Trends in urban/rural inequalities in physical growth among Chinese children over three decades of urbanization in Guangzhou: 1985-2015.

BACKGROUND: Great growth inequalities between urban and rural areas have been reported in China over the past years. By examining urban/rural inequalities in physical growth among children < 7 years old over the past three decades from 1985 to 2015 in Guangzhou, we analyzed altering trends of anthropometric data in children and their association with economic development during the period of rapid urbanization in Guangzhou. METHODS: The height, body weight and nutrition status of children under 7 years old were obtained from two successive cross-sectional surveys and one health surveillance system. Student's t-test, Spearman's rank-order correlation and polynomial regression were used to assess the difference in physical growth between children in urban and rural areas and the association between socioeconomic index and secular growth changes. RESULTS: A height and weight difference was found between urban and rural children aged 0-6 years during the first two decades of our research (1985-2005), which gradually narrowed in both sex groups over time. By the end of 2015, elder boys (age group ≥5 year) and girls (age group ≥4 year) in rural areas were taller than their counterparts in urban areas (p < 0.05).The same trend could be witnessed in the weight of children aged 6 years, with a - 1.30 kg difference (P = 0.03) for boys, and a - 0.05 difference (P = 0.82) for girls. When GDP increased, the gap in boys' weight-for-age z-score (WAZ from 0.25 to 0.01) and height-for-age z-score (HAZ from 0.55 to 0.03) between urban and rural areas diminished, and disappeared when the GDP per capita (USD) approached 25,000. In either urban or rural areas, the urbanization rate and GDP were positively associated with the prevalence of obesity (all R > 0.90 with P < 0.05) and negatively correlated with the prevalence of stunted growth (all R < -0.87 with P < 0.05). CONCLUSION: Growth inequalities gradually decreased with economic development and urbanization, while new challenges such as obesity emerged. To eliminate health problems due to catch-up growth among rural children, comprehensive intervention programs for early child growth should be promoted in rural areas.

Impact of quercetin on systemic levels of inflammation: a meta-analysis of randomised controlled human trials.

Knowledge regarding the anti-inflammatory capability of quercetin remains inconclusive and controversial due to the heterogeneous methods and inconsistent results of RCTs. We performed a series of meta-analyses of RCTs to evaluate the impact of quercetin supplementation on inflammatory biomarkers. Three cytokines (CRP, IL-6, TNF-α) with enough eligible studies (n = 6, 5 and 4, respectively) were selected for further meta-analyses. Data from these RCTs were pooled, and both overall effect and stratified subgroup analyses were performed. No relevant overall effects on peripheral CRP, IL-6 and TNF-α were observed. Subgroup analyses revealed a significant reduction in circulating CRP in participants with diagnosed diseases (SMD: -0.24, 95% CI: -0.49, 0.00) and IL-6 in females (SMD: -1.37, 95% CI: -1.93, -0.81), subjects with diagnosed diseases (SMD: -1.37, 95% CI: -1.93, -0.81) and with high-dose interventions (SMD: -0.69, 95% CI: -1.10, -0.38). In conclusion, consumption of quercetin is a promising therapeutic strategy for chronic disease management.

Synergistic Association of Hepatitis B Surface Antigen and Plasma Epstein-Barr Virus DNA Load on Distant Metastasis in Patients With Nasopharyngeal Carcinoma.

