Paraspeckle protein NONO attenuates vascular calcification by inhibiting bone morphogenetic protein 2 transcription.

Vascular calcification is a pathological process commonly associated with atherosclerosis, chronic kidney disease, and diabetes. Paraspeckle protein NONO is a multifunctional RNA/DNA binding protein involved in many nuclear biological processes but its role in vascular calcification remains unclear. Here, we observed that NONO expression was decreased in calcified arteries of mice and patients with CKD. We generated smooth muscle-specific NONO-knockout mice and established three different mouse models of vascular calcification by means of 5/6 nephrectomy, adenine diet to induce chronic kidney failure, or vitamin D injection. The knockout mice were more susceptible to the development of vascular calcification relative to control mice, as verified by an increased calcification severity and calcium deposition. Likewise, aortic rings from knockout mice showed more significant vascular calcification than those from control mice ex vivo. In vitro, NONO deficiency aggravated high phosphate-induced vascular smooth muscle cell osteogenic differentiation and apoptosis, whereas NONO overexpression had a protective effect. Mechanistically, we demonstrated that the regulation of vascular calcification by NONO was mediated by bone morphogenetic protein 2 (BMP2). NONO directly bound to the BMP2 promoter using its C-terminal region, exerting an inhibitory effect on the transcription of BMP2. Thus, our study reveals that NONO is a novel negative regulator of vascular calcification, which inhibits osteogenic differentiation of vascular smooth muscle cell and vascular calcification via negatively regulating BMP2 transcription. Hence, NONO may provide a promising target for the prevention and treatment of vascular calcification.

A proposed simplified definition of metabolic syndrome in children and adolescents: a global perspective.

Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice.We proposed a simplified definition for assessing MetS risk in youths aged 6-17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89-0.92) and 0.79 (0.78-0.81) when using the IDF or NCEP definition as the gold standard, respectively.The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally.

Pediatric Blood Pressure and Cardiovascular Health in Adulthood.

PURPOSE OF REVIEW: This review summarizes current knowledge on blood pressure in children and adolescents (youth), with a focus on primary hypertension-the most common form of elevated blood pressure in this demographic. We examine its etiology, progression, and long-term cardiovascular implications. The review covers definitions and recommendations of blood pressure classifications, recent developments in measurement, epidemiological trends, findings from observational and clinical studies, and prevention and treatment, while identifying gaps in understanding and suggesting future research directions. RECENT FINDINGS: Youth hypertension is an escalating global issue, with regional and national variations in prevalence. While the principles of blood pressure measurement have remained largely consistent, challenges in this age group include a scarcity of automated devices that have passed independent validation for accuracy and a generally limited tolerance for ambulatory blood pressure monitoring. A multifaceted interplay of factors contributes to youth hypertension, impacting long-term cardiovascular health. Recent studies, including meta-analysis and sophisticated life-course modelling, reveal an adverse link between youth and life-course blood pressure and subclinical cardiovascular outcomes later in life. New evidence now provides the strongest evidence yet linking youth blood pressure with clinical cardiovascular events in adulthood. Some clinical trials have expanded our understanding of the safety and efficacy of antihypertensive medications in youth, but this remains an area that requires additional attention, particularly regarding varied screening approaches. This review outlines the potential role of preventing and managing blood pressure in youth to reduce future cardiovascular risk. A global perspective is necessary in formulating blood pressure definitions and strategies, considering the specific needs and circumstances in low- and middle-income countries compared to high-income countries.

