PURPOSE: The aim of this study was to characterize the demographics, usage patterns and complication rates of clomiphene use in male patients.MATERIALS AND METHODS: We retrospectively analyzed male patients from ages 20 to 55 years old who were prescribed clomiphene citrate from 2001 to 2014 using the Truven Health MarketScan, a US claims database. We collected data regarding associated medical diagnoses, diagnostic testing, duration of use, and reported side effects including thrombotic events, vision problems, gynecomastia, mental disorders, liver disease, nausea, or skin problems.RESULTS: In total, 12,318 men took clomiphene and represented the primary study cohort, with a mean age of 37.8 years. The percentage of men prescribed clomiphene increased over the study period, as did the average age of clomiphene users. Associated diagnoses included male infertility (52.0%), testicular hypofunction (13.5%), erectile dysfunction (2.4%), and low libido (0.4%). Associated testing included semen analysis (43.7%), testosterone (23.5%), luteinizing hormone (19.3%), and follicle-stimulating hormone (21.1%) levels. The median time of clomiphene use was 3.6 months, with 63% of men stopping within 6 months. No increased risk of reported clomiphene side effects were apparent in men taking the medication.CONCLUSIONS: There is a rising prevalence of clomiphene usage without associated adverse side effects in the US. The variability in associated diagnoses, diagnostic testing, and duration of use suggest a need for greater awareness of the proper evaluation and treatment of the men who are prescribed clomiphene.

Female ; Humans ; Endodermal Sinus Tumor/pathology* ; Adenocarcinoma/pathology* ; Choriocarcinoma/pathology*

Objective: To investigate the clinicopathological characteristics of esophageal carcinoma with gland duct differentiation. Methods: The clinical, morphologic and immunohistochemical (IHC) features of eight cases of esophageal carcinoma with gland duct differentiation diagnosed from 2012 to 2022 at the First Affiliated Hospital of Soochow University were summarized. Results: There were four males and four females, with a mean age of 68.5 (range 59-82) years. Two tumors were located in middle esophagus, five in the lower esophagus, and one in the cardia. The mean diameter was 2.4 cm (range 0.6-4.5 cm). The tumor had a bilayer epithelial structure, including the inner luminal epithelium and the outer basal epithelium. Immunohistochemistry showed that CK7 (8/8) and CK18 (8/8) were positive in the inner epithelium. p40 (8/8), p63 (8/8) and CK5/6 (8/8) were positive in the outer epithelium. SMA, calponin and CD117 were all negative. p53 mutants were found in all eight cases (strong and diffuse positivity in 6/8; complete loss of expression in 2/8). No columnar metaplasia, intestinal metaplasia and ectopic gastric mucosa were observed in the surface squamous epithelium in the cases. The mean follow-up time was 21.5 months (range 5-51 months). Seven patients survived and one patient died 31 months after surgery due to recurrence and liver metastasis. Conclusion: Esophageal carcinoma with esophageal gland duct differentiation is a rare tumor with unique histologic and IHC characteristics.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Esophageal Neoplasms/pathology* ; Epithelium/pathology* ; Metaplasia/metabolism* ; Carcinoma/pathology*

Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Cholangiocarcinoma/pathology* ; Carcinoma, Squamous Cell ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/pathology*

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

Precision medicine became the key strategy in development priority of science and technology in China. The large population-based cohorts become valuable resources in preventing and treating major diseases in the population, which can contribute scientific evidence for personalized treatment and precise prevention. The fundamental question of the achievements above, therefore, is how to construct a large population-based cohort in a standardized way. The Chinese Preventive Medicine Association co-ordinated experienced researchers from Peking University and other well-known institutes to write up two group standards Technical specification of data processing for large population-based cohort study (T/CPMA 001-2018) and Technical specification of data security for large population-based cohort study (T/CPMA 002-2018), on data management. The standards are drafted with principles of emphasizing their scientific, normative, feasible, and generalizable nature. In these two standards, the key principles are proposed, and technical specifications are recommended in data standardization, cleansing, quality control, data integration, data privacy protection, and database security and stability management in large cohort studies. The standards aim to guide the large population-based cohorts that have been or intended to be established in China, including national cohorts, regional population cohorts, and special population cohorts, hence, to improve domestic scientific research level and the international influence, and to support decision-making and practice of disease prevention and control.
China ; Cohort Studies ; Delivery of Health Care ; Humans ; Population Surveillance ; Quality Control ; Reference Standards

