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OBJECTIVE: Socioeconomic status (SES) has been previously associated with children's early development, health, and nutrition; however, evidence about the potential role of caregiver-child interaction in such associations was limited. This study aimed to explore the effect of caregiver-child interaction on the associations of SES with child developmental outcomes, including early neurodevelopment and social-emotional behavior. METHODS: A cross-sectional survey was conducted among 2078 children aged 0-6 in a rural county that just lifted out of poverty in 2020 in Central China. The Ages & Stages Questionnaires-Chinese version (ASQ-C) and the Social-Emotional (ASQ: SE) questionnaire were used to assess children's early neurodevelopment and social-emotional behavior, respectively. Caregiver-child interaction was evaluated with the Brigance Parent-Child Interactions Scale. Regression-based statistical mediation and moderation effect were conducted with the PROCESS macro of SPSS. RESULTS: Children with low SES had an increased risk of suspected neurodevelopmental delay [OR = 1.92, 95% CI: 1.50, 2.44] and social-emotional developmental delay [OR = 1.31, 95% CI: 1.04, 1.66]. The caregiver-child interaction partially mediated the associations of SES with child developmental outcomes; the proportion of the indirect effect was 14.9% for ASQ-C total score and 32.1% for ASQ: SE score. Moreover, the caregiver-child interaction had a significant moderation effect on the association of SES with ASQ-C total score (P < 0.05). A weaker association was observed in children with high-level caregiver-child interaction than in medium and low ones. Similar moderating effects were found among boys but not girls. CONCLUSION: Caregiver-child interaction plays a vital role in the relationship between SES and child development. Children with low SES households will benefit more in terms of their early development from intervention programs strengthening caregiver-child interaction.
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Cuidadores , Desenvolvimento Infantil , População Rural , Classe Social , Humanos , China , Masculino , Feminino , Estudos Transversais , Pré-Escolar , População Rural/estatística & dados numéricos , Lactente , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Criança , Inquéritos e Questionários , Recém-Nascido , Relações Pais-FilhoRESUMO
INTRODUCTION: Previous studies have demonstrated that both family dysfunction and internet addiction (IA) are associated with a higher risk of adolescent depression. However, no study has yet investigated the mechanisms involved. This study aims to explore the mediation and interaction roles of internet addiction (IA) between family functioning and depressive symptoms among adolescents in rural China. METHODS: A multi-stage, stratified cluster, and random sampling was conducted among 3343 adolescents in rural China from October 27 to November 6, 2020. Depressive symptoms, IA, and family functioning were assessed using the Epidemiologic Studies Depression Scale (CESD), the Internet Addiction Test (IAT), and the Family Adaptation Partnership Growth Affection and Resolve Index (APGAR), respectively. Correlation analysis was performed by binary logistic regression. The study employed a four-way decomposition method to explore the potential mechanisms of family functioning on depressive symptoms. RESULTS: The results indicated that family functioning and IA were associated with adolescents' depressive symptoms. The interaction between family functioning and IA accounted for 74 % of the association between family functioning and depression symptoms, while direct effects accounted for 24 %. The "proportion eliminated" (76.11 %) was substantially larger than "proportion mediated" (7.36 %). LIMITATIONS: The cross-sectional design limited to identify the causal relationship among the variables. CONCLUSIONS: We found that family dysfunction synergizes with IA to contribute to the high risk of adolescent depression. Prioritizing at preventing IA in adolescence could be an effective way to mitigate the adverse effects of family dysfunction on depression.
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Depressão , Transtorno de Adição à Internet , Humanos , Adolescente , Masculino , Feminino , Transtorno de Adição à Internet/epidemiologia , Transtorno de Adição à Internet/psicologia , China/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Estudos Transversais , População Rural/estatística & dados numéricos , Relações Familiares , Família/psicologia , Comportamento do Adolescente/psicologiaRESUMO
OBJECTIVES: This study aimed to understand the early development and nurturing care environment of children aged 0-6 years in rural China and to evaluate the sex- and age-specific associations of nurturing care environment with child developmental outcomes. METHODS: A cross-sectional survey involving 2078 children aged 0-6 years was conducted using a stratified cluster sampling strategy. We used face-to-face interviews to collect information on child, family and nurturing care. The Ages & Stages Questionnaires-Chinese version and ASQ: Social-Emotional were applied to assess children's neuro- and social-emotional development, respectively. Lower neurodevelopmental scores indicate an increased risk for neurodevelopmental delay, and higher social-emotional scores are indicative to a risk of social-emotional problems. The multiple linear regression model examined the associations of nurturing care environments with childhood development. RESULTS: Among the investigated children, the average age was (42.9 ± 19.8) months and 55.8% were boys; 67.9% of the children had absent fathers because of labour migration and 54.0% had limited access to books and toys. Overall, boys had a lower total neurodevelopmental score than girls; similar gender patterns were also found in the domains of communication, fine motor, problem-solving and person-social. Concurrent absent fathers and limited access to books and toys were significantly associated with reduced neurodevelopmental scores [ß - 11.44, 95% CI (-18.20, -4.68)] and increased social-emotional developmental scores [ß 5.88, 95%CI (1.35, 10.41)] after controlling for confounding factors. Sex-specific analysis only echoed the results in boys. Additionally, having an absent father and limited access to books and toys was associated with lower neurodevelopmental scores [ß - 14.58, 95%CI (-25.41, -3.75)] in children under 3 years of age and higher social-emotional developmental scores among children aged 3-6 years [ß 10.66, 95%CI (5.09, 16.24)]. CONCLUSIONS: Children, especially boys, with absent fathers due to labour migration have poorer neuro- and social-emotional development. Limited access to books and toys and father absence are linked to the children's developmental delay, especially for those under 3 years of age. Our findings suggest that intervention programs in resource-constrained rural areas are desirable; more importantly, such programs should begin before 3 years of age to achieve a benefit-cost outcome.