METTL3 (Methyltransferase Like 3)-Dependent N6-Methyladenosine Modification on Braf mRNA Promotes Macrophage Inflammatory Response and Atherosclerosis in Mice.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease, in which macrophages determine the progression of atherosclerotic plaques. However, no studies have investigated how METTL3 (methyltransferase like 3) in macrophages affects atherosclerotic plaque formation in vivo. Additionally, whether Braf mRNA is modified by METTL3-dependent N6-methyladenosine (m6A) methylation remains unknown. METHODS: We analyzed single-cell sequencing data of atherosclerotic plaques in mice fed with a high fat diet for different periods. Mettl3fl/fl Lyz2cre Apoe-/- mice and littermate control Mettl3fl/fl Apoe-/- mice were generated and fed high fat diet for 14 weeks. In vitro, we stimulated peritoneal macrophages with ox-LDL (oxidized low-density lipoprotein) and tested the mRNA and protein expression levels of inflammatory factors and molecules regulating ERK (extracellular signal-regulated kinase) phosphorylation. To find METTL3 targets in macrophages, we performed m6A-methylated RNA immunoprecipitation sequencing and m6A-methylated RNA immunoprecipitation-qPCR. Further, point mutation experiments were used to explore m6A-methylated adenine. Using RNA immunoprecipitation assay, we explored m6A methylation-writing protein bound to Braf mRNA. RESULTS: In vivo, METTL3 expression in macrophages increased with the progression of atherosclerosis. Myeloid cell-specific METTL3 deletion negatively regulated atherosclerosis progression and the inflammatory response. In vitro, METTL3 knockdown or knockout in macrophages attenuated ox-LDL-mediated ERK phosphorylation rather than JNK (c-Jun N-terminal kinase) and p38 phosphorylation and reduced the level of inflammatory factors by affecting BRAF protein expression. The negative regulation of inflammation response caused by METTL3 knockout was rescued by overexpression of BRAF. In mechanism, METTL3 targeted adenine (39725126 in chromosome 6) on the Braf mRNA. Then, YTHDF1 could bind to m6A-methylated Braf mRNA and promoted its translation. CONCLUSIONS: Myeloid cell-specific Mettl3 deficiency suppressed hyperlipidemia-induced atherosclerotic plaque formation and attenuated atherosclerotic inflammation. We identified Braf mRNA as a novel target of METTL3 in the activation of the ox-LDL-induced ERK pathway and inflammatory response in macrophages. METTL3 may represent a potential target for the treatment of atherosclerosis.

How spin state and oxidation number of transition metal atoms determine molecular adsorption: a first-principles case study for NH3.

Understanding how the electronic state of transition metal atoms can influence molecular adsorption on a substrate is of great importance for many applications. Choosing NH3 as a model molecule, its adsorption behavior on defected SnS2 monolayers is investigated. The number of valence electrons n is controlled by decorating the monolayer with different transition metal atoms, ranging from Sc to Zn. Density-Functional Theory based calculations show that the adsorption energy of NH3 molecules oscillates with n and shows a clear odd-even pattern. There is also a mirror symmetry of the adsorption energies for large and low electron numbers. This unique behavior is mainly governed by the oxidation state of the TM ions. We trace back the observed trends of the adsorption energy to the orbital symmetries and ligand effects which affect the interaction between the 3σ orbitals (NH3) and the 3d orbitals of the transition metals. This result unravels the role which the spin state of TM ions plays in different crystal fields for the adsorption behavior of molecules. This new understanding of the role of the electronic structure on molecular adsorption can be useful for the design of high efficiency nanodevices in areas such as sensing and photocatalysis.

A systematic review of qualitative research on the self-management experience of breast cancer patients.

OBJECTIVE: To integrate the qualitative research on the self-management experience of breast cancer patients and conduct a systematic review of their self-management experience. METHODS: Using a computer to search a series of databases such as CNKI, Wanfang, VIP, and China Biomedical Database, systematically collect and integrate qualitative research on the self-management experience of breast cancer patients, and the search time is limited to January 2010 to December 2022. The qualitative research quality evaluation standard of the Joanna Briggs Institute Centre for Evidence-Based Health Care in Australia was used as the evaluation standard of this project to complete the accurate evaluation of the literature; Meta-analysis was used to complete the effective integration of the results. RESULTS: 17 pieces of literature were included in this project, and 37 research results with strong integrity were extracted accordingly. On this basis, 7 different categories were summarised, and three integrated results were obtained: the experience of maintaining self-management, symptom recognition, and self-management. CONCLUSION: In the different stages of self-management of breast cancer patients, medical staff should give targeted guidance to help patients obtain a good prognosis.

Global, regional, and national burden of cardiovascular diseases in youths and young adults aged 15-39 years in 204 countries/territories, 1990-2019: a systematic analysis of Global Burden of Disease Study 2019.

