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AbstractObjectiveTo investigate the association between weight changes across adulthood and mortality.DesignProspective cohort study.SettingUS National Health and Nutrition Examination Survey (NHANES) 1988-94 and 1999-2014.Participants36 051 people aged 40 years or over with measured body weight and height at baseline and recalled weight at young adulthood (25 years old) and middle adulthood (10 years before baseline).Main outcome measuresAll cause and cause specific mortality from baseline until 31 December 2015.ResultsDuring a mean follow-up of 12.3 years, 10 500 deaths occurred. Compared with participants who remained at normal weight, those moving from the non-obese to obese category between young and middle adulthood had a 22% (hazard ratio 1.22, 95% confidence interval 1.11 to 1.33) and 49% (1.49, 1.21 to 1.83) higher risk of all cause mortality and heart disease mortality, respectively. Changing from obese to non-obese body mass index over this period was not significantly associated with mortality risk. An obese to non-obese weight change pattern from middle to late adulthood was associated with increased risk of all cause mortality (1.30, 1.16 to 1.45) and heart disease mortality (1.48, 1.14 to 1.92), whereas moving from the non-obese to obese category over this period was not significantly associated with mortality risk. Maintaining obesity across adulthood was consistently associated with increased risk of all cause mortality; the hazard ratio was 1.72 (1.52 to 1.95) from young to middle adulthood, 1.61 (1.41 to 1.84) from young to late adulthood, and 1.20 (1.09 to 1.32) from middle to late adulthood. Maximum overweight had a very modest or null association with mortality across adulthood. No significant associations were found between various weight change patterns and cancer mortality.ConclusionsStable obesity across adulthood, weight gain from young to middle adulthood, and weight loss from middle to late adulthood were associated with increased risks of mortality. The findings imply that maintaining normal weight across adulthood, especially preventing weight gain in early adulthood, is important for preventing premature deaths in later life.

The influence of overall lifestyle behaviors on diabetic microvascular complications remains unknown. In addition, the potential mediating biomarkers underlying the association is unclear. This study aimed to examine the associations of the combined lifestyle factors with risks of total and individual microvascular complications among patients with type 2 diabetes (T2D) and to explore the potential mediation effects of metabolic biomarkers. This retrospective cohort study included 15,104 patients with T2D free of macro- and microvascular complications at baseline (2006 to 2010) from the UK Biobank. Healthy lifestyle behaviors included noncurrent smoking, recommended waist circumference, regular physical activity, healthy diet, and moderate alcohol drinking. Outcomes were ascertained using electronic health records. Over a median of 8.1 years of follow-up, 1,296 cases of the composite microvascular complications occurred, including 558 diabetic retinopathy, 625 diabetic kidney disease, and 315 diabetic neuropathy, with some patients having 2 or 3 microvascular complications simultaneously. After multivariable adjustment for sociodemographic characteristics, history of hypertension, glycemic control, and medication histories, the hazard ratios (95% confidence intervals (CIs)) for the participants adhering 4 to 5 low-risk lifestyle behaviors versus 0 to 1 were 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite outcome (all Ps-trend ≤0.01). Further, the population-attributable fraction (95% CIs) of diabetic microvascular complications for poor adherence to the overall healthy lifestyle (<4 low-risk factors) ranged from 25.3% (10.0%, 39.4%) to 39.0% (17.7%, 56.8%). In addition, albumin, HDL-C, triglycerides, apolipoprotein A, C-reactive protein, and HbA1c collectively explained 23.20% (12.70%, 38.50%) of the associations between overall lifestyle behaviors and total diabetic microvascular complications. The key limitation of the current analysis was the potential underreporting of microvascular complications because the cases were identified via electronic health records. Adherence to overall healthy lifestyle behaviors was associated with a significantly lower risk of microvascular complications in patients with T2D, and the favorable associations were partially mediated through improving biomarkers of glycemic control, systemic inflammation, liver function, and lipid profile.

IntroductionUnhealthy lifestyles caused a huge disease burden. Adopting healthy lifestyles is the most cost-effective strategy for preventing non-communicable diseases. The aim was to perform a systematic review and meta-analysis to quantify the relationship of combined lifestyle factors (eg, cigarette smoking, alcohol consumption, physical activity, diet and overweight/obesity) with the risk of all-cause mortality, cardiovascular mortality and incident cardiovascular disease (CVD).MethodsPubMed and EMBASE were searched from inception to April 2019. Cohort studies investigating the association between the combination of at least three lifestyle factors and all-cause mortality, cardiovascular mortality or incidence of CVD were filtered by consensus among reviewers. Pairs of reviewers independently extracted data and evaluated study quality. Random-effects models were used to pool HRs. Heterogeneity and publication bias were tested.ResultsIn total, 142 studies were included. Compared with the participants with the least-healthy lifestyles, those with the healthiest lifestyles had lower risks of all-cause mortality (HR=0.45, 95% CI 0.41 to 0.48, 74 studies with 2 584 766 participants), cardiovascular mortality (HR=0.42, 95% CI 0.37 to 0.46, 41 studies with 1 743 530 participants), incident CVD (HR=0.38, 95% CI 0.29 to 0.51, 22 studies with 754 894 participants) and multiple subtypes of CVDs (HRs ranging from 0.29 to 0.45). The associations were largely significant and consistent among individuals from different continents, racial groups and socioeconomic backgrounds.ConclusionsGiven the great health benefits, comprehensively tackling multiple lifestyle risk factors should be the cornerstone for reducing the global disease burden.