Importance: Hepatitis B surface antigen (HBsAg) reportedly increases the risk of distant metastasis among patients with nasopharyngeal carcinoma (NPC). However, the associated potential interaction and changes in hazard ratios (HRs) between HBsAg and different plasma Epstein-Barr (EBV) DNA levels are unknown. Moreover, the potential HBsAg-positive-associated NPC metastatic mechanism remains unclear. Objective: To investigate the prognostic value and biological associations of HBsAg and plasma EBV DNA levels on distant metastasis in patients with NPC. Design, Setting, and Participants: Retrospective cohort study performed at Sun Yat-sen University Cancer Center between January 2010 and January 2013. A total of 792 patients with nonmetastatic NPC were enrolled. The median (range) follow-up time was 62.1 (1.4-83.4) months. Of these patients, 17.8% presented with HBsAg positivity. Cytological experiments were performed to evaluate the role of HBsAg in the invasion and migration of EBV-positive NPC cells. Data analysis was performed from July 2020 to April 2021. Main Outcomes and Measures: The primary end point was distant metastasis-free survival. Association rules were used to identify new rules related to distant metastasis. Interaction plots, univariate and multivariate Cox regression analyses, stratification analysis, and quantification using HRs were conducted. Additionally, cell migration and invasion assays, as well as Western blotting, were performed in the cytological validation. Results: Among the 792 patients, 576 (72.7%) were male, with a median (IQR) age of 45 (38-53) years. The HBsAg-positive group exhibited a significant interaction and increased risk of distant metastasis when plasma EBV DNA cutoff levels were 1.5 × 1000 copies/mL or greater. The HR was 9.16 (95% CI, 2.46-34.14) when the plasma EBV DNA load reached 6 × 1000 copies/mL, which was higher than that in patients with stage IV disease (HR, 2.01; 95% CI, 1.13-3.56; P = .02). In cytological experiments, HBsAg promoted epithelial-mesenchymal transition by upregulating vimentin and fibronectin in EBV-positive NPC cells in vitro, thereby promoting invasion and migration of EBV-positive NPC cells. Conclusions and Relevance: In this cohort study, the observed synergistic association between HBsAg and plasma EBV DNA load represented a novel potential mechanism underlying the increased risk of distant metastasis in patients with NPC. Hence, attention should be paid to patients with NPC with HBsAg positivity, especially when the plasma EBV DNA level is 6 × 1000 copies/mL or greater. Consideration of this synergistic association will contribute to more accurate individualized management.

Systematic construction and external validation of an immune-related prognostic model for nasopharyngeal carcinoma.

BACKGROUND: We attempted to identify the most reliable immune-related index for predicting nasopharyngeal carcinoma (NPC) prognosis and to reveal its precise and integrated relationship with NPC progression. METHOD: One thousand seven hundred and six patients with newly diagnosed NPC (1320 from the primary cohort and 386 from the validated cohort) from January 2010 to March 2014 were enrolled. Clinical features and 12 immune-related variables were analyzed. RESULTS: A high absolute lymphocyte count (ALC; >3.2 × 109 /L) correlated with a poor prognosis of patients with NPC. Significant OS differences were discovered between patients with high ALC and no ALC elevation (p < 0.05, in primary cohort), showing similar prognostic risk to patients with advanced NPC (p > 0.05, in validated cohort). ALC improved the predictive performance of the basic tumor-node-metastasis prognostic model (p = 0.025), which was reliably validated in the external independent cohort. CONCLUSION: High ALC is a surrogate marker for improved prognostic risk stratification in NPC.

Exercise retards ongoing adipose tissue fibrosis in diet-induced obese mice.

Exercise has been recommended as an important strategy to improve glucose metabolism in obesity. Adipose tissue fibrosis is associated with inflammation and is implicated in glucose metabolism disturbance and insulin resistance in obesity. However, the effect of exercise on the progression of adipose tissue fibrosis is still unknown. The aim of the present study was to investigate whether exercise retarded the progression of adipose tissue fibrosis and ameliorated glucose homeostasis in diet-induced obese mice. To do so, obesity and adipose tissue fibrosis in mice were induced by high-fat diet feeding for 12 weeks and the mice subsequently received high-fat diet and exercise intervention for another 12 weeks. Exercise alleviated high-fat diet-induced glucose intolerance and insulin resistance. Continued high-fat diet feeding exacerbated collagen deposition and further increased fibrosis-related gene expression in adipose tissue. Exercise attenuated or reversed these changes. Additionally, PPARγ, which has been shown to inhibit adipose tissue fibrosis, was observed to be increased following exercise. Moreover, exercise decreased the expression of HIF-1α in adipose fibrosis, and adipose tissue inflammation was inhibited. In conclusion, our data indicate that exercise attenuates and even reverses the progression of adipose tissue fibrosis, providing a plausible mechanism for its beneficial effects on glucose metabolism in obesity.

Grading and prognosis of weight loss before and after treatment with optimal cutoff values in nasopharyngeal carcinoma.