BACKGROUND: Understanding the temporal trends in the burden of overall and type-specific cardiovascular diseases (CVDs) in youths and young adults and its attributable risk factors is important for effective and targeted prevention strategies and measures. We aimed to provide a standardized and comprehensive estimation of the prevalence, incidence, disability-adjusted life years (DALY), and mortality rate of CVDs and its associated risk factors in youths and young adults aged 15-39 years at global, regional, and national levels. METHODS: We applied Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 analytical tools to calculate the age-standardized incidence, prevalence, DALY, and mortality rate of overall and type-specific CVDs (i.e., rheumatic heart disease, ischemic heart disease, stroke, hypertensive heart disease, non-rheumatic valvular heart disease, cardiomyopathy and myocarditis, atrial fibrillation and flutter, aortic aneurysm, and endocarditis) among youths and young adults aged 15-39 years by age, sex, region, sociodemographic index and across 204 countries/territories from 1990 to 2019, and proportional DALY of CVDs attributable to associated risk factors. RESULTS: The global age-standardized DALY (per 100,000 population) for CVDs in youths and young adults significantly decreased from 1257.51 (95% confidence interval 1257.03, 1257.99) in 1990 to 990.64 (990.28, 990.99) in 2019 with an average annual percent change (AAPC) of - 0.81% (- 1.04%, - 0.58%, P < 0.001), and the age-standardized mortality rate also significantly decreased from 19.83 (19.77, 19.89) to 15.12 (15.08, 15.16) with an AAPC of - 0.93% (- 1.21%, - 0.66%, P < 0.001). However, the global age-standardized incidence rate (per 100,000 population) moderately increased from 126.80 (126.65, 126.95) in 1990 to 129.85 (129.72, 129.98) in 2019 with an AAPC of 0.08% (0.00%, 0.16%, P = 0.040), and the age-standardized prevalence rate significantly increased from 1477.54 (1477.03, 1478.06) to 1645.32 (1644.86, 1645.78) with an AAPC of 0.38% (0.35%, 0.40%, P < 0.001). In terms of type-specific CVDs, the age-standardized incidence and prevalence rate in rheumatic heart disease, prevalence rate in ischemic heart disease, and incidence rate in endocarditis increased from 1990 to 2019 (all P < 0.001). When stratified by sociodemographic index (SDI), the countries/territories with low and low-middle SDI had a higher burden of CVDs than the countries/territories with high and high-middle SDI. Women had a higher prevalence rate of CVDs than men, whereas men had a higher DALY and mortality rate than women. High systolic blood pressure, high body mass index, and low-density lipoprotein cholesterol were the main attributable risk factors for DALY of CVDs for all included countries and territories. Household air pollution from solid fuels was an additional attributable risk factor for DALY of CVDs in low and low-middle SDI countries compared with middle, high-middle, and high SDI countries. Compared with women, DALY for CVDs in men was more likely to be affected by almost all risk factors, especially for smoking. CONCLUSIONS: There is a substantial global burden of CVDs in youths and young adults in 2019. The burden of overall and type-specific CVDs varied by age, sex, SDI, region, and country. CVDs in young people are largely preventable, which deserve more attention in the targeted implementation of effective primary prevention strategies and expansion of young-people's responsive healthcare systems.

Maternal hypertensive disorders during pregnancy and the risk of offspring diabetes mellitus in childhood, adolescence, and early adulthood: a nationwide population-based cohort study.

BACKGROUND: Maternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood. METHODS: Using Danish national health registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offspring's age as the time scale. RESULTS: During a follow-up of up to 41 (median: 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR=1.27, 95% CI=1.20-1.34), as well as for type 2 diabetes (HR=1.57, 95% CI=1.38-1.78) and gestational diabetes (HR=1.37, 95% CI=1.25-1.49). We did not observe obvious increased risk for type 1 diabetes (HR=1.08, 95% CI=0.98-1.18). Offspring of mothers with gestational hypertension (HR=1.37, 95% CI=1.00-1.88) or preeclampsia (HR=1.62, 95% CI=1.41-1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR=2.00, 95% CI=1.42-2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR=1.41, 95%CI=1.17-1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06-2.41), 1.29 (1.04-1.59), and 1.38 (1.24-1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR=4.64, 95%CI=3.85-5.60) than offspring of mothers with HDP or diabetes alone. CONCLUSIONS: Offspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations.

Association of the American Heart Association's new "Life's Essential 8" with all-cause and cardiovascular disease-specific mortality: prospective cohort study.

