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BackgroundNumerous studies have reported on the associations between ambient temperatures and mortality. However, few multi-city studies have been conducted in developing countries including China. This study aimed to examine the association between high temperature and mortality outcomes in four cities with different climatic characteristics in China to identify the most vulnerable population, detect the threshold temperatures, and provide scientific evidence for public health policy implementations to respond to challenges from extreme heat.MethodsA semi-parametric generalized additive model (GAM) with a Poisson distribution was used to analyze the impacts of the daily maximum temperature over the threshold on mortality after controlling for covariates including time trends, day of the week (DOW), humidity, daily temperature range, and outdoor air pollution.ResultsThe temperature thresholds for all-cause mortality were 29°C, 35°C, 33°C and 34°C for Harbin, Nanjing, Shenzhen and Chongqing, respectively. After adjusting for potential confounders including air pollution, strong associations between daily maximum temperature and daily mortality from all-cause, cardiovascular, endocrine and metabolic outcomes, and particularly diabetes, were observed in different geographical cities, with increases of 3.2-5.5%, 4.6-7.5% and 12.5-31.9% (with 14.7-29.2% in diabetes), respectively, with each 1°C increment in the daily maximum temperature over the threshold. A stronger temperature-associated mortality was detected in females compared to males. Additionally, both the population over 55 years and younger adults aged 30 to 54 years reported significant heat-mortality associations.ConclusionsExtreme heat is becoming a huge threat to public health and human welfare due to the strong temperature-mortality associations in China. Climate change with increasing temperatures may make the situation worse. Relevant public health strategies and an early extreme weather and health warning system should be developed and improved at an early stage to prevent and reduce the health risks due to extreme weather and climate change in China, given its huge population, diverse geographic distribution and unbalanced socioeconomic status with various climatic characteristics.

Objective-S-Adenosylhomocysteine (SAH) is a better predictor of cardiovascular disease than homocysteine is, and it has been implicated in mediating the pathogenicity of hyperhomocysteinemia in atherosclerosis via an epigenetic mechanism. However, the underlying mechanism remains unclear. Here, we tested the hypothesis whether the effect of SAH on atherosclerosis is involved in epigenetic regulation of endoplasmic reticulum stress. Approach and Results-A total of 48 apolipoprotein E-deficient mice at 8 weeks were randomly divided into 4 groups (n=12 for each group). The control group was fed a conventional diet, the adenosine dialdehyde group was fed a diet that was supplemented with the SAH hydrolase inhibitor adenosine dialdehyde, and the other 2 groups were intravenously injected with a retrovirus that expressed either SAH hydrolase short hairpin RNA or scrambled short hairpin RNA semiweekly for 16 weeks. Plasma SAH levels and atherosclerotic lesion size were significantly increased in adenosine dialdehyde and SAH hydrolase short hairpin RNA groups when compared with control group. Expression of endoplasmic reticulum stress markers glucose-regulated protein-78 and CEBP-homologous protein was significantly increased in the mice with elevated plasma SAH levels. Moreover, plasma SAH was negatively associated with a decrease in the expression of trimethylated histone H3 lysine 9 and histone methyltransferases. Chromatin immunoprecipitation assays showed a significant decrease in trimethylated histone H3 lysine 9 occupancy at the glucose-regulated protein-78 and CEBP-homologous protein promoters in mice treated with adenosine dialdehyde and SAH hydrolase short hairpin RNA when compared with control mice. Conclusions-Our results suggest that elevated plasma SAH levels-accelerated atherosclerosis was associated with the activation of endoplasmic reticulum stress via modulation of histone methylation. Xiao et al SAH and Atherosclerosis 61factor 6 also plays a key role in the production of chaperones that facilitate the repair process, including glucose-regulated protein-78 (GRP78). Upregulation of PKR-like ER kinase increases the levels of activating transcription factor 4 and CEBP-homologous protein (CHOP), a potent inducer of apoptosis.12 Numerous studies have shown that homocysteine may promote atherosclerosis through the activation of ER stress.13,14 However, there is no direct evidence that homocysteine, and not SAH, is responsible for this effect on ER stress, and no precise mechanisms have been described.SAH is produced as a product of methylation reactions involving S-adenosylmethionine (SAM) as the methyl donor, including the methylation of DNA, histone, and other proteins. 15 The ratio of SAM/SAH has been frequently used as an indicator of the cellular methylation potential. 16 Histones can be methylated on either lysine (K) or arginine (R) residues. Lysine residues can be monomethylated, dimethylated, or trimethylated in vivo. It has been reported that trimethylated histone H3 K4 (3meH3K4) is strongly ass...

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