The mediation and interaction effects of Internet addiction in the association between family functioning and depressive symptoms among adolescents: A four-way decomposition.

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.

Mediating role of birth at a baby-friendly hospital in the association between parental socioeconomic status and infant exclusive breastfeeding at six months old.

BACKGROUND: Current evidence suggests that the exclusive breastfeeding (EBF) rate at six months postpartum in China falls considerably below the targets recommended by the World Health Organization (WHO). Socioeconomic disparities in EBF have been observed in developing countries, with significant heterogeneity across studies. Despite the implementation of the Baby-Friendly Hospital Initiative (BFHI) in China since the 1990s to promote breastfeeding, there has been a lack of assessment concerning infants from different socioeconomic backgrounds. This study sought to investigate the association between socioeconomic status (SES) and EBF and explore the potential impact of giving birth at a Baby-Friendly Hospital (BFH) on this association. METHODS: We analyzed data from 98,469 mother-child dyads selected from the Maternal and Child Health Management Information System. We used log-binomial models to examine the relationships between SES and EBF, SES and giving birth at a BFH, as well as BFH births and EBF. Additionally, we explored a counterfactual mediation approach to assess the mediating role of BFH births in the SES-EBF association. FINDINGS: We identified a significant association between SES and EBF (RRMedium vs. Low = 1.47, 95% CI 1.39-1.55; RRHigh vs. Low = 1.40, 95% CI 1.32-1.49). Mothers with higher SES were more likely to give birth at BFHs (RRMedium vs. Low = 1.85, 95% CI 1.81-1.88; RRHigh vs. Low=2.29, 95% CI 2.25-2.33). The significance of the SES-EBF association was attenuated when the type of hospital for childbirth was considered, revealing the significant mediating effect of BFH births in the SES-EBF association. CONCLUSION: Socioeconomic disparities are linked to infant EBF rates, with giving birth at a BFH mediating this association, especially for cases with low SES in rural areas.

Association between short- and long-term exposures to air pollutants and internalizing/externalizing behavior in children aged 4 to 7 years.

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.

Maternal pre-pregnancy body mass index and offspring with overweight/obesity at preschool age: The possible role of epigenome-wide DNA methylation changes in cord blood.

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.

Birth and Health Outcomes of Children Migrating With Parents: A Systematic Review and Meta-Analysis.

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.

The Mediation Role of Health Behaviors in the Association between Self-Regulation and Weight Status among Preschool Children: A Sex-Specific Analysis.

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.

Clinical Effect of Nimodipine Combined with Magnesium Sulfate on Pregnancy-Induced Hypertension Syndrome.

The incidence of pregnancy-induced hypertension in China is 9.4%, which is at a relatively high level. Its serious impact on maternal and infant health is the main reason for maternal and perinatal morbidity and mortality. There are many factors affecting pregnancy-induced hypertension. The incidence of pregnancy-induced hypertension is different due to different levels of cultural knowledge, health awareness, economic income, nutrition, and medical support. Since its etiology has not been elucidated thus far, there is no known treatment of the disease, and the main principles are spasmolysis, hypotension, expansion, and timely termination of pregnancy. Observe the effect of nimodipine combined with magnesium sulfate on serum heat shock protein 70 (HSP70) and pentamer 3 (PTX3) levels in patients with pregnancy-induced hypertension. Ninety-six patients with pregnancy-induced hypertension syndrome admitted to our hospital from May 2016 to February 2019 are selected and randomly divided into two groups according to the 1 : 1 principle, with 48 cases in each group. The single drug group is treated with magnesium sulfate, and the combined group is treated with nimodipine combined with magnesium sulfate. Changes in blood pressure, HSP70, PTX3, placental growth factor (PLGF), and vascular endothelial cell injury markers are recorded in the two groups, and adverse reactions and pregnancy outcomes are observed. After treatment, the blood pressure and levels of HSP70, PTX3, endothelin-1 (ET-1), and nitric oxide (NO) in the two groups decreased, and the level of PLGF increased. The diastolic blood pressure, systolic blood pressure, and levels of HSP70, PTX3, ET-1, and NO in the combined group are lower than those in the single drug group, and the level of PLGF is higher than that in the single drug group (P < 0.05). During the treatment period, the adverse reaction rate of the combined group is 6.25% compared with 8.33% of the single agent group, and the difference is not statistically significant (P > 0.05). Follow-up visits found that the cesarean section rate and abnormal fetal heart rate in the combined group are 16.67% and 4.17%, respectively, which are lower than 35.42% and 16.67% in the single drug group, and the difference is statistically significant (P < 0.05). Compared with 14.58%, 12.50%, and 2.08% in the single drug group, the neonatal asphyxia rate, premature birth rate, and stillbirth rate in the combined group are 6.25%, 4.17%, and 0.00%, respectively, and the difference is not statistically significant (P > 0.05). Nimodipine combined with magnesium sulfate can effectively control blood pressure in patients with pregnancy-induced hypertension, reduce vascular endothelial damage, regulate the expression of HSP70, PTX3, and PLGF, and improve pregnancy outcomes without increasing adverse reactions.