BACKGROUND: The American Heart Association recently updated its construct of what constitutes cardiovascular health (CVH), called Life's Essential 8. We examined the association of total and individual CVH metrics according to Life's Essential 8 with all-cause and cardiovascular disease (CVD)-specific mortality later in  life. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 at baseline linked to the 2019 National Death Index records. Total and individual CVH metric scores including diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure were classified as 0-49 (low level), 50-74 (intermediate level), and 75-100 (high level) points. The total CVH metric score (the average of the 8 metrics) as a continuous variable was also used for dose-response analysis. The main outcomes included all-cause and CVD-specific mortality. RESULTS: A total of 19,951 US adults aged 30-79 years were included in this study. Only 19.5% of adults achieved a high total CVH score, whereas 24.1% had a low score. During a median follow-up of 7.6 years, compared with adults with a low total CVH score, those with an intermediate or high total CVH score had 40% (adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.51-0.71) and 58% (adjusted HR 0.42, 95% CI 0.32-0.56) reduced risk of all-cause mortality. The corresponding adjusted HRs (95%CIs) were 0.62 (0.46-0.83) and 0.36 (0.21-0.59) for CVD-specific mortality. The population-attributable fractions for high (score ≥ 75 points) vs. low or intermediate (score < 75 points) CVH scores were 33.4% for all-cause mortality and 42.9% for CVD-specific mortality. Among all 8 individual CVH metrics, physical activity, nicotine exposure, and diet accounted for a large proportion of the population-attributable risks for all-cause mortality, whereas physical activity, blood pressure, and blood glucose accounted for a large proportion of CVD-specific mortality. There were approximately linear dose-response associations of total CVH score (as a continuous variable) with all-cause and CVD-specific mortality. CONCLUSIONS: Achieving a higher CVH score according to the new Life's Essential 8 was associated with a reduced risk of all-cause and CVD-specific mortality. Public health and healthcare efforts targeting the promotion of higher CVH scores could provide considerable benefits to reduce the mortality burden later in life.

Establishing international optimal cut-offs of waist-to-height ratio for predicting cardiometabolic risk in children and adolescents aged 6-18 years.

BACKGROUND: Waist-to-height ratio (WHtR) has been proposed as a simple and effective screening tool for assessing central obesity and cardiometabolic risk in both adult and pediatric populations. However, evidence suggests that the use of a uniform WHtR cut-off of 0.50 may not be universally optimal for pediatric populations globally. We aimed to determine the optimal cut-offs of WHtR in children and adolescents with increased cardiometabolic risk across different countries worldwide. METHODS: We used ten population-based cross-sectional data on 24,605 children and adolescents aged 6-18 years from Brazil, China, Greece, Iran, Italy, Korea, South Africa, Spain, the UK, and the USA for establishing optimal WHtR cut-offs. We performed an external independent test (9,619 children and adolescents aged 6-18 years who came from other six countries) to validate the optimal WHtR cut-offs based on the predicting performance for at least two or three cardiometabolic risk factors. RESULTS: Based on receiver operator characteristic curve analyses of various WHtR cut-offs to discriminate those with ≥ 2 cardiometabolic risk factors, the relatively optimal percentile cut-offs of WHtR in the normal weight subsample population in each country did not always coincide with a single fixed percentile, but varied from the 75th to 95th percentiles across the ten countries. However, these relatively optimal percentile values tended to cluster irrespective of sex, metabolic syndrome (MetS) criteria used, and WC measurement position. In general, using ≥ 2 cardiometabolic risk factors as the predictive outcome, the relatively optimal WHtR cut-off was around 0.50 in European and the US youths but was lower, around 0.46, in Asian, African, and South American youths. Secondary analyses that directly tested WHtR values ranging from 0.42 to 0.56 at 0.01 increments largely confirmed the results of the main analyses. In addition, the proposed cut-offs of 0.50 and 0.46 for two specific pediatric populations, respectively, showed a good performance in predicting ≥ 2 or ≥ 3 cardiometabolic risk factors in external independent test populations from six countries (Brazil, China, Germany, Italy, Korea, and the USA). CONCLUSIONS: The proposed international WHtR cut-offs are easy and useful to identify central obesity and cardiometabolic risk in children and adolescents globally, thus allowing international comparison across populations.

Abdominal obesity-related lipid metabolites may mediate the association between obesity and glucose dysregulation.

BACKGROUND: Children with obesity is associated with a higher risk of cardiovascular disease (CV) risk in adulthood. This study is to explore the obesity-related lipid metabolites and identify the associations of lipid metabolites with selected CV risk in children and adolescents. METHODS: A case-control study was designed to include a total of 197 children (aged 9-13 years, male 56.34%, 99 children in the obesity group). The lipidomics profiling was measured by ultra-high-performance liquid tandem chromatography quadrupole time-of-flight mass spectrometry. RESULTS: Four FDR-significant abdominal obesity-related lipid metabolites were identified. Compared to the lean group, decreased phosphatidylcholine O-21:2 level (q = 0.010) and sphingomyelins d21:1 (q = 0.029) were found and two lipid metabolites levels were higher in the obese group, including phosphatidylglycerol 43:6 and one did not match with any candidate compounds in databases. After adjusting for covariates, PC3 (O-21:2) and SM (d21:1) were significantly associated with blood glucose. Mediation analysis showed that all three lipid metabolites may mediate the association between abdominal obesity and glucose regulation. CONCLUSIONS: This study identified several novel central obesity-related lipid metabolites, and we found that PC3 (O-21:2) and SM (d21:1) were significantly associated with blood glucose, and all these lipid metabolites can mediate the association between abdominal obesity and glucose dysregulation. IMPACT: Serum lipidomic profiles in children with abdominal obesity and their associations with selected CV risk factors were examined. Our study identified 4 lipid metabolites associated with abdominal obesity, including PC3 (O-21:2), SM (d21:1), PG (43:6), and one did not match with any candidate compounds in the databases. PC3 (O-21:2) and SM (d21:1) were significantly associated with blood glucose. Mediation analysis showed that all three lipid metabolites [PC3 (O-21:2), SM (d21:1), PG (43:6)] may mediate the association between abdominal obesity and abnormal glucose regulation. This study identified several novel obesity-related lipid metabolites.

