BACKGROUNDEpidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density (BMD) in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health.

METHODSSix-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used. Animals of each model were randomly assigned to the following four groups: Group 1, SHAM operated+vehicle; Group 2, orchidectomy (ORX)+vehicle; Group 3, ORX+low-dose losartan (10 mg×kg(-1)×d(-1)); and Group 4, ORX+high-dose losartan (25 mg×kg(-1)×d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily losartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test.

RESULTSUrine deoxypyridinoline/urine creatinine (DPD/Cr) ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose losartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose losartan, losartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY.

CONCLUSIONAngiotensin II type I receptor blocker losartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; pathology ; Hypertension ; drug therapy ; pathology ; physiopathology ; Losartan ; therapeutic use ; Male ; Orchiectomy ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole ; drug effects

Bovine theileriosis is a tick-borne disease that is hampering the development of the domestic cattle industry in northern China. This study involved a molecular survey of bovine Theileria species in 137 blood samples from cattle in the Jilin province of China. The DNA samples were screened by species-specific 18S rRNA PCR. Results revealed that 19.7% (27/137), 17.5% (24/137) and 10.9% (15/137) were found to be infected with Theileria sinensis, Theileria orientalis, respectively. Mixed infection was found in 8.8% (12/137). The overall detection rates of Baishan, Yanji, Jilin and Liaoyuan districts was 60.0%, 17.5%, 5.3% and 0%, respectively. There is little information on the detection and distribution of bovine Theileria species in northern China. Therefore, this study provides important data for understanding the epidemiology of Theileria species and designing appropriate approaches for the diagnosis and control of bovine theileriosis in northern China.

Objective: To identify the spatial clustering and its temporal trends among newly detected female HIV/AIDS cases aged 15 years or older, in China from 2010 to 2016. Methods: Newly detected HIV/AIDS cases among aged 15 years or older women in China during 2010-2016 were collected, to describe their demographic characteristics, changing trends and spatial autocorrelation. This program was conducted at county level, using the ArcGIS 10.3. Results: The number of newly detected HIV/AIDS cases among aged 15 years or older women was increasing annually from 16 603 to 26 196 in 2010 and in 2016. As the main route proportion of heterosexual transmission increased from 84.25% (13 988/16 603) in 2010 to 96.29%(25 224/26 196) in 2016. Both the number and proportion of HIV/AIDS cases among elderly women ≥50 years of age increased significantly from 17.82%(2 959/16 603) to 38.10%(9 981/26 196) in 2016. Results from spatial analysis demonstrated a county-level clustered distribution of HIV/AIDS cases across the country with a rising global Moran's I value=0.55 over the years (Z=51.46, P<0.001), which was concentrating on western and southern China, covering 9 provinces/autonomous regions/municipalities (Yunnan, Guangxi, Sichuan, Xinjiang, Guizhou, Guangdong, Chongqing, Henan and Hunan). The temporal trends of hot spots differed by age groups, with the trend of epidemic shifting towards western border and southern coastal regions among women aged 15-49 years old, while the elderly women aged ≥50 years old were spreading northward from the southwestern regions. Conclusion: Our findings indicated that an increasing trend of clusters appeared on HIV epidemic among newly detected female HIV/AIDS cases aged 15 years or older in China, particularly in the western and southern regions. Prevention and intervention strategies should target on women according to their age distribution, particularly in regions with increasing trend of HIV epidemics.
Adolescent ; Adult ; Age Distribution ; Aged ; China/epidemiology* ; Epidemics ; Female ; HIV Infections/ethnology* ; Humans ; Middle Aged ; Spatial Analysis ; Young Adult

Objective: To investigate the clinicopathological features and treatment of gastric alpha-fetoprotein (AFP)-producing adenocarcinoma with SWI/SNF complex deletion. Methods: Four cases of gastric AFP-producing adenocarcinoma with SWI/SNF complex deletion diagnosed in Zhongshan Hospital of Fudan University from January 2021 to December 2022 were collected, and their histomorphological characteristics, immunohistochemical (IHC), in situ hybridization of Epstein-Barr virus-encoded RNA (EBER), next-generation sequencing results, clinicopathological features and treatment were summarized, and literature review was conducted. Results: Among the 4 patients, there were three males and one female. They presented with abdominal pain, belching and melena. Serum AFP was significantly elevated in three patients, and endoscopy showed ulcerative lesions. Microscopically, the tumor cells showed mainly diffuse flaky or nest-like growth and typical characteristics of hepatoid adenocarcinoma. In two cases there were adenoid growth, and the tumor cells in these areas possessed clear cytoplasm, suggesting enteroblastic differentiation. The tumor cell nuclei were pleomorphic with large nucleoli and brisk mitoses. The IHC results showed that the tumor cells expressed AFP, GPC3 and SALL4, and there was retained expression of broad-spectrum keratin (CKpan) and E-cadherin. IHC detection of SWI/SNF complex subunits, namely INI1 (SMARCB1), BRG1 (SMARCA4), BRM (SMARCA2), ARID1A protein was performed. In all four cases the hepatoid adenocarcinoma region and enteroblastic differentiation region showed SMARCA2 deletion, and one case with enteroblastic differentiation also showed ARID1A deletion. SMARCB1 and SMARCA4 deletions were not seen. All the four cases were diffusely positive for p53 protein, and the Ki-67 proliferation index was 80%-90%. There were no mismatch repair deletion detected; one cases showed HER2 was strongly positive (3+), and EBER was negative. None of the four cases had mutations in the SWI/SNF complex-related subunits detected by next-generation sequencing. Among the four patients, two underwent palliative surgery due to distant metastasis at the time of surgery, two underwent radical resection. Postoperative adjuvant chemotherapy was given to three patients. Conclusions: AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.
Male ; Humans ; Female ; alpha-Fetoproteins ; Stomach Neoplasms/genetics* ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Adenocarcinoma/pathology* ; Biomarkers, Tumor/genetics* ; DNA Helicases/genetics* ; Nuclear Proteins ; Transcription Factors/genetics* ; Glypicans

Objective: To understand the rate on tobacco use and associated factors in junior middle school students in Shaanxi province. Methods: We used a multi-stage stratified random sampling method to select students from 30 junior middle schools in 10 areas of Shaanxi province in 2013. All the participants completed a self-administered questionnaire. Results: A total of 4 633 questionnaires were dispatched and 4 298 were qualified for further analysis. The current smoking rate of junior middle school students in Shaanxi was 6.5%, with rate in male (11.1%) higher than that of female students (1.7%). The current smoking rate of students in grade three (9.3%) was higher than those of students in grade one (3.5%) or in grade two (7.0%). The smoking rate of students with pocket money more than 31 Yuan per week was (10.0%) higher than those of students with pocket money less than 10 Yuan (4.6%) or 10-30 Yuan (6.3%) per week. Results from the logistic regression analysis showed that factors as: male, school located in the city, older age, with more pocket money, having smokers in the family and exposure to second hand smoking were high risk factors for current smoking. Conclusion: Rate on current smoking was high in junior middle schools students in Shaanxi, suggesting that comprehensive intervention programs be developed to reduce the rate of tobacco use in junior middle school students.
China/epidemiology* ; Cities ; Cross-Sectional Studies ; Female ; Humans ; Male ; Prevalence ; Schools ; Smoking/epidemiology* ; Students/statistics & numerical data* ; Surveys and Questionnaires ; Tobacco Smoke Pollution/adverse effects* ; Tobacco Use/epidemiology*

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