Pregnancy ; Female ; Humans ; Mucolipidoses ; Placenta

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 establish a dynamic compartmental model to predict the impact of HIV testing and treatment and pre-exposure prophylaxis (PrEP) on the annual incidence of HIV infection in men who have sex with men (MSM) in China from 2018 to 2037. Methods: A dynamic compartmental model was developed to describe the HIV epidemic in MSM in China. The model was parameterized using data from the literature available. We used MATLAB 7.0 software for data simulation and graphics rendering. We analyzed HIV transmission among MSM and estimated the impact of expanded HIV testing and treatment and PrEP on HIV elimination in MSM. Results: Under the current policy, the number of new HIV infections would reach 770 000, the infection rate would reach 11.1% and the incidence rate would reach 0.72/100 person years in MSM in the next 20 years. Under the 90%-90%-90% goal, 440 000 new infections (57.7%) would be reduced, the HIV infection rate would decline to 5.7% and the incidence rate would decline to 0.24/100 person years in the next 20 years, but it is still unlikely to achieve the goal of HIV elimination. With 100% PrEP compliance, the required PrEP coverage rates for achieving HIV elimination in the next 10, 15 and 20 years would be 65%, 32% and 19%, respectively. Conclusion: It is necessary to strengthen the comprehensive intervention in MSM, continue to expand HIV testing and treatment, and improve PrEP adherence and coverage to further control and eliminate the epidemic of HIV/AIDS in MSM.
China ; Goals ; HIV ; HIV Infections/transmission* ; Homosexuality, Male ; Humans ; Male ; Models, Theoretical ; Pre-Exposure Prophylaxis

Hearing Loss, High-Frequency ; Hearing Loss, Noise-Induced/epidemiology* ; Humans ; Manufacturing Industry ; Noise, Occupational/adverse effects* ; Occupational Exposure

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

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