Prevalence of and Factors Associated With Tobacco Dependence Among Adolescents Aged 12-16 Years Who Were Currently Smoking Tobacco in 125 Countries or Territories, 2012-2019.

Objectives. To examine the global prevalence of and factors associated with tobacco dependence among adolescents who are currently smoking. Methods. We obtained 2012 to 2019 Global Youth Tobacco Survey data on 67 406 adolescents aged 12 to 16 years from 125 countries or territories (hereafter countries). Those with tobacco dependence were defined as current smokers who felt a strong desire to smoke again within 24 hours after smoking or who had ever smoked or felt like smoking first thing in the morning. Results. The global prevalence of tobacco dependence among adolescents who were currently smoking was 38.4% (95% confidence interval [CI] = 34.0, 42.7). The prevalence was highest in high-income countries (49.8%; 95% CI = 47.0, 52.6) and lowest in lower-middle-income countries (31.2%; 95% CI = 26.9, 35.4). Secondhand smoke exposure, parental smoking, smoking among closest friends, tobacco advertisement exposure, and offers of free tobacco products were positively associated with tobacco dependence. Conclusions. Nearly 40% of adolescents who are currently smoking have tobacco dependence worldwide. Public Health Implications. Our findings emphasize the need to develop tobacco control interventions to prevent experimentation from progressing to regular smoking among adolescents who are currently smoking tobacco. (Am J Public Health. 2023;113(8):861-869. https://doi.org/10.2105/AJPH.2023.307283).

The number of metabolic syndrome risk factors predicts alterations in gut microbiota in Chinese children from the Huantai study.

BACKGROUND: Evidence on the effect of gut microbiota on the number of metabolic syndrome (MetS) risk factors among children is scarce. We aimed to examine the alterations of gut microbiota with different numbers of MetS risk factors among children. METHODS: Data were collected from a nested case-control study at the baseline of the Huantai Childhood Cardiovascular Health Cohort Study in Zibo, China. We compared the differences in gut microbiota based on 16S rRNA gene sequencing among 72 children with different numbers of MetS risk factors matched by age and sex (i.e., none, one, and two-or-more MetS risk factors; 24 children for each group). RESULTS: The community richness (i.e., the total number of species in the community) and diversity (i.e., the richness and evenness of species in the community) of gut microbiota decreased with an increased number of MetS risk factors in children (P for trend < 0.05). Among genera with a relative abundance greater than 0.01%, the relative abundance of Lachnoclostridium (PFDR = 0.009) increased in the MetS risk groups, whereas Alistipes (PFDR < 0.001) and Lachnospiraceae_NK4A136_group (PFDR = 0.043) decreased in the MetS risk groups compared to the non-risk group. The genus Christensenellaceae_R-7_group excelled at distinguishing one and two-or-more risk groups from the non-risk group (area under the ROC curve [AUC]: 0.84 - 0.92), while the genera Family_XIII_AD3011_group (AUC: 0.73 - 0.91) and Lachnoclostridium (AUC: 0.77 - 0.80) performed moderate abilities in identifying none, one, and two-or-more MetS risk factors in children. CONCLUSIONS: Based on the nested case-control study and the 16S rRNA gene sequencing technology, we found that dysbiosis of gut microbiota, particularly for the genera Christensenellaceae_R-7_group, Family_XIII_AD3011_group, and Lachnoclostridium may contribute to the early detection and the accumulation of MetS risk factors in childhood.

Estimating future PM2.5-attributed acute myocardial infarction incident cases under climate mitigation and population change scenarios in Shandong Province, China.

