[Epidemiological characteristics of cardio-metabolic risk factors in women aged 15-49 years in 4 provinces of China in 2018].

OBJECTIVE: To analyze the prevalence of cardio-metabolic(CM) risk in women aged 15-49 years in 4 provinces of China and the influence of socioeconomic factors on them. METHODS: A total of 2851 women aged 15-49 years from Community-based Cohort Study on Nervous System Disease in 2018 were selected. Obesity, central obesity, elevated triglyceride(TG), elevated total cholesterol(TC), decreased high-density lipoprotein cholesterol(HDL-C), elevated low-density lipoprotein cholesterol(LDL-C), elevated blood pressure, elevated blood glucose and risk factor aggregation were analyzed. χ~2 test was used for univariate analysis, multinomial Logit model was used to evaluate the relationship between socioeconomic factors and CM risk factors, and Cochran-Armitage trend test was used for trend analysis. RESULTS: The detection rate of CM risk factors in this study from high to low were central obesity(26.76%), overweight(22.41%), pre central obesity(17.47%), decreased HDL-C(15.36%), elevated TG(11.78%), borderline elevated TC(11.40%), borderline elevated TG(11.12%), elevated blood pressure(9.71%) and hypertension(9.12%). The prevalence rates of CM risk factors were different among different age groups, income groups and education levels(P<0.05). In addition to decreased HDL-C, the prevalence of other metabolic risk factors increased with age(P_(trend)<0.05). With the improvement of educational level, the prevalence rates of overweight, obesity, central obesity, central obesity, elevated TG, decreased HDL-C, elevated blood pressure, hypertension, elevated blood pressure and diabetes showed a downward trend(P_(trend)<0.05). Multinomial Logit model showed that the rick of metabolic risk factors in the age group of 40 to 49 years old was higher than that in the younger age group aged 15-29 years, and was more significant in hypertension, elevated blood pressure and elevated blood glucose, which were 8.51 times(95% CI 5.45-13.27), 3.14 times(95%CI 2.20-4.48)and 2.66(95% CI 1.52-4.66)times of the younger age group, respectively. Women with high-income level have a higher risk of borderline elevated TC, elevated TC and borderline elevated LDL-C(OR=1.85, 95% CI 1.44-2.38;OR=2.01, 95% CI 1.25-3.22;OR=2.16, 95% CI 1.61-2.90), but the lower risk of overweight and elevated blood pressure(OR=0.79, 95% CI 0.64-0.98;OR=0.69, 95% CI 0.50-0.94). The risk of obesity, hypertension and diabetes of people with college degree or above was about 50% lower than those with junior high school education or below(OR=0.52, 95% CI 0.35-0.78;OR=0.43, 95% CI 0.27-0.67; OR=0.52, 95% CI 0.28-0.96). CONCLUSION: Central obesity, overweight, pre central obesity and HDL-C decrease were prominent CM risk factors in women aged 15-49 years in four provinces of China in 2018. The detection rate of CM risk factors is higher in women of high age group or low education level.

Activin Receptor-Like Kinase 3 Directly Couples Gαq (Guanine Nucleotide-Binding Protein Subunit αq)/ Gαq (Guanine Nucleotide-Binding Protein Subunit α11) to Regulate Vascular Contractility.

BACKGROUND: Vascular smooth muscle cell (VSMC) contractility is critical for blood pressure regulation and vascular homeostasis. Identifying the key molecule that maintains VSMC contractility may provide a novel therapeutic target for vascular remodeling. ALK3 (activin receptor-like kinase 3) is a serine/threonine kinase receptor, and deletion of ALK3 causes embryonic lethality. However, little is known about the role of ALK3 in postnatal arterial function and homeostasis. METHODS: We conducted in vivo studies in a tamoxifen-induced postnatal VSMC-specific ALK3 deletion mice suitable for analysis of blood pressure and vascular contractility. Additionally, the role of ALK3 on VSMC was determined using Western blot, collagen-based contraction assay and traction force microscopy. Furthermore, interactome analysis were performed to identify the ALK3-associated proteins and bioluminescence resonance energy transfer assay was used to characterize Gαq activation. RESULTS: ALK3 deficiency in VSMC led to spontaneous hypotension and impaired response to angiotensin II in mice. In vivo and in vitro data revealed that ALK3 deficiency impaired contraction force generation by VSMCs, repressed the expression of contractile proteins, and inhibited the phosphorylation of myosin light chain. Mechanistically, Smad1/5/8 signaling mediated the ALK3-modulated contractile protein expressions but not myosin light chain phosphorylation. Furthermore, interactome analysis revealed that ALK3 directly interacted with and activated Gαq (guanine nucleotide-binding protein subunit αq)/Gα11 (guanine nucleotide-binding protein subunit α11), thereby stimulating myosin light chain phosphorylation and VSMC contraction. CONCLUSIONS: Our study revealed that in addition to canonical Smad1/5/8 signaling, ALK3 modulates VSMC contractility through direct interaction with Gαq/Gα11, and therefore, might serve as a potential target for modulating aortic wall homeostasis.

