[Overexpression of human EP4 receptor in vascular smooth muscle cells attenuates angiotensin II-induced hypertension in mice].

Prostaglandin E2 (PGE2) plays an important role in cardiovascular system. PGE2 regulates blood pressure through its 4 G protein coupled receptors, i.e., EP1, EP2, EP3, and EP4. The aim of this study was to investigate the role of EP4 receptors in vascular smooth muscle cells (VSMC) in blood pressure regulation. VSMC-specific human EP4 transgenic (VSMC-hEP4 Tg) mice were generated and genotyped. The systolic blood pressure (SBP) of the VSMC-hEP4 Tg mice and the wild-type (WT) littermates was measured under normal, low-salt (LSD) and high-salt diet (HSD) conditions using a tail-cuff method. Both WT and VSMC-hEP4 Tg mice were administered with a chronic infusion of angiotensin II (Ang II) with an osmotic pump and SBP levels were monitored every week. The mean arterial blood pressure (MAP) of WT and VSMC-hEP4 Tg mice upon Ang II intravenous infusion was measured via carotid arterial catheterization. Ang II-induced vasoconstriction of the mesenteric arterial rings from WT and VSMC-hEP4 Tg mice was measured using the multi myograph system. The effect of PGE1-OH (a selective EP4 agonist) on Ang II-induced phosphorylation of myosin phosphatase target subunit 1 (MYPT1) was detected by Western blot. The effect of two additional EP4 specific agonists (CAY10580 and CAY10598, 0.5 mg/kg) on blood pressure of WT mice was measured by carotid arterial catheterization. The results showed that the VSMC-hEP4 Tg mice were successfully generated and their basal SBP levels were lower than those of WT mice. Although blood pressure levels were significantly altered in WT mice under LSD and HSD, little change was observed in the VSMC-hEP4 Tg mice. After a chronic infusion and an acute intravenous injection of Ang II, SBP levels of VSMC-hEP4 Tg mice were significantly lower than those of WT mice. In addition, both CAY10580 and CAY10598 significantly reduced MAP levels of WT mice. Ex vivo study showed that treatment of isolated mesenteric arteries with PGE1-OH inhibited Ang II-induced phosphorylation of MYPT1. Collectively, these results demonstrate that specific overexpression of human EP4 gene in VSMCs significantly reduces basal blood pressure levels and attenuates Ang II-induced hypertension, possibly via inhibiting Ang II/AT1 signaling pathway. Our findings suggest that EP4 may represent an attractive target for the treatment of hypertension.

Regression-based normative data for social health scale for the elderly (short version) in eastern China.

BACKGROUNDS: Social Health Scale for the Elderly short version (SHSE-S) is a psychometrically sound instrument that comprehensively assesses the social health status of older adults in China. The aim of the present study was to establish continuous normative data of SHSE-S. METHODS: We conducted a multicenter cross-sectional study among 31 communities in eastern China. Older adults aged 60 years and above were invited to participate in the study. Each participant was interviewed in-person to finish a structured questionnaire. The SHES-S score was calculated and standardized for each participant. We split the sample into generation and validation datasets and compared the distribution of SHSE-S score between two datasets. Multivariable linear regression was used to assess the SHSE-S score and demographic variables. Regression-based norms were built using a four-step process. RESULTS: A total of 6089 participants (51.2% females) aged 60 years old and above (mean age = 71.3, SD = 8.0) were enrolled as the normative sample. No significant difference was found between the distribution of SHSE-S standardized score in the generation (N = 2392) and validation (N = 3697) datasets. Multivariable linear regression showed that females, higher education levels were positive indicators while aging, living alone, divorced or never married, multimorbidity were negative factors. The regression-based norm which taking demographic factors into account was established and a user-friendly worksheet was also provided to facilitate the scoring and norming of the SHSE-S. CONCLUSIONS: The population-based regression norm of SHSE-S can be a useful tool for assessing the social health status of the Chinese elderly population.

Attributable causes of colorectal cancer in China.

BACKGROUND: Colorectal cancer is the 4th common cancer in China. Most colorectal cancers are due to modifiable lifestyle factors, but few studies have provided a systematic evidence-based assessment of the burden of colorectal cancer incidence and mortality attributable to the known risk factors in China. METHODS: We estimated the population attributable faction (PAF) for each selected risk factor in China, based on the prevalence of exposure around 2000 and relative risks from cohort studies and meta-analyses. RESULTS: Among 245,000 new cases and 139,000 deaths of colorectal cancer in China in 2012, we found that 115,578 incident cases and 63,102 deaths of colorectal cancer were attributable to smoking, alcohol drinking, overweight and obesity, physical inactivity and dietary factors. Low vegetable intake was the main risk factor for colorectal cancer with a PAF of 17.9%. Physical inactivity was responsible for 8.9% of colorectal cancer incidence and mortality. The remaining factors, including high red and processed meat intake, low fruit intake, alcohol drinking, overweight/obesity and smoking, accounted for 8.6%, 6.4%, 5.4%, 5.3% and 4.9% of colorectal cancer, respectively. Overall, 45.5% of colorectal cancer incidence and mortality were attributable to the joint effects of these seven risk factors. CONCLUSIONS: Tobacco smoking, alcohol drinking, overweight or obesity, physical inactivity, low vegetable intake, low fruit intake, and high red and processed meat intake were responsible for nearly 46% of colorectal cancer incidence and mortality in China in 2012. Our findings could provide a basis for developing guidelines of colorectal cancer prevention and control in China.