OBJECTIVES: Weight loss has been validated as a prognostic predictor of nasopharyngeal carcinoma (NPC); however, no global unitary indicator and criteria exist for the definition of weight loss as a prognostic factor. The aim of this study was to determine the most effective indicator for weight loss, evaluate its effect on the prognosis of NPC, and further propose a cutoff value to identify patients in need of nutritional care. METHODS: This retrospective cohort analysis with a median follow-up of 62.3 mo included 681 newly diagnosed patients with NPC. Principal component analysis was performed to select the best continuous variable including weight loss (kg; value of weight loss [VWL]), percent weight loss (PWL), and body mass index loss (BMIL). Multivariable Cox regression analysis and multiple correspondence analysis were performed to select the best cutoff values by different cutoff methods including the median, receiver operating characteristic curve, and threshold searching. RESULTS: PWL was the highest contributor to the prognosis of NPC compared with VWL and BMIL. Cutoff values of PWL (6.3 and 12.3%) were confirmed to be more important and were proposed to differentiate patients into low-, medium-, and high-risk NPC groups, with their 5-y progression-free survival (84.5 versus 77.9%, P = 0.046; 77.9 versus 67.3%, P = 0.046). PWL was an independent adverse prognostic factor (P = 0.002) for NPC. CONCLUSIONS: PWL is a promising predictor for NPC, and cutoff values could be validated for nutritional risk grading in patients with NPC. These stratified criteria may help accelerate the extensive application of grading nutritional management in NPC therapy.

Apoptotic cell induction of miR-10b in macrophages contributes to advanced atherosclerosis progression in ApoE-/- mice.

Aims: We previously found that miR-10b inhibits cholesterol efflux from thioglycollate-elicited mouse peritoneal macrophages through repressing ATP binding cassette transporter (ABCA1). Herein, we deciphered the mechanism underlying macrophage miR-10b expression and the role of miR-10b in atherosclerosis. Methods and results: MiR-10b expression was increased in the arteries with advanced but not early atherosclerotic plaques of ApoE-/- mice. Free cholesterol-induced macrophage apoptotic cells (FC-AM) promoted miR-10b expression in mouse resident peritoneal macrophages (RPM) by up-regulation of Twist1/2 in a Mer receptor tyrosine kinase dependent manner. Surprisingly, antagomiR-10b de-repressed ABCA1 in RPM engulfing FC-AM but not in RPM alone or RPM-derived foam cells; systemic delivery of antagomiR-10b enhanced reverse cholesterol transport from RPM engulfing FC-AM but not from RPM or the foam cells in ApoE-/- mice. Mechanistically, RPM engulfing FC-AM possessed sufficient miR-10b functionally repressing ABCA1 expression, whereas RPM and foam cells had little miR-10b incompetently repressing ABCA1 expression. Notably, antagomiR-10b administration reduced advanced plaque size and also enhanced plaque stability in ApoE-/-mice, which were associated with increased plaque macrophage ABCA1 expression and reduced plaque apoptosis and inflammation. However, antagomiR-10b administration did not affect early atherosclerotic plaque formation in ApoE-/- mice. Conclusion: These data suggest that apoptotic cell induction of miR-10b in macrophages is important in advanced atherosclerosis progression.

Quercetin protects against atherosclerosis by inhibiting dendritic cell activation.

SCOPE: Quercetin is a typical flavonol with atheroprotective effects, but the effect of quercetin on dendritic cell (DC) maturation in relation to atherosclerosis has not yet been clearly defined. Thus, we investigated whether quercetin can inhibit DC maturation and evaluated its potential value in atherosclerosis progression in ApoE-/- mice. METHODS AND RESULTS: Quercetin consumption inhibited DC activation, inflammatory response and suppressed the progression of atherosclerosis in ApoE-/- mice. Subsequently, quercetin treatment inhibited the phenotypic and functional maturation of DCs, as evidenced not only by downregulation of CD80, CD86, MHC-II, IL-6 and IL-12 but also by a reduction in the ability to stimulate T cell allogeneic proliferation. Finally, an in vitro study demonstrated that quercetin inhibited DC maturation via upregulation of Dabs, which then downregulated the Src/PI3K/Akt-NF-κB-inflammatory pathways. CONCLUSIONS: Our data indicate that quercetin attenuates atherosclerosis progression by regulating DC activation via Dab2 protein expression.

Established atherosclerosis might be a prerequisite for chicory and its constituent protocatechuic acid to promote endothelium-dependent vasodilation in mice.