[Analysis of differentiated regional dietary structures of adults aged 18-64 years in 15 provinces (autonomous regions, municipalities) of China in 2018].

OBJECTIVE: To analyze the status of energy and macronutrient intake among adults aged 18 to 64 years old in 15 provinces(autonomous regions and municipalities) of China. METHODS: A sample of 9481 adults aged 18-64 years from the data of the China Health and Nutrition Survey in 2018 was analyzed. Three consecutive days of 24 h recalls combined with the weighing of household seasonings were used to collect information on food intake and condiment intake. Food consumption was converted into energy and various nutrient intakes by the China Food Composition Table. RESULTS: The median daily intakes of energy were 1942.28 kcal and 1951.14 kcal in urban and rural areas, 1796.94 kcal, 1972.89 kcal, 1989.61 kcal and 1908.98 kcal in northwest, southwest, southeast and northern regions, respectively. The energy supply ratio of protein and fat were 13.61% and 35.85%, respectively, higher than 12.31% and 34.45% in rural areas, while the energy supply ratio of carbohydrates in urban(49.62%) was lower than that in rural areas(52.18%). The energy supply ratios of fat in the southwest and southeast regions were 38.90% and 36.80%, respectively, while the energy supply ratios of carbohydrates were 47.70% and 47.93%. The main food sources of energy, protein, and fat are different in different regions. The percentage of energy, protein, and fat from animal foods decreased with increasing age groups. The adults with low-income levels had a high intake of carbohydrates but a low intake of protein, and the adults with high-income levels had high proportions of energy, protein and fat from animal food sources. CONCLUSION: The total energy intakes of residents in different regions are relatively ideal, but the dietary structures are still unreasonable, and the energy supply ratios of fat are relatively high, especially in the southwest and southeast regions. The intake and food sources of the three macronutrients are varied in different regions and urban and rural areas. Age and income level affect the food choices of residents.

Longitudinal relationship between body fat percentage and risk of type 2 diabetes in Chinese adults: Evidence from the China Health and Nutrition Survey.

Objective: Body fat percentage (BF%) might be an alternative index of obesity which is the major risk factor for developing type 2 diabetes (T2D). We aim to longitudinally evaluated the relationship between BF% and risk of T2D. Methods: A sample of 5,595 adults aged 18-65 who participated in two waves of China Health and Nutrition Survey (CHNS 2015 and 2018) was analyzed. Two level mixed-effects modified Poisson regression with robust estimation of variance stratified by sex was used to evaluate the risk ratios (RRs) for T2D according to quintiles of BF%, and the curves of receiver operating characteristic (ROC) were plotted to identify the optimal total and trunk BF% cut-off points for predicting an increased T2D risk. Results: In males, compared with subjects in the first quintile of total BF%, those in the third (RR = 2.03, 95% CI 1.09-3.79), fourth (RR = 2.56, 95%CI 1.46-4.48), and fifth (RR = 2.16, 95%CI 1.22-3.82) quintile had higher risk of T2D after adjusting for all potential confounders (p-trend < 0.001). For females, the RR (95% CI) was 1.92 (1.14, 3.24) in the fifth quintile (p-trend = 0.014). Males and females with a trunk BF% >25.5 and 34.4% (≥ quintile 4), respectively, were at significantly increased risk of T2D (p-trend = 0.001). Besides, the optimal cut-off values of total and trunk BF% were 21.9 and 25.2% for males, and 36.7 and 30.3% for females, respectively. Conclusions: The incident risk of T2D significantly increased over specific level of total and trunk BF% in both Chinese males and females, and the optimal BF% cut-off values were valuable for clinical application of BF% based on sex difference, which may be a cost-effective implementation for prevention and treatment of T2D in China.

A Calcium Phosphate-Induced Mouse Abdominal Aortic Aneurysm Model.