In 2017, the 19th National Congress of the Communist Party of China put forward the concept of high-quality economic development, indicating that the Chinese economy has shifted from rapid growth to high-quality development. High-quality economic development is the growth mode of an innovation-driven economy, an innovative, high-efficiency, energy-saving, environmentally friendly, and high-value-added growth mode. Environmental regulation is an important means to solve economic development and environmental pollution and plays an important role in high-quality economic development. In order to explore the impact of China’s environmental regulations on the high-quality economic development, this paper based on the panel data of 30 provinces (cities) in China from 2004 to 2015 uses the dynamic spatial Dubin model (DSDM) to analyze the direct and indirect effects of China’s environmental regulations on high-quality economic development and regional heterogeneity. It also incorporates R&D (Research and Development) investment, government investment in environmental governance, and fiscal decentralization into the model and analyzes the direct and indirect effects of the above three factors in the process of environmental regulation affecting high-quality economic development. We found that China’s high-quality economic development is spatially related between different provinces. And environmental regulations have obvious direct and indirect effects in the impact of high-quality economic development in the central and eastern regions, and this effect phenomenon is not significant in the western region. R&D investment, environmental protection investment, and fiscal decentralization have different adjustment effects on environmental regulation and high-quality economic development, and the same kind of adjustment variable also shows obvious heterogeneity among different regions. Finally, we put forward relevant policy recommendations based on the conclusions, with a view to improving China’s high-quality economic development.

Background Cancer poses a huge disease burden, which could be reduced by adopting healthy lifestyles mainly composed of healthy diet, body weight, physical activity, limited alcohol consumption, and avoidance of smoking. However, no systematic review has summarised the relations of combined lifestyle factors with cancer morbidity and mortality. Methods EMBASE and PubMed were searched up to April 2019. Cohort studies investigating the association of combined lifestyle factors with risks of incident cancer and cancer mortality were selected. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias tests were conducted. Results The HRs (95% CIs) comparing individuals with the healthiest versus the least healthy lifestyles were 0.71 (0.66–0.76; 16 studies with 1.9 million participants) for incident cancer and 0.48 (0.42–0.54; 30 studies with 1.8 million participants) for cancer mortality. Adopting the healthiest lifestyles was also associated with 17 to 58% lower risks of bladder, breast, colon, endometrial, oesophageal, kidney, liver, lung, rectal, and gastric cancer. The relations were largely consistent and significant among participants with different characteristics in the subgroup analyses. Conclusions Adopting healthy lifestyles is associated with substantial risk reduction in cancer morbidity and mortality, and thus should be given priority for cancer prevention.

AbstractObjectiveTo estimate the global burden of type 2 diabetes in adolescents and young adults (aged 15-39 years) from 1990 to 2019.DesignSystematic analysis.Data sourceGlobal Burden of Disease Study 2019. Participants aged 15-39 years from 204 countries and territories, 1990-2019.Main outcomes measuresAge standardised incidence rate, age standardised disability adjusted life years (DALY) rate, and age standardised mortality rate for type 2 diabetes in people aged 15-39 years from 1990 to 2019, and proportional DALY attributable to different risk factors.ResultsFrom 1990 to 2019, significant increases in age standardised incidence rate and age standardised DALY rate were found for type 2 diabetes in adolescents and young adults globally (P<0.001). Age standardised incidence rate (per 100 000 population) increased from 117.22 (95% confidence interval 117.07 to 117.36) in 1990 to 183.36 (183.21 to 183.51) in 2019, and age standardised DALY rate (per 100 000 population) increased from 106.34 (106.20 to 106.48) in 1990 to 149.61 (149.47 to 149.75) in 2019. The age standardised mortality rate (per 100 000 population) was modestly increased from 0.74 (0.72 to 0.75) in 1990 to 0.77 (0.76 to 0.78) in 2019. When grouped by countries with different sociodemographic indexes, countries with a low-middle and middle sociodemographic index had the highest age standardised incidence rate and age standardised DALY rate in 2019, whereas countries with a low sociodemographic index had the lowest age standardised incidence rate but the highest age standardised mortality rate. Women generally had higher mortality and DALY rates than men at ages <30 years, but differences between the sexes were reversed in those aged >30 years except in countries with a low sociodemographic index. The main attributable risk factor for DALY for early onset type 2 diabetes was high body mass index in all regions by sociodemographic index. The proportional contribution of other risk factors varied across regions, however, with higher proportions of ambient particulate air pollution and smoking in countries with a high sociodemographic index and higher proportions of household air pollution from solid fuels and diet low in fruit in countries with a low sociodemographic index.ConclusionsEarly onset type 2 diabetes is a growing global health problem in adolescents and young adults, especially in countries with a low-middle and middle sociodemographic index. A greater disease burden in women aged <30 years was found. Specific measures are needed in countries with different levels of socioeconomic development because of the variable attributable risk factors for type 2 diabetes in adolescents and young adults.