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Desenvolvimento Infantil , Deficiências do Desenvolvimento , Criança , Masculino , Feminino , Humanos , Pré-Escolar , Lactente , Estudos Transversais , China , Livros , Pai , PobrezaRESUMO
OBJECTIVE: This paper utilized a person-centered approach to examine whether sleep patterns on school and free days are associated with obesity risk in preschool children aged 3-6 years. METHODS: The cross-sectional analysis included 204 children from the Wuhan Healthy Start Project with valid sleep data in at least four consecutive days gathered via Actigraph GT3X+. Based on three domains of sleep duration, sleep onset, and sleep offset, we used latent profile analysis to identify distinct sleep patterns on school and free days separately. Additionally, we conducted latent transition analysis to explore the probabilities of sleep patterns transitions between school and free days. The multivariate logistic regression model investigated the associations of sleep patterns with overweight/obesity (OWO) (BMI ≥ age- and sex-specific 85th percentile) and abdominal obesity (AO) (WC ≥ age- and sex-specific 75th percentile). RESULTS: Two sleep patterns were identified for school days: "EL-sc" (early-to-sleep/longer-duration) (n = 119; 58.3%) and "LS-sc" (late-to-sleep/shorter-duration) (n = 85; 41.7%). Similarly, "LES-fr" (late-to-sleep/early-to-wake/shorter-duration) (n = 118; 57.8%) and "ELL-fr" (early-to-sleep/late-to-wake/longer-duration) (n = 86; 42.2%) patterns were identified for free days. LTA categorized the participants into four distinct transition groups, i.e., "EL-scâELL-fr" (32.9%), "EL-scâLES-fr" (24.0%), "LS-scâLES-fr" (33.8%), and "LS-scâELL-fr" (9.3%). Compared with the "ELscâELL-fr", the "LS-scâLES-fr" had a higher risk of OWO (AOR 4.76; 95% CI: 1.39-20.33) and AO (AOR, 2.78; 95% CI, 1.21-6.62), respectively. Neither "EL-scâLES-fr" (AOR, 1.11; 95% CI, 0.14-6.67) nor "LS-scâELL-fr" (AOR, 0.74; 95% CI, 0.03-6.14) was significantly associated with OWO. Likewise, no significant association was observed for "EL-scâLES-fr" (AOR, 0.96; 95% CI, 0.35-2.62) and "LS-scâELL-fr" (AOR, 0.56; 95% CI, 0.11-2.18) with AO. CONCLUSIONS: "LS-scâLES-fr" pattern is significantly associated with an increased risk of general and abdominal obesity, indicating its obesogenic nature. Furthermore, although not statistically associated with obesity outcomes, "LS-scâELL-fr" and "EL-scâLES-fr" patterns exhibit a semi-obesogenic characteristic. In addition, we identified a concerning trend that preschool children are at risk of transitioning to and persisting in sleep patterns characterized by delayed and shorter sleep. These findings underscore the importance of implementing interventions and strategies to address sleep patterns as a crucial step to minimize the risk of obesity.