Objective: To understand the association between central obesity, assessed by waist circumference, and the risks for ischemic heart disease (IHD), major coronary event (MCE), and IHD death. Methods: After excluding participants with heart disease, stroke, cancer, COPD, and diabetes at baseline survey, we included a total of 428 595 participants from the China Kadoorie Biobank for the analysis. The baseline survey was conducted from June 2004 to July 2008. We used Cox proportional hazards model to estimate the hazard ratio (HR) and 95%CI. Results: During an average 9.1 years of follow-up (3 803 637 person-years), we documented 26 900 incident cases of IHD, 4 320 cases of MCE, and 2 787 of deaths from IHD. After adjustment for possible confounders and BMI, central obesity was found to be associated with increased risks for IHD, MCE, and IHD death. The adjusted HRs (for the participants who had waist circumference of 85.0-89.9 cm in men and 80.0-84.9 cm in women were 1.13 (95%CI: 1.09-1.17) for IHD, 1.15 (95%CI: 1.05-1.26) for MCE and 1.11 (95%CI: 0.98-1.24) for IHD death. The respective HRs for those central obese participants (men ≥90.0 cm, women ≥85.0 cm) were 1.29 (95%CI: 1.24-1.34), 1.30 (95%CI: 1.17-1.44) and 1.32 (95%CI: 1.16-1.51). Further stratification analysis according to BMI showed that the risks for incident IHD, MCE, and IHD death increased along with the increase of waist circumference even in the participants with normal weight. Conclusion: This large-scale prospective study revealed that central obesity was an independent risk factor for IHD in adults in China, and the risk of IHD would increase with the increase of waist circumference.
Adult ; Asian People/statistics & numerical data* ; Body Mass Index ; China/epidemiology* ; Female ; Heart Diseases/ethnology* ; Humans ; Male ; Obesity ; Obesity, Abdominal/epidemiology* ; Overweight/epidemiology* ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Waist Circumference

Objective: To describe the characteristics of cooking and heating fuel use in participants from the China Kadoorie Biobank (CKB) study. Methods: The CKB study recruited 512 891 adults from 10 areas in China during 2004-2008. Information on cooking fuel and heating fuel was collected using a questionnaire in baseline survey. The proportions of various fuels used in different areas, in different populations, and at different time points were calculated and compared. Results: Overall, 52.1% participants used solid fuel for cooking or heating. Rural areas had higher prevalence of solid fuel use than urban areas. The percentage of participants using solid fuel for cooking was 36.1% (coal 20.1%, wood/charcoal 16.0%); The percentage of participants using solid fuel for heating was 36.7% (coal 22.7%, wood/charcoal 14.0%). The prevalence of solid fuel use and the fuel type mainly used varied widely across 10 areas. The proportion of clean fuel use was lower in less-educated and lower-income people. Household coal and wood/charcoal use showed a declining trend, which was more remarkable in urban areas. Conclusion: There are still a large number of rural residents and people with low income relying on solid fuel in China, which is a serious public health concern.
Adult ; Air Pollution, Indoor ; China ; Coal ; Cooking ; Family Characteristics ; Humans ; Rural Population/statistics & numerical data* ; Urban Population/statistics & numerical data*

Objective: To study the relations between famine exposure and the risk of chronic diseases as diabetes mellitus, obesity, hypertension, coronary heart disease and stroke in the population of Harbin. Methods: Our data was collected from the baseline survey-the China Kadoorie Biobank project (CKB) in Harbin. Retrospective cohort study design was used. Related risks on chronic diseases including diabetes mellitus, obesity, hypertension, coronary heart disease and stroke, were compared among the famine exposed or non-exposed people, respectively by logistic analysis method. Results: After adjusted for factors as age, sex, physical activity, smoking, alcohol intake, diet, family history of diseases, it appeared that the factor 'famine exposure' had increased the risks of diseases as obesity (OR=1.204, 95%CI: 1.104-1.313, P<0.01), hypertension (OR=1.315, 95%CI: 1.210-1.429, P<0.01) and coronary heart disease (OR=1.495, 95%CI: 1.369-1.632, P<0.01). The lower the age of population being exposed to famine, the greater the risk of the development of all kinds of chronic diseases. Conclusions: Famine exposure appeared a risk factor for obesity, hypertension, and coronary heart disease. It is of great significance to ensure the life-long nutrition of the people, especially in the early and adolescent stages, to prevent obesity, hypertension, and coronary heart disease in their later lives.
Adolescent ; China/epidemiology* ; Chronic Disease/epidemiology* ; Coronary Disease/epidemiology* ; Diabetes Mellitus/epidemiology* ; Female ; Humans ; Hypertension/epidemiology* ; Obesity/epidemiology* ; Pregnancy ; Prenatal Exposure Delayed Effects/epidemiology* ; Retrospective Studies ; Socioeconomic Factors ; Starvation/epidemiology*