SCOPE: Chicory (Cichorium intybus L. var. foliosum, Belgian endive), a typical Mediterranean vegetable, and its constituent protocatechuic acid (PCA) can inhibit established atherosclerosis progression. We thus investigated whether chicory can improve vascular relaxation, a critical pathway for combating atherosclerosis, and whether PCA is a contributor to a chicory-induced effect. METHODS AND RESULTS: Apolipoprotein E-deficient (ApoE-/- ) mice with established atherosclerosis and C57BL/6J mice without atherosclerosis were fed an AIN-93G diet, or AIN-93G plus 0.5% freeze-dried chicory or 0.003% PCA for 1 wk. In ApoE-/- mice, both chicory and PCA consumption increased endothelium-dependent vasodilation and endothelial nitric oxide synthase (eNOS) activity independent of eNOS and phospho-eNOS Ser1177 and Thr495 protein expression. Chicory- or PCA-induced eNOS activities were associated with increased vascular tetrahydrobiopterin (BH4 ) levels that result from reduced BH4 oxidation partially through preventing eNOS uncoupling. In C57BL/6J mice, neither chicory nor PCA consumption affected endothelium-dependent vasodilation and eNOS activity. Notably, in vitro studies showed that PCA increases eNOS activity in mouse aortic endothelial cells in co-culture with macrophage foam cells, but not in aortic endothelial cells alone. CONCLUSIONS: Chicory improves eNOS-mediated endothelium-dependent vasodilation by increasing BH4 levels in mice with established atherosclerosis, which might be partially ascribed to its constituent PCA.

Influence of Intestinal Microbiota on the Catabolism of Flavonoids in Mice.

Although in vitro studies have shown that flavonoids are metabolized into phenolic acids by the gut microbiota, the biotransformation of flavonoids by intestinal microbiota is seldom studied in vivo. In this study, we investigated the impact of the gut microbiota on the biotransformation of 3 subclasses of flavonoids (flavonols, flavones, and flavanones). The ability of intestinal microbiota to convert flavonoids was confirmed with an in vitro fermentation model using mouse gut microflora. Simultaneously, purified flavonoids were administered to control and antibiotic-treated mice by gavage, and the metabolism of these flavonoids was evaluated. p-Hydroxyphenylacetic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, hydrocaffeic acid, coumaric acid, and 3-(4-hydroxyphenyl)propionic acid were detected in the serum samples from the control mice after flavonoid consumption. The serum flavonoid concentrations were similar in both groups, whereas the phenolic metabolite concentrations were lower in the antibiotic-treated mice than in the control mice. We detected markedly higher flavonoids excretion in the feces and urine of the antibiotic-treated mice compared to the controls. Moreover, phenolic metabolites were upregulated in the control mice. These results suggest that the intestinal microbiota are not necessary for the absorption of flavonoids, but are required for their transformation.

Chicory, a typical vegetable in Mediterranean diet, exerts a therapeutic role in established atherosclerosis in apolipoprotein E-deficient mice.

SCOPE: Since protocatechuic acid exerts an atheroprotective role, we investigated how chicory (Cichorium intybus L. var. foliosum, Belgian endive) rich in protocatechuic acid, a typical vegetable in Mediterranean diet, affects preestablished atherosclerosis progression. METHODS AND RESULTS: Apolipoprotein E-deficient mice fed AIN diets containing 0.5% freeze-dried chicory for 10 weeks displayed a reduction in lesion size with a concomitant improvement in lesion stability indicated by fewer macrophages and more collagen content. Chicory consumption suppressed aortic cholesterol accumulation and intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 expression, whereas it increased aortic ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) expression. Furthermore, chicory consumption improved peritoneal macrophage phenotype with less cellular cholesterol associated with an enhancement of cholesterol efflux capacity through upregulation of ABCA1 and ABCG1, less cellular oxidative stress associated with an inhibition of nicotinamide adenine dinucleotide phosphate oxidase activity, and weaker inflammatory responses associated with an inhibition of nuclear factor-κB activation. Interestingly, ABCA1 and ABCG1 silencing tended to completely block beneficial effects of chicory in peritoneal macrophages. CONCLUSION: Chicory exerts an atheroprotective role in mice possibly by regulating lesional macrophage content and phenotype, suggesting that chicory is one underrated contributor to Mediterranean Diet-induced atheroprotection.