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População do Leste Asiático , Obesidade Abdominal , Obesidade Infantil , Sono , Pré-Escolar , Feminino , Humanos , Masculino , Índice de Massa Corporal , Estudos Transversais , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/etiologia , Sobrepeso/epidemiologia , Sobrepeso/etiologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/etiologiaRESUMO
The effects of air pollutants on psychological health have attracted increasing attention worldwide. However, there is limited evidence on the association between air pollution and children's psychological development. This study explores the association between short- and long-term exposures to air pollutants and children's internalizing and externalizing behaviors. A total of 2303 children of 4-7 years were included in this study. We assessed their behavior using the Child Behavior Checklist (4-16 years). The prevalence of internalizing and externalizing behavior was 4.77% and 4.43%, respectively. For short-term exposure, CO pollution was associated with children's internalizing behaviors, with each 1 mg/m3 increment leading to an odds ratio (OR) of 1.063 (95% CI 1.005, 1.124), 1.065 (95% CI 1.009, 1.124), 1.067 (95% CI 1.007, 1.131), and 1.122 (95% CI 1.018, 1.236) at lag04, lag05, lag06, and lag0120, respectively. O3 (per 1 g[Formula: see text]/m3) was negatively associated with internalizing problems at lag2 [OR = 0.991 (95% CI 0.983, 0.999)]. NO2 (per 1 g[Formula: see text]/m3) was significantly associated with externalizing behaviors, with the ORs of 1.067 (95% CI 1.024, 1.111) at lag060 and 1.060 (95% CI 1.010, 1.113) at lag0120. For long-term exposure, it indicated that 1-year exposure to CO (per 1 mg/m3) and PM2.5 (per 1 g[Formula: see text]/m3) was positively associated with internalizing behavioral risk [OR = 1.724 (95% CI 1.187, 2.504); PM2.5: OR = 1.236 (95% CI 1.114, 1.371)], whereas NO2 (per 1 g[Formula: see text]/m3) exposure was associated with an increased risk of externalizing behavior [OR = 1.123 (95% CI 1.003, 1.256)]. In addition, the interaction analysis showed that boys were at a higher risk of abnormal behaviors associated with long-term exposure to CO, PM2.5, and NO2. Our findings reveal a potential link between air pollution exposure and abnormal behaviors in kindergarten children after short-/long-term exposure, which is an essential supplement to the studies on the association between air pollution and children's behavioral problems.
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Poluentes Atmosféricos , Poluição do Ar , Comportamento Problema , Masculino , Humanos , Criança , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio/análise , Poluição do Ar/análise , Material Particulado/análise , Exposição Ambiental/análiseRESUMO
BACKGROUND: Epigenome-wide association studies have identified some DNA methylation sites associated with body mass index (BMI) or obesity. Studies in the Asian population are lacking. OBJECTIVE: To examine the association of cord blood genome-wide DNA methylation (GWDm) changes with maternal pre-pregnancy BMI and children's BMI-z score at preschool age. Additionally, we also explored the genome-wide differentially methylated regions and differentially methylated probes between preschoolers with overweight/obesity and normal-weight counterparts. METHODS: This two-stage study design included (1) a GWDm analysis of 30 mother-child pairs from 633 participants of the Zhuhai birth cohort with data on newborn cord blood, maternal pre-pregnancy BMI, and children's BMI at 3 years of age; and (2) a targeted validation analysis of the cord blood of ten children with overweight/obesity and ten matched controls to validate the CpG sites. RESULTS: In the first stage, no significant CpG sites were found to be associated with children's BMI-z score at preschool age after FDR correction with the p-values of the CpG sites in FOXN3 (cg23501836) and ZNF264 (cg27437574) being close to 1 × 10-6 . In the second stage, a significant difference of CpG sites in AHRR (chr5:355067-355068) and FOXN3 (chr14: 89630264-89630272 and chr14: 89630387-89630388) was found between the ten children with overweight/obesity and ten controls (p < 0.05). The CpG sites in FOXN3 (chr14:89630264-89630272 and chr14:89630295-89630296) and ZNF264 (chr19: 57703104-57703107 and chr19: 57703301-57703307) were associated with children's BMI-z score; and the CpG sites in FOXN3 (chr14: 89630264-89630272 and chr14: 89630387-89630388) were associated with maternal pre-pregnancy BMI. CONCLUSIONS: DNA methylation in FOXN3 and AHRR is associated with overweight/obesity in preschool-aged children, and the methylation in FOXN3 and ZNF264 might be associated with children's BMI-z score. FOXN3 methylation may be associated with maternal pre-pregnancy BMI, suggesting its potential role in the children's BMI-z score or overweight/obesity. Our results provide novel insights into the mechanisms of children's obesity.
