model on the inflation factor (λ) were evaluated. Results: There were significant genetic structure differences in different areas of China. Distribution of the principal components of the population genetic structure was basically consistent with the geographical distribution of the project area. The first principal component corresponds to the latitude of different areas, and the second principal component corresponds to the longitude of different areas. The generated simulation data showed high false positive rate (λ=1.16), even if the principal components of the genetic structure was adjusted or the area specific subgroup analysis was performed, λ could not be effectively controlled (λ>1.05); while, by using a mixed linear model adjusting for the kinship matrix, λ was effectively controlled regardless of whether the genetic structure principal component was further adjusted (λ=0.99). Conclusions: There were large differences in genetic structure among populations in different areas of China. In molecular epidemiology studies, bias caused by population genetic structure needs to be carefully treated. For large cohort data with complex genetic structure and extensive kinship, it is necessary to use a mixed linear model for association analysis.
China ; Genetic Structures ; Genome-Wide Association Study ; Humans ; Linear Models ; Principal Component Analysis

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective: To assess the association and intensity of baseline TC level with the incidence of lung cancer in men in China. Methods: Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history, anthropometry and TC level were collected at the baseline interview, as well as the information of newly-diagnosed lung cancer cases during the follow-up period. According to guidelines for blood lipids in Chinese adults and the distribution in the population, TC level was classified into five groups as followed: <160, 160-, 180-, 200- and ≥240 mg/dl, with the second quintile group (160- mg/dl) serving as the referent category. Cox proportional hazards regression model and restricted cubic spline (RCS) model were used to evaluate the association and the nonlinear association between baseline TC level and the risk of lung cancer in the men. Results: By December 31, 2014, for the 109 884 men, a follow up of 763 819.25 person-years was made with a median follow-up period of 7.88 years. During the follow up, 808 lung cancer cases were identified. After adjustment for age, education level, income level, smoking status, alcohol consumption level, history of dust exposure, FPG level and BMI, HR (95%CI) of lung cancer for men with lower TC level (<160 mg/dl) and higher TC level (≥240 mg/dl) were 1.34 (1.04- 1.72) and 1.45 (1.09-1.92), respectively, compared with men with normal TC level (160- mg/dl). The results didn't change significantly after exclusion of newly diagnosed cancer cases within 2 years of follow up and subjects with the history of hyperlipidemia. Conclusion: Our results showed that TC might be associated with higher risk of lung cancer. Men with lower TC level or higher TC level had higher risk for lung cancer. Keep moderate TC level might be one of the effective precaution for the prevention of lung cancer.
Adult ; Asian People ; China/epidemiology* ; Cholesterol/blood* ; Cohort Studies ; Humans ; Incidence ; Lipids ; Lung Neoplasms/ethnology* ; Male ; Proportional Hazards Models ; Prospective Studies ; Risk Factors