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease that occurs worldwide and is characterized by irreversible dilation of the abdominal aorta. Currently, several chemically induced murine AAA models are used, each simulating a different aspect of the pathogenesis of AAA. The calcium phosphate-induced AAA model is a rapid and cost-effective model compared to the angiotensin II- and elastase-induced AAA models. The application of CaPO4 crystals to the mouse aorta results in elastic fiber degradation, loss of smooth muscle cells, inflammation, and calcium deposition associated with aortic dilation. This article introduces a standard protocol for the CaPO4-induced AAA model. The protocol includes material preparation, the surgical application of the CaPO4 to the adventitia of the infrarenal abdominal aorta, the harvesting of aortas to visualize aortic aneurysms, and histological analyses in mice.

PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing.

BACKGROUND: Phenotypic transition of vascular smooth muscle cells (VSMCs) accounts for the pathogenesis of a variety of vascular diseases during the early stage. Recent studies indicate the metabolic reprogramming may be involved in VSMC phenotypic transition. However, the definite molecules that link energy metabolism to distinct VSMC phenotype remain elusive. METHODS: A carotid artery injury model was used to study postinjury neointima formation as well as VSMC phenotypic transition in vivo. RNA-seq analysis, cell migration assay, collagen gel contraction assay, wire myography assay, immunoblotting, protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: We collected cell energy-regulating genes by using Gene Ontology annotation and applied RNA-Seq analysis of transforming growth factor-ß or platelet-derived growth factor BB stimulated VSMCs. Six candidate genes were overlapped from energy metabolism-related genes and genes reciprocally upregulated by transforming growth factor-ß and downregulated by platelet-derived growth factor BB. Among them, prohibitin 2 has been reported to regulate mitochondrial oxidative phosphorylation. Indeed, prohibitin 2-deficient VSMCs lost the contractile phenotype as evidenced by reduced contractile proteins. Consistently, Phb2SMCKO mice were more susceptible to postinjury VSMC proliferation and neointima formation compared with Phb2flox/flox mice. Further protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay revealed that prohibitin 2, through its C-terminus, directly interacts with hnRNPA1, a key modulator of pyruvate kinase M1/2 (PKM) mRNA splicing that promotes PKM2 expression and glycolysis. Prohibitin 2 deficiency facilitated PKM1/2 mRNA splicing and reversion from PKM1 to PKM2, and enhanced glycolysis in VSMCs. Blocking prohibitin 2-hnRNPA1 interaction resulted in increased PKM2 expression, enhanced glycolysis, repressed contractile marker genes expression in VSMCs, as well as aggravated postinjury neointima formation in vivo. CONCLUSIONS: Prohibitin 2 maintains VSMC contractile phenotype by interacting with hnRNPA1 to counteract hnRNPA1-mediated PKM alternative splicing and glucose metabolic reprogramming.

Association of obesity profiles with type 2 diabetes in Chinese adults: Findings from the China health and nutrition survey.

Aims: To examine longitudinal associations of obesity profiles, continuous BMI, and waist circumference (WC) with the risk of type 2 diabetes in Chinese adults. Methods: Data were derived from three waves (2009, 2015, and 2018) of the China Health and Nutrition Survey, and 3,595 adults aged 18-65 years who participated in at least two waves of the survey and had completed data were analyzed. Obesity profiles included BMI- or WC-related single obesity and combined obesity. Combined obesity was categorized into six groups including Group 1 with normal BMI and WC, Group 2 with normal BMI but pre-abdominal obesity, Group 3 with normal BMI but abdominal obesity, Group 4 with abnormal BMI (overweight and general obesity) and normal WC, Group 5 with abnormal BMI and pre-abdominal obesity, and Group 6 with abnormal BMI and abdominal obesity. Three-level mixed-effects logistic regressions with random intercept stratified by gender and restricted cubic splines were performed to examine ORs and 95%CIs for the risk of type 2 diabetes. Results: In men, compared with subjects of Group 1, those in Group 3 had higher risk, with an OR of 4.83 (95% CI: 1.99-11.74), followed by those in Group 6 (OR = 4.05, 95%CI: 2.32-7.08) and Group 5 (OR = 2.98, 95%CI: 1.51-5.87) after adjusting for all potential confounders. For women, the subject of Group 6 had highest risk (OR = 8.79, 95%CI: 4.04-19.12), followed by Group 3 (OR = 3.30, 95%CI: 1.23-8.86) and Group 5 (OR = 3.16, 95%CI: 1.21-8.26). No significant association between abnormal BMI and normal WC (Group 4) was observed in both genders. Type 2 diabetes risk increased steeply at BMI of 23.5 kg/m2 and 22.5 kg/m2 or higher, and WC of 82.0 cm and 83.0 cm or higher in Chinese adult men and women, respectively (p for overall <0.001). Conclusion: Chinese adults with pre-abdominal or abdominal obesity had a relative high risk of type 2 diabetes independent of BMI levels. Lower BMI (≤23.5 kg/m2 for men and ≤22.5 kg/m2 for women) and lower WC (82.0 cm for men and ≤83.0 cm for women) values than the current Chinese obesity cut-offs were found to predict the risk of type 2 diabetes. These findings urge to inform WC modification and optimization of early screening guidelines.