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Metilação de DNA , Sobrepeso , Recém-Nascido , Gravidez , Feminino , Pré-Escolar , Humanos , Índice de Massa Corporal , Sobrepeso/epidemiologia , Sobrepeso/genética , Sobrepeso/metabolismo , Metilação de DNA/genética , Epigenoma , Sangue Fetal/metabolismo , Obesidade/epidemiologia , Obesidade/genética , Obesidade/metabolismoRESUMO
Objective: To examine the birth and health outcomes of children migrating with parents internationally and domestically, and to identify whether the healthy migration effect exist in migrant children. Methods: Five electronic databases were searched for cross-sectional, case-control, or cohort studies published from January 1, 2000 to January 30, 2021and written by English language, reporting the risk of health outcomes of migrant children (e.g., birth outcome, nutrition, physical health, mental health, death, and substance use) We excluded studies in which participants' age more than 18 years, or participants were forced migration due to armed conflict or disasters, or when the comparators were not native-born residents. Pooled odd ratio (OR) was calculated using random-effects models. Results: Our research identified 10,404 records, of which 98 studies were retrained for analysis. The majority of the included studies (89, 91%) focused on international migration and 9 (9%) on migration within country. Compared with native children, migrant children had increased risks of malnutrition [OR 1.26 (95% CI 1.11-1.44)], poor physical health [OR 1.34 (95% CI 1.11-1.61)], mental disorder [OR 1.24 (95% CI 1.00-1.52)], and death [OR 1.11 (95% CI 1.01-1.21)], while had a lower risk of adverse birth outcome [OR 0.92 (95% CI 0.87-0.97)]. The difference of substance use risk was not found between the two groups. Conclusion: Migrant children had increased risk of adverse health outcomes. No obvious evidence was observed regarding healthy migration effect among migrant children. Actions are required to address the health inequity among these populations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier: CRD42021214115.
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Low-temperature decomposition of supersaturated solid solution into unfavorable intergranular precipitates is a long-standing bottleneck limiting the practical applications of nanograined aluminum alloys that are prepared by severe plastic deformation. Minimizing the vacancy concentration is generally regarded as an effective approach in suppressing the decomposition process. Here we report a counterintuitive strategy to stabilize supersaturated solid solution in nanograined Al-Cu alloys via high-density vacancies in combination with Sc microalloying. By generating a two orders of magnitude higher concentration of vacancies bonded in strong (Cu, Sc, vacancy)-rich atomic complexes, a high thermal stability is achieved in an Al-Cu-Sc alloy that precipitation is nearly suppressed up to ~230 °C. The solute-vacancy complexes also enable the nanograined Al-Cu alloys with higher strength, greater strain hardening capability and ductility. These findings provide perspectives towards the great potentials of solute-vacancy interaction and the development of nanograined alloys with high stability and well-performed mechanical properties.
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Previous studies have supported the link between children's self-regulation (CSR) and weight status, but the potential pathways have not been elucidated yet. We aimed to investigate whether and to what extent health behaviors mediate this association, as well as to explore the sex effect. For this study, we recruited 3740 preschoolers in Wuhan, China. The height and weight of children were measured, and a body mass index of the ≥85th percentile was defined as overweight/obesity (OWO). We used the Children's Behavior Questionnaire, with measured domains including inhibitory control, impulsivity, anger, and attentional focusing, to assess CSR. The primary caregivers' SR (PSR) was assessed with the Self-Control Scale. Information on lifestyles collected from questionnaires was utilized to construct the health behavior index (HBI). We found that Children's HBI was associated with both CSR and PSR, inhibitory control (OR = 0.81, p < 0.001), anger (OR = 1.23, p < 0.001), attentional focusing (OR = 0.70, p < 0.001), impulsivity (OR = 1.23, p < 0.001), and PSR (OR = 0.73, p < 0.001). Children's impulsivity was associated with their OWO (OR = 1.11, p = 0.013) which was partly mediated by the HBI (direct effect: ß = 0.092, p = 0.026; indirect effect: ß = 0.011, p = 0.007). The sex-specific analysis indicated that this mediation effect was only significant in boys. These results indicated that impulsivity is associated with childhood weight status, which is partially mediated by health behaviors, especially in boys.
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Comportamento Infantil , Autocontrole , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Comportamento Alimentar , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Obesidade , Sobrepeso , Inquéritos e QuestionáriosRESUMO
BACKGROUND: An earlier meta-analysis of genome-wide association studies in Asian populations detected five novel body mass index-associated single-nucleotide polymorphisms (SNPs), including potassium voltage-gated channel subfamily Q member 1 (KCNQ1) (rs2237892), ALDH2/MYL2 (rs671, rs12229654), ITIH4 (rs2535633), and NT5C2 (rs11191580). Whether these SNPs take effect in early life, for example, affect infant rapid weight gain (RWG), is unclear. METHODS: We obtained genomic DNA from 460 term infants with normal birth weight. RWG was defined as the change of weight-for-age standardized Z-score, calculated according to the Children Growth Standard released by the World Health Organization, from birth to 3 months of age >0.67. Using genetic models, associations between the candidate SNPs and infant RWG were examined, along with the interaction between the SNPs and the potential risk factors. RESULTS: RWG was presented in 225 of 460 infants. SNP rs2535633 and rs2237892 were associated with the risk of RWG. Both additive and multiplicative interaction effects were found between infant delivery mode and rs2237892. The negative association between the rs2237892 T allele and infant RWG was only observed in vaginally delivered infants. CONCLUSIONS: Obesity-related loci rs2535633 and rs2237892 are associated with infant RWG in the first 3 months of infancy. The relationship between rs2237892 and infant RGW might be moderated by cesarean delivery. IMPACT: Genetic predisposition is an essential aspect to understand infant weight gain. Obesity-related SNPs, rs2535633 and rs2237892, are associated with RWG in very early years of life. The negative association between rs2237892 T allele and RWG is only observed in infants delivered vaginally instead of cesarean section.