The development of the digital economy is conducive to the innovative development of foreign trade and the formation of a “dual circulation” development pattern in China. Based on the panel data of 285 prefecture-level cities in China from 2005 to 2019, this paper examines the influence of the digital economy on urban export trade and its heterogeneity. And we use a mediating effect model to explore the possible mediating role of technological progress in the above influences. The results find that: (1) The improvement of the digital economy can promote cities export; (2) The promotion of the digital economy to the growth of city export scale is heterogeneous, which is more significant in the western and northeastern cities with relatively remote geographical locations, and the third-tier and lower cities with relatively backward economic development. (3) Technological progress has played a significant role in promoting the growth of export for the digital economy. Thus, it’s of great importance for China to increase investment in digital economy infrastructure and pay more attention to the differences in diverse city development processes. It should also support basic research and development in information technology to promote high-quality development of China’s foreign trade through the digital economy.

This study narrows its focus to the Yangtze River Delta, an important region in China known for its advancements in both digital economy and low-carbon technology. In contrast to previous studies, we also examine the heterogeneous effects between central and non-central cities, as well as the role of local financial development, when analyzing the impact of the digital economy on low-carbon innovation. Based on the data of 41 cities from 2011 to 2019, we find a significant direct promoting effect of the digital economy on low-carbon innovation. Furthermore, the development of the digital economy indirectly enhances low-carbon innovation through local financial development. The heterogeneous analysis reveals a positive impact of the digital economy on low-carbon innovation in both central and non-central cities, with a stronger effect observed in non-central cities. These findings suggest several policy recommendations, including promoting digital economy and finance, green finance, and fostering regional integration in the Yangtze River Delta.

Clinical therapy of doxorubicin (DOX) is limited due to its cardiotoxicity. miR-146a was proved as a protective factor in many cardiovascular diseases, but its role in chronic DOX-induced cardiotoxicity is unclear. The objective of this study was to demonstrate the role of miR-146a in low-dose long-term DOX-induced cardiotoxicity. Experiments have shown that DOX intervention caused a dose-dependent and time-dependent cardiotoxicity involving the increased of apoptosis and dysregulation of autophagy. The cardiotoxicity was inhibited by overexpressed miR-146a and was more severe when miR-146a was downgraded. Further research proved that miR-146a targeted TATA-binding protein (TBP) associated factor 9b (TAF9b), a coactivator and stabilizer of P53, indirectly destroyed the stability of P53, thereby inhibiting apoptosis and improving autophagy in cardiomyocytes. Besides, miR-146a knockout mice were used for in vivo validation. In the DOX-induced model, miR-146a deficiency made it worse whether in cardiac function, cardiomyocyte apoptosis or basal level of autophagy, than wild-type. In conclusion, miR-146a partially reversed the DOX-induced cardiotoxicity by targeting TAF9b/P53 pathway to attenuate apoptosis and adjust autophagy levels.

G protein-coupled receptors (GPCRs) are a large diverse family of cell surface signaling receptors implicated in various types of cancers. Several studies indicate that GPCRs control many aspects of cancer progression including tumor growth, invasion, migration, survival and metastasis. While it is known that GPCR activity can be altered in cancer through aberrant overexpression, gain-of-function activating mutations, and increased production and secretion of agonists, the precise mechanisms of how GPCRs contribute to cancer progression remains elusive. Protease-activated receptors (PARs) are a unique class of GPCRs implicated in cancer. PARs are a subfamily of GPCRs comprised of four members that are irreversibly activated by proteolytic cleavage induced by various proteases generated in the tumor microenvironment. Given the unusual proteolytic irreversible activation of PARs, expression of receptors at the cell surface is a key feature that influences signaling responses and is exquisitely controlled by endocytic adaptor proteins. Here, we discuss new survey data from the Cancer Genome Atlas and the Genotype-Tissue Expression projects analysis of expression of all PAR family member expression in human tumor samples as well as the role and function of the endocytic sorting machinery that controls PAR expression and signaling of PARs in normal cells and in cancer.