BACKGROUND: The effects of fine particulate matter (PM2.5) on acute myocardial infarction (AMI) have been widely recognized. However, no studies have comprehensively evaluated future PM2.5-attributed AMI burdens under different climate mitigation and population change scenarios. We aimed to quantify the PM2.5-AMI association and estimate the future change in PM2.5-attributed AMI incident cases under six integrated scenarios in 2030 and 2060 in Shandong Province, China. METHODS: Daily AMI incident cases and air pollutant data were collected from 136 districts/counties in Shandong Province from 2017 - 2019. A two-stage analysis with a distributed lag nonlinear model was conducted to quantify the baseline PM2.5-AMI association. The future change in PM2.5-attributed AMI incident cases was estimated by combining the fitted PM2.5-AMI association with the projected daily PM2.5 concentrations under six integrated scenarios. We further analyzed the factors driving changes in PM2.5-related AMI incidence using a decomposition method. RESULTS: Each 10 µg/m3 increase in PM2.5 exposure at lag05 was related to an excess risk of 1.3 % (95 % confidence intervals: 0.9 %, 1.7 %) for AMI incidence from 2017 - 2019 in Shandong Province. The estimated total PM2.5-attributed AMI incident cases would increase by 10.9-125.9 % and 6.4-244.6 % under Scenarios 1 - 3 in 2030 and 2060, whereas they would decrease by 0.9-5.2 % and 33.0-46.2 % under Scenarios 5 - 6 in 2030 and 2060, respectively. Furthermore, the percentage increases in PM2.5-attributed female cases (2030: -0.3 % to 135.1 %; 2060: -33.2 % to 321.5 %) and aging cases (2030: 15.2-171.8 %; 2060: -21.5 % to 394.2 %) would wholly exceed those in male cases (2030: -1.8 % to 133.2 %; 2060: -41.1 % to 264.3 %) and non-aging cases (2030: -41.0 % to 45.7 %; 2060: -89.5 % to -17.0 %) under six scenarios in 2030 and 2060. Population aging is the main driver of increased PM2.5-related AMI incidence under Scenarios 1 - 3 in 2030 and 2060, while improved air quality can offset these negative effects of population aging under the implementation of the carbon neutrality and 1.5 °C targets. CONCLUSION: The combination of ambitious climate policies (i.e., 1.5 °C warming limits and carbon neutrality targets) with stringent clean air policies is necessary to reduce the health impacts of air pollution in Shandong Province, China, regardless of population aging.

Chili pepper intake and all-cause and disease-specific mortality.

Background: Chili pepper has been used for the treatment and prevention of multiple diseases. This may be due to its abundance of bioactive components, such as carotenoids, which are well known for their antioxidant properties. To date, several prospective cohort studies have examined the association between chili pepper intake and mortality, but the results have not been consistent. This study aimed to clarify the association between chili pepper intake and all-cause and disease-specific mortality using a meta-analysis. Methods: PubMed, Embase, and ISI Web of Science databases were searched up to December 20, 2020, and reference lists of included studies were manually reviewed. All prospective cohort studies on the association between chili pepper intake and all-cause, cardiovascular disease (CVD)-specific, and cancer-specific mortality were included in this study. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in the meta-analysis. Between-study heterogeneity was assessed using I2 statistic and Q test. Results: A total of 4 cohort studies (N=564,748; all four studies had adjusted for important potential confounders such as demographic variables, dietary intake, and physical activity) were ultimately included in this meta-analysis. Among them, 31,527 died due to all causes, 10,184 died due to CVD, and 9,868 died due to cancer. Compared to none or rare consumption of chili pepper, consumption of chili pepper (ever or more than once a week) could significantly reduce the risk of all-cause mortality (summary adjusted HR: 0.87, 95% CI: 0.85, 0.90), CVD-specific mortality (summary adjusted HR: 0.89, 95% CI: 0.85, 0.93), and cancer-specific mortality (summary adjusted HR: 0.92, 95% CI: 0.88, 0.97). There was no significant between-study heterogeneity in the analyses (all-cause mortality: I2=0.7%, P=0.389; CVD-specific mortality: I2=21.8%, P=0.280; cancer-specific mortality: I2=0.0%, P=0.918). Conclusions: The present meta-analysis confirmed that chili pepper intake could reduce the risk of all-cause, CVD-specific, and cancer-specific mortality, suggesting that chili pepper may be a beneficial ingredient in the diets in prolonging life.

Association between gut microbiota and obesity combined with high carotid intima-media thickness among Chinese children.