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Estudo de Associação Genômica Ampla , Canal de Potássio KCNQ1 , Aldeído-Desidrogenase Mitocondrial/genética , Cesárea , Criança , Feminino , Humanos , Lactente , Canal de Potássio KCNQ1/genética , Obesidade , Polimorfismo de Nucleotídeo Único , Gravidez , Proteínas Secretadas Inibidoras de Proteinases/genética , Aumento de Peso/genéticaRESUMO
OBJECTIVE: The aim of this study was to explore the potential impact of maternal gestational weight gain (GWG), infant birth weight, and postnatal weight change (ΔWAZ) on the relationship between maternal prepregnancy BMI (ppBMI) and childhood BMI. METHODS: This retrospective cohort study analyzed a data set from Wuhan, China. The mediation effect of targeted mediators on the association between maternal BMI and childhood BMI at the age of 2 years was analyzed. RESULTS: In the mediation model comprising maternal GWG, infant birth weight, and the first-6-month ΔWAZ as mediators of the association between ppBMI and children's BMI, the per unit increase in ppBMI resulted in a 0.01-kg/m2 increase in children's BMI, through all three mediators. For the model comprising infant birth weight and the first-6-month ΔWAZ as mediators but maternal GWG as a moderator, the indirect effects of the first-6-month ΔWAZ on the relationship between ppBMI and childhood BMI was 0.0018 higher when maternal GWG increased from average values to 1 SD above the average values. CONCLUSIONS: Maternal GWG, infant birth weight, and the first-6-month ΔWAZ mediated the effects of maternal ppBMI on children's BMI. Interventions targeting these factors can mitigate the risk of childhood obesity.
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Análise de Mediação , Obesidade Infantil , Índice de Massa Corporal , Criança , Pré-Escolar , Humanos , Lactente , Obesidade Infantil/epidemiologia , Estudos Retrospectivos , Aumento de PesoRESUMO
The associations between socioeconomic status and childhood overweight/obesity are inconsistent, and potential underlying factors are unclear. In China, Hukou status is an important attribute of individual's socioeconomic circumstances, but previously received less consideration as a socioeconomic indicator. This study aimed to investigate the association between comprehensive socioeconomic status and childhood overweight/obesity. Using data from Wuhan Maternal and Child Health Management Information System (2009-2018, N = 209,500), clustering analysis was used to create comprehensive socioeconomic groups with indicator components such as parental education level, occupation, and maternal Hukou. The associations between the determined socioeconomic status and childhood overweight/obesity at age 1 and 2 were examined by log-binomial model. Parallel and serial mediation analyses were performed to test the indirect effects of potential mediators, including maternal pre-pregnancy body mass index, gestational weight gain, and infant birth weight, in the association between socioeconomic status and childhood overweight/obesity. Four clusters, defined as low, low-medium, medium-high, and high socioeconomic groups, were identified through clustering analysis. Hukou, among five socioeconomic components, contributed the most to the development of childhood overweight/obesity. Children in the low-medium socioeconomic group have a greater risk of overweight/obesity than the low socioeconomic group. Indirect effects of maternal pre-pregnancy body mass index, gestational weight gain, and infant birth weight were identified for the association. In conclusion, socioeconomic status may impact childhood obesity through maternal pre-pregnancy body mass index, gestational weight gain, and infant birth weight. Hukou should be considered in the evaluation of socioeconomic status in China.
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Obesidade Infantil , Peso ao Nascer , Índice de Massa Corporal , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Gravidez , Fatores de Risco , Classe SocialRESUMO
BACKGROUND/OBJECTIVES: Few studies have examined the effects of the weight status at birth and preschool age on the risk of elevated blood pressure (EBP) in early childhood, and whether the effects can be modified by breastfeeding duration remains unclear. We aimed to evaluate the effects of high birth weight (HBW) with overweight/obese or abdominal obesity on the risk of EBP in preschoolers, and further evaluate the effects classified by breastfeeding duration (<6 and ≥6 months). SUBJECTS/METHODS: This cross-sectional study was conducted in 2018 in Zhuhai, China. Out of 2390 3-4-year-old preschoolers originally recruited, a total of 1899 were included in the analysis. Logistic regression analysis was performed to examine the effects of the weight status at the two age points and breastfeeding duration on the risk of EBP. RESULTS: Preschoolers with current overweight/obese had a 1.13-fold increased risk of EBP than those with persistent normal weight, irrespective of their birth weight. However, the preschoolers with HBW had no increased risk of EBP, when they became normal weight (OR 1.70, 0.78-3.72). Similar results were found for the current abdominal obesity and the risk of EBP. In addition, the EBP risk of obese status was minimized if preschoolers were breastfed for ≥6 months. CONCLUSIONS: Obesity status at preschool age can increase the risk of EBP, irrespective of birth weight. However, this EBP risk can be mitigated if HBW changes to current normal weight. Longer breastfeeding duration can partially offset the risk of EBP in preschoolers with obesity status.
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Aleitamento Materno , Sobrepeso , Peso ao Nascer , Pressão Sanguínea , Índice de Massa Corporal , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Sobrepeso/epidemiologia , Fatores de RiscoRESUMO
PURPOSE: To find the lowest effective dose of verteporfin in the treatment of acute central serous chorioretinopathy with photodynamic therapy (PDT). METHODS: Patients with acute central serous chorioretinopathy were chosen and treated with PDT with verteporfin. Decreasing doses of verteporfin were applied to the first 7 patients at 70%, 60%, 50%, 40%, 30%, 20%, and 10% of the full dose (6 mg/m). Other patients were treated with the effective lowest dose (30% of full dose). Fluorescein angiography, indocyanine green angiography, and optical coherence tomography recordings were performed before PDT and at 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, and 12 months after PDT. The pretreatment and posttreatment best-corrected visual acuity were compared. RESULTS: Fifteen eyes of 15 patients with the diagnosis of acute central serous chorioretinopathy were chosen and treated with PDT. The results at each dose suggested that 30% of the full dose of verteporfin was the lowest effective dose. The mean improvement in visual acuity was 4.1 +/- 0.25 lines at follow-up (mean 11.8 months). No complications were found during observation, except 1 patient at 70% dose who developed retinal angiomatous proliferation at the 1-month follow-up. CONCLUSION: On the basis of the results of this study and available information regarding the expected rate of spontaneous resolution, 30% verteporfin dose seems to be safe and effective in the treatment of acute central serous chorioretinopathy.
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Coriorretinopatia Serosa Central/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Doença Aguda , Adulto , Idoso , Coriorretinopatia Serosa Central/patologia , Coriorretinopatia Serosa Central/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/efeitos adversos , Porfirinas/efeitos adversos , Retina/efeitos dos fármacos , Retina/patologia , Resultado do Tratamento , Verteporfina , Acuidade VisualRESUMO
The purpose of this work was to investigate the effect of c-fos antisense oligonucleotide (c-fos-AS-ON) on proliferative vitreoretinopathy (PVR). Cultures of human retinal pigment epithelial (hRPE) cells were established from adult human corneal donors. These cells were positively stained for cytokeratins. C-fos-AS-ON effect on serum-stimulated cell proliferation was estimated by evaluating the incorporation of 5-bromo-2'-deoxy-uridine (BrdU) into cellular DNA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were respectively performed to quantify the serum-stimulated c-fos gene mRNA and protein expression in hRPE cells. Eight rabbits (16 eyes) were divided into c-fos-AS-ON treatment group and control group. 2.5 x 10(5) cultured hRPE cells were injected into the vitreous cavity of eyes to establish a PVR model. Prevalence of PVR and retinal detachment were determined by indirect ophthalmoscopy on days 1, 3, 7, 14, 21 and 28 post-injection and by pathological study on days 28 post-injection. The results showed that blocking the expression of c-fos by the addition of c-fos-AS-ON to the culture medium significantly inhibited the hRPE cells proliferation. This effect of c-fos-AS-ON was found to be sequence specific (the use of a sense or a mismatch sense oligonucleotide had no such an effect) and dose-dependent (0.375 microM was the lowest effective dose tested). Growth inhibition by c-fos-AS-ON remained for at least 72 h. By using RT-PCR and Western blotting, we found that the c-fos-AS-ON could specifically inhibit c-fos mRNA and protein synthesis in cultured hRPE cells. Though the eyes injected with c-fos-AS-ON also developed features of PVR, the severities of days 14, 21 and 28 post-injection were significantly lower than those in the control eyes (P<0.05). We conclude that c-fos-AS-ON can inhibit cultured hRPE cell proliferation, which mechanism may relate to blocking the expression of c-fos and can reduce the prevalence of experimental PVR. These findings establish a rationale for investigating the potential use of a c-fos-AS-ON as a novel therapeutical tool in the treatment of PVR.
Assuntos
Genes fos/genética , Terapia Genética/métodos , Oligonucleotídeos Antissenso , Epitélio Pigmentado Ocular/patologia , Vitreorretinopatia Proliferativa/patologia , Animais , Western Blotting , Proliferação de Células , Células Cultivadas , Progressão da Doença , Marcação de Genes/métodos , Humanos , Queratinas/metabolismo , Masculino , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/genética , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transfecção , Vitreorretinopatia Proliferativa/prevenção & controleRESUMO
AIM: To investigate the protective mechanisms of Weikang (WK) decoction on gastric mucosae. METHODS: Ninety rats were randomly divided into nine groups of 10 each, namely group, model group, group with large WK dosage, group with medium WK dosage, group with small WK dosage, group with herbs of jianpiyiqi (strengthening the spleen and replenishing qi), group with herbs of yangxuehuoxue (invigorating the circulation of and nourishing the blood), group with herbs of qingrejiedu (clearing away the heat-evils and toxic materials), group with colloidal bismuth pectin (CBP) capsules. According to the method adopted by Yang Xuesong, except normal control group, chronic gastric ulcer was induced with 100% acetic acid. On the sixth day after moldmaking, WK decoction was administered, respectively at doses of 20, 10 and 5 g/kg to rats of the WK groups, or the groups with herbs of jianpiyiqi, yangxuehuoxue and qingrejiedu, 10 mL/kg was separately administered to each group every day. For the group with CBP capsules, medicine was dissolved with water and doses 15 times of human therapeutic dose were administered (10 mL/kg solution containing 0.35% CBP). Rats of other groups were fed with physiological saline (10 mL/kg every day). Administration lasted for 16 d. Rats were killed on d 22 after mold making to observe changes of gastric mucosa. The mucus thickness of gastric mucosa surface was measured. Levels of epidermal growth factor (EGF) in gastric juice, nitric oxide (NO) in gastric tissue, endothelin (ET) in plasma, superoxide dismutase (SOD) in plasma, malondialdehyde (MDA) in plasma and prostaglandin I(2) (PGI(2)) were examined. RESULTS: Compared with control group, ulceration was found in gastric mucosa of model group rats. The mucus thickness of gastric mucosa surface, the levels of EGF, NO, 6-K-PGF(1)alpha and SOD decreased significantly in the model group (EGF: 0.818+/-0.18 vs 2.168+/-0.375, NO: 0.213+/-0.049 vs 0.601+/-0.081, 6-K-PGF(1)alpha: 59.7+/-6.3 vs 96.6+/-8.30, SOD: 128.6+/-15.0 vs 196.6+/-35.3, P<0.01), the levels of ET (179.96+/-37.40 vs 46.64+/-21.20, P<0.01) and MDA (48.2+/-4.5 vs 15.7+/-4.8, P<0.01) increased. Compared with model group, the thickness of regenerative mucosa increased, glandular arrangement was in order, and cystic dilative glands decreased, while the mucus thickness of gastric mucosa surface increased (20 g/kg WK: 51.3+/-2.9 vs 23.2+/-8.4, 10 g/kg WK: 43.3+/-2.9 vs 23.2+/-8.4, 5 g/kg WK: 36.1+/-7.2 vs 23.2+/-8.4, jianpiyiqi: 35.4+/-5.6 vs 23.2+/-8.4, yangxuehuoxue: 33.1+/-8.9 vs 23.2+/-8.4, qingrejiedu: 31.0+/-8.0 vs 23.2+/-8.4 and CBP: 38.2+/-3.5 vs 23.2+/-8.4, P<0.05-0.01). The levels of EGF (20 g/kg WK: 1.364+/-0.12 vs 0.818+/-0.18, 10 g/kg WK: 1.359+/-0.24 vs 