A Comparison between Dietary Consumption Status and Healthy Dietary Pattern among Adults Aged 55 and Older in China.

The nutrition and health of middle-aged and elderly people is crucial to the long-term development of a country. The present study aimed to analyze the dietary consumption status in Chinese adults by using baseline and follow-up data from the community-based Cohort Study on Nervous System Diseases between 2018−2020 and selecting those aged 55 and older (n = 23,296). Dividing 65 food items into 17 subgroups on the basis of a valid semi-quantitative food frequency questionnaire, we analyze the consumption amount and consumption rate of foods in relation to wave and sociodemographic factors by employing the Wilcoxon rank sum test, Kruskal−Wallis analysis, the Chi-squared test, and the Cochran−Armitage trend test and evaluate food intake status using the Chinese Dietary Guidelines Recommendations (2022). Compared to 2018, the median daily intake of livestock meat, poultry, and eggs increased in 2020 (p < 0.05), while the median daily intake of wheat, other cereals, tubers, legumes, fruits, and fish and seafood decreased (p < 0.05). The proportion of subjects with excessive intake of grain, livestock and poultry, and eggs was 46.3%, 36.6%, and 26.6%, respectively, while the proportion of subjects with insufficient intake of whole grains and mixed beans, tubers, legumes, dairy products, fruits, vegetables, and fish and seafood were 98.4%, 80.3%, 74.0%, 94.6%, 94.3%, 75.8%, and 86.5%, respectively, and more than 50% of subjects were non-consumers of dairy products, nuts, and whole grains and mixed beans. In conclusion, the problem of unhealthy dietary structure is prominent among adults aged 55 and older in China; insufficient or excessive intakes of various types of foods are common; and excessive consumption of edible oil and salt remains a serious problem.

Restoring apoptosis dysregulation using survivin inhibitor in nasopharyngeal cancer.

BACKGROUND: Restoring apoptosis dysregulation via survivin inhibition has been investigated in several cancers. In Epstein-Barr Virus (EBV)-driven nasopharyngeal cancer (NPC), virally induced oncogenes can upregulate survivin. Therefore, we seek to investigate the therapeutic efficacy of YM-155 (a survivin inhibitor) in NPC, both in vitro and in vivo models. METHODS: Cytotoxicity, apoptosis, and active-caspase 3 expression assays were performed. RESULTS: Both NPC tissue and cells expressed high levels of survivin which were inhibited by YM-155 in a dose-dependent manner. In addition, YM-155 induced apoptosis of NPC cells with an IC50 of 100 nM and inhibited tumor growth in vivo (P < 0.05). YM-155 in combination with cisplatin or radiation significantly increased overall cytotoxicity as compared to YM-155 monotherapy. In the xenograft model, YM-155 plus radiation additively achieved significantly higher percentage of active-caspase 3-positive tumor cells than radiation alone (P < 0.05). CONCLUSIONS: YM-155 is a potential therapeutic agent for NPC through inhibiting survivin and restoring apoptosis dysregulation.

TIP60-miR-22 axis as a prognostic marker of breast cancer progression.

MicroRNAs (miRNAs) are 22- to 24-nucleotide, small, non-coding RNAs that bind to the 3'UTR of target genes to control gene expression. Consequently, their dysregulation contributes to many diseases, including diabetes and cancer. miR-22 is up-regulated in numerous metastatic cancers and recent studies have suggested a role for miR-22 in promoting stemness and metastasis. TIP60 is a lysine acetyl-transferase reported to be down-regulated in cancer but the molecular mechanism of this reduction is still unclear. In this study, we identify TIP60 as a target of miR-22. We show a negative correlation in the expression of TIP60 and miR-22 in breast cancer patients, and show that low levels of TIP60 and high levels of miR-22 are associated with poor overall survival. Furthermore, pathway analysis using high miR-22/low TIP60 and low miR-22/high TIP60 breast cancer patient datasets suggests association of TIP60/miR-22 with epithelial-mesenchymal transition (EMT), a key alteration in progression of cancer cells. We show that blocking endogenous miR-22 can restore TIP60 levels, which in turn decreases the migration and invasion capacity of metastatic breast cancer cell line. These results provide mechanistic insight into TIP60 regulation and evidence for the utility of the combination of TIP60 and miR-22 as prognostic indicator of breast cancer progression.