BACKGROUND AND OBJECTIVES: Obesity and related target organ damage such as high carotid intima-media thickness (cIMT) in children is associated with cardiovascular disease (CVD) later in life. However, the asso-ciation between gut microbiota and obesity combined with high cIMT among children remains unclear. Therefore, we compared differences in composition, community diversity, and richness of gut microbiota among normal children and obesity combined with or without high cIMT to identify differential microbiota biomarkers. METHODS AND STUDY DESIGN: A total of 24 children with obesity combined with high cIMT (OB+high-cIMT), 24 with obesity but normal cIMT (OB+non-high cIMT), and 24 with normal weight and normal cIMT aged 10-11 years matched by age and sex from the "Huantai Childhood Cardiovascular Health Cohort Study" were included. All included fecal samples were tested using 16S rRNA gene sequencing. RESULTS: The community richness and diversity of gut microbiota in OB+high-cIMT children were decreased compared with OB+non-high cIMT children and normal children. At the genus level, the relative abundances of Christensenellaceae_R-7_group, UBA1819, Family_XIII_AD3011_group, and unclassi-fied_o_Bacteroidales were associated with reduced odds of OB+high-cIMT among children. Receiver operating characteristic (ROC) analysis showed that combined Christensenellaceae_R-7_group, UBA1819, Fami-ly_XIII_AD3011_group, and unclassified_o_Bacteroidales performed a high ability in identifying OB+high-cIMT. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed that several pathways such as biosynthesis of amino acids and aminoacyl-tRNA pathways were lower in the OB+high-cIMT group compared with the normal group. CONCLUSIONS: We found that the alteration of gut microbiota was associated with OB+high-cIMT among children, which indicates that the gut microbiota may be a marker for obesity and related cardiovascular damage among children.

Smoking control in China: A need for comprehensive national legislation.

In this Perspective, Bo Xi and Costan Magnussen discuss the trends in smoking prevalence in China reported by Mei Zhang and colleagues, and the need for effective tobacco control strategies.

Prevalence and trend of smokeless tobacco use and its associated factors among adolescents aged 12-16 years in 138 countries/territories, 1999-2019.

BACKGROUND: Smokeless tobacco use is popular in some regions worldwide, but it receives less attention compared to cigarette smoking. We aimed to estimate the recent prevalence of, and trends in, smokeless tobacco use and to examine its associated factors among adolescents aged 12-16 years in 138 countries/territories (hereafter "countries") from 1999 to 2019. METHODS: Data from the Global Youth Tobacco Survey conducted in 138 countries in 2010-2019 and the National Youth Tobacco Survey conducted in the United States in 2019 were used to calculate the prevalence of current smokeless tobacco use and investigate its associated factors among adolescents aged 12-16 years. We also assessed the trend in the prevalence of smokeless tobacco use in 100 countries that had conducted more than one survey from 1999 to 2019. RESULTS: The overall prevalence of current smokeless tobacco use was 4.4% (95% confidence interval [CI] 4.0-4.9), with 5.7% (5.1-6.3) for boys, 3.1% (2.6-3.5) for girls, 3.9% (3.5-4.4) for adolescents aged 12-14 years and 5.4% (4.8-5.9) for those aged 15-16 years. The prevalence was highest in the South-East Asian region (6.1%, 4.4-7.7) and lowest in the Western Pacific region (2.0%, 1.7-2.4). The prevalence of smokeless tobacco use decreased in 57 of 100 countries, increased in 32 countries, and remained unchanged in 11 countries. Current cigarette smoking (odds ratio [OR]=2.00, 95% CI=1.68-2.39), other tobacco product use (OR=6.03, 95% CI=4.92-7.40), tobacco advertisement exposure (OR=1.44, 95% CI=1.19-1.74), being offered free tobacco products (OR=2.01, 95% CI=1.66-2.42), and not being taught about dangers of smoking (OR=1.28, 95% CI=1.09-1.50) were all positively associated with current smokeless tobacco use. CONCLUSIONS: Smokeless tobacco use among adolescents remains a public health concern worldwide. Although the prevalence among adolescents decreased in most countries, it remains high especially in the South-East Asian region. More strict and effective strategies and measures are needed to further curb the smokeless tobacco use among adolescents.

Maternal cigarette smoking before or during pregnancy increases the risk of birth congenital anomalies: a population-based retrospective cohort study of 12 million mother-infant pairs.