0.818+/-0.18, 5 g/kg WK: 1.245+/-0.31 vs 0.818+/-0.18, jianpiyiqi: 1.025+/- 0.45 vs 0.818+/-0.18, yangxuehuoxue: 1.03+/-0.29 vs 0.818+/-0.18, qingrejiedu: 1.02+/-0.47 vs 0.818+/-0.18 and CBP: 1.237+/-0.20 vs 0.818+/-0.18, P<0.05-0.01), NO (20 g/kg WK: 0.480+/-0.026 vs 0.213+/-0.049, 10 g/kg WK: 0.390+/-0.055 vs 0.213+/-0.049, 5 g/kg WK: 0.394+/-0.026 vs 0.213+/-0.049, jianpiyiqi: 0.393+/-0.123 vs 0.213+/-0.049, yangxuehuoxue: 0.463+/-0.077 vs 0.213+/-0.049, qingrejiedu: 0.382+/-0.082 vs 0.213+/-0.049 and CBP: 0.395+/-0.053 vs 0.213+/-0.049, P<0.05-0.01), 6-K-PGF(1)alpha (20 g/kg WK: 86.8+/-7.6 vs 59.7+/-6.3, 10 g/kg WK: 77.9+/-7.0 vs 59.7+/-6.3, 5 g/kg WK: 70.0+/-5.4 vs 59.7+/-6.3, jianpiyiqi: 73.5+/-12.2 vs 59.7+/-6.3, yangxuehuoxue: 65.1+/-5.3 vs 59.7+/-6.3, qingrejiedu: 76.9+/-14.6 vs 59.7+/-6.3, and CBP: 93.7+/-10.7 vs 59.7+/-6.3, P<0.05-0.01) and SOD (20 g/kg WK: 186.4+/-19.9 vs 128.6+/-15.0, 10 g/kg WK: 168.2+/-21.7 vs 128.6+/-15.0, 5 g/kg WK: 155.6+/-21.6 vs 128.6+/-15.0, jianpiyiqi: 168.0+/-85.3 vs 128.6+/-15.0, yangxuehuoxue: 165.0+/-34.0 vs 128.6+/-15.0, qingrejiedu: 168.2+/-24.9 vs 128.6+/-15.0, and CBP: 156.3+/-18.1 vs 128.6+/-15.0, P<0.05-0.01) significantly increased. The levels of ET (20 g/kg WK: 81.30+/-17.20 vs 179.96+/-37.40, 10 g/kg WK: 83.40+/-25.90 vs 179.96+/-37.40, 5 g/kg WK: 93.87+/-20.70 vs 179.96+/-37.40, jianpiyiqi: 130.67+/-43.66 vs 179.96+/-37.40, yangxuehuoxue: 115.88+/-34.09 vs 179.96+/-37.40, qingrejiedu: 108.22+/-36.97 vs 179.96+/-37.40, and CBP: 91.96+/-19.0 vs 179.96+/-37.40, P<0.01) and MDA (20 g/kg WK: 21.6+/-7.4 vs 48.2+/-4.5, 10 g/kg WK: 32.2+/-7.3 vs 48.2+/-4.5, 5 g/kg WK: 34.2+/-6.2 vs 48.2+/-4.5, jianpiyiqi: 34.9+/-13.8 vs 48.2+/-4.5, yangxuehuoxue: 35.5+/-16.7 vs 48.2+/-4.5, qingrejiedu: 42.2+/-17.6 vs 48.2+/-4.5, and CBP: 30.1+/-6.1 vs 48.2+/-4.5, P<0.05-0.01) obviously decreased. The 20 g/kg WK group was better than 10 g/kg (the mucus thickness: 51.3+/-2.9 vs 43.3+/-2.9, NO: 0.480+/-0.026 vs 0.390+/-0.055, SOD: 186.4+/-19.9 vs 168.2+/-21.7, P<0.01) and 5 g/kg (the mucus thickness: 51.3+/-2.9 vs 36.1+/-7.2, NO: 0.480+/-0.026 vs 0.394+/-0.026, SOD: 186.4+/-19.9 vs 155.6+/-21.6, P<0.01) groups and CBP group (the mucus thickness: 51.3+/-2.9 vs 38.2+/-3.5, NO: 0.480+/-0.026 vs 0.395+/-0.053, SOD: 186.4+/-19.9 vs 156.3+/-18.1, P<0.01) in the mucus thickness, NO and SOD levels and better than 10 g/kg (86.8+/-7.6 vs 77.9+/-7.0, P<0.05) and 5 g/kg (86.8+/-7.6 vs 70.0+/-5.4, P<0.05) groups in 6-K-PGF(1)alpha level, 10 g/kg WK group was better than 5 g/kg WK (the mucus thickness: 43.3+/-2.9 vs 36.1+/-7.2, P<0.01, SOD: 168.2+/-21.7 vs 155.6+/-21.6, P<0.05) and CBP groups (the mucus thickness: 43.3+/-2.9 vs 38.2+/-3.5, P<0.01, SOD: 168.2+/-21.7 vs 156.3+/-18.1, P<0.05) in the mucus thickness and SOD level. In compound group, jianpiyiqi group, yangxuehuoxue group, qingrejiedu group, the level of ET was decreased, NO contents were increased in gastric tissue of ulcers in rats. CONCLUSION: WK decoction and separated recipes have significantly protective effect on ethanol-induced gastric mucosal injury. They can increase the content of EGF in gastric juice, PGI(2) SOD in plasma and NO in gastric tissues, thicken the mucus on the gastric mucosa, and decrease the impairing factor MDA, ET in plasma.