Associations between KCNQ1 and ITIH4 gene polymorphisms and infant weight gain in early life.

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.

Early childhood body mass index trajectory and overweight/obesity risk differed by maternal weight status.

OBJECTIVES: To evaluate the associations of maternal prepregnancy body mass index (pp-BMI) and gestational weight gain (GWG) with the childhood BMI z-score (BMI-z) trajectories from birth to 2 years old and the risk of overweight/obesity (OWO) at 2 years of age. SUBJECTS/METHODS: Mother-child dyads (23,617) were involved in the analysis. They were followed up from early pregnancy to 2 years postpartum with their healthcare data recorded in the Wuhan Maternal and Child Health Management Information System (WMCHMIS). The OWO in children was defined as BMI-z > 1. Linear mixed models (LMM) and unconditional logistic regression were used to evaluate the independent and joint associations of pp-BMI and GWG with the BMI-z trajectory of children per their anthropometric measurements at 0, 1, 3, 6, 9, 12, 18, and 24 months old and the risk of OWO at 2 years of age. RESULTS: Maternal overweight/obesity and excessive GWG independently and jointly increased the risks of their offspring falling into high BMI-z trajectories of birth to 2 years (p < 0.001). In addition, the children whose mothers were overweight/obese before pregnancy and gained excessive weight during pregnancy independently and jointly increased the OWO risk in children at age 2, with adjusted odds ratios (adjOR) of 1.36 (95% CI, 1.22-1.53), 1.28 (95% CI, 1.18-1.39), and 1.76 (95% CI: 1.52-2.03), respectively. CONCLUSIONS: Maternal prepregnancy overweight/obesity and excessive GWG can independently and jointly increase the risks of their children falling into high BMI-z trajectories from birth to 2 years of age and becoming overweight/obese at age 2. Maternal overweight/obesity and excessive gestational weight should be the prime targets for early obese prevention efforts.

Upregulated cyclins may be novel genes for triple-negative breast cancer based on bioinformatic analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the leading causes of death among females around the world. However, the molecular mechanism of the disease among TNBC patients remains to be further studied. METHODS: In our study, four microarray data and two high throughput sequencing data were acquired from the GEO database, and the differentially expressed genes (DEGs) between TNBC and normal tissues had been analyzed. Analysis of functional enrichment and pathway enrichment of DEGs was conducted by the Funrich software, and protein-protein interaction (PPI) network gained from the STRING, and hub genes were confirmed by the Cytoscape. Kaplan-Meier plotter (KM plotter) online dataset had been used to analyze DEGs of overall survival (OS), and progression-free survival (PFS). RESULTS: In total, 1638 DEGs were gained in our study covering 984 upregulated and 654 downregulated genes. Moreover, a PPI network was constructed, and cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), and cyclin A2 (CCNA2) were found as top genes with higher node degrees. CDK1, CCNA2, and CCNB1were obviously enriched in the cell cycle. The top upregulated genes including CDK1, CCNB1, CCNA2, and PLK1 were overexpressed in TNBC, and correlated with worse OS in breast cancer. High expression of CCNB1 was correlated with worse PFS in TNBC (HR = 1.42, 95% CI: 1.04-1.94, P = 0.028). Besides, there was a correlation between CCNB1 and CDK1 in TNBC, as well as between CCNA2 and CDK1 (r = 0.804, P < 0.001; r = 0.577, P < 0.001, respectively). CONCLUSION: Our results suggest that cyclin CDK1, CCNB1, and CCNA2 are overexpressed in TNBC and they could act as novel biomarkers for the diagnosis and treatment of TNBC.

Effectiveness of long-term using statins in COPD - a network meta-analysis.