BACKGROUND: The associations of maternal cigarette smoking with congenital anomalies in offspring have been inconsistent. This study aimed to clarify the associations of the timing and intensity of maternal cigarette smoking with 12 subtypes of birth congenital anomalies based on a nationwide large birth cohort in the USA. METHODS: We used nationwide birth certificate data from the US National Vital Statistics System during 2016-2019. Women reported the average daily number of cigarettes they consumed 3 months before pregnancy and in each subsequent trimester during pregnancy. Twelve subtypes of congenital anomalies were identified in medical records. Poisson regression analysis was used to estimate the risk ratios (RRs) with 95% confidence intervals (CIs) for 12 subtypes of congenital anomalies associated with the timing (i.e., before pregnancy, and during three different trimesters of pregnancy) and intensity (i.e., number of cigarettes consumed per day) of maternal cigarette smoking. RESULTS: Among the 12,144,972 women included, 9.3% smoked before pregnancy and 7.0%, 6.0%, and 5.7% in the first, second, and third trimester, respectively. Maternal smoking before or during pregnancy significantly increased the risk of six subtypes of birth congenital anomalies (i.e., congenital diaphragmatic hernia, gastroschisis, limb reduction defect, cleft lip with or without cleft palate, cleft palate alone, and hypospadias), even as low as 1-5 cigarettes per day. The adjusted RRs (95% CIs) for overall birth congenital anomalies (defined as having any one of the congenital malformations above significantly associated with maternal cigarette smoking) among women who smoked 1-5, 6-10, and ≥ 11 cigarettes per day before pregnancy were 1.31 (1.22-1.41), 1.25 (1.17-1.33), and 1.35 (1.28-1.43), respectively. Corresponding values were 1.23 (1.14-1.33), 1.33 (1.24-1.42), 1.33 (1.23-1.43), respectively, for women who smoked cigarettes in the first trimester; 1.32 (1.21-1.44), 1.36 (1.26-1.47), and 1.38 (1.23-1.54), respectively, for women who smoked cigarettes in the second trimester; and 1.33 (1.22-1.44), 1.35 (1.24-1.47), and 1.35 (1.19-1.52), respectively, for women who smoked cigarettes in the third trimester. Compared with women who kept smoking before and throughout pregnancy, women who never smoked had significantly lower risk of congenital anomalies (RR 0.77, 95% CI 0.73-0.81), but women who smoked before pregnancy and quitted during each trimester of pregnancy had no reduced risk (all P > 0.05). CONCLUSIONS: Maternal smoking before or during pregnancy increased the risk of several birth congenital anomalies, even as low as 1-5 cigarettes per day. Maternal smokers who stopped smoking in the subsequent trimesters of pregnancy were still at an increased risk of birth congenital anomalies. Our findings highlighted that smoking cessation interventions should be implemented before pregnancy.

Childhood diabetes mellitus and early-onset kidney diseases later in life: a nationwide population-based matched cohort study.

BACKGROUND: The empirical evidence remains inconclusive for an association between diabetes mellitus (DM) in children and early-onset kidney disease later in life, and little is known about the effects of DM types (i.e., type 1 diabetes [T1DM] and type 2 diabetes [T2DM]) in childhood on type-specific kidney diseases. We aimed to evaluate the association of childhood DM with overall and type-specific early-onset kidney diseases later in life. METHODS: The population-based matched cohort study included 9356 individuals with DM (T1DM: 8470, T2DM: 886) diagnosed in childhood (< 18 years) who were born between 1977 and 2016, and 93,560 individuals without DM matched on sex and year of birth in Denmark. The main outcomes were overall and type-specific early-onset kidney diseases. The follow-up period of all included participants was from the date of DM diagnosis in the exposure group until the first diagnosis of kidney disease, emigration, or 31 December 2018, whichever came first. RESULTS: During a median follow-up of 13 years, children with DM had a 154% increased risk of early-onset kidney diseases than children without DM (adjusted hazard ratios 2.54, 95% confidence intervals 2.38-2.72), and T1DM (2.48, 2.31-2.67) and T2DM (2.75, 2.28-3.31) showed similar results. Children with DM also had a higher risk of multiple specific kidney diseases including glomerular diseases, renal tubulo-interstitial diseases, renal failure, and urolithiasis. The risks of type-specific kidney diseases including glomerular diseases and renal failure tended to be higher for children with T2DM (glomerular diseases: 5.84, 3.69-9.24; renal failure: 14.77, 8.53-25.59) than those with T1DM (glomerular diseases: 3.14, 2.57-3.83; renal failure: 8.24, 6.66-10.20). CONCLUSIONS: Children with DM had a higher increased risk of early-onset overall and specific kidney diseases later in life. Early prevention and treatment of both T1DM and T2DM in childhood may significantly reduce the risk of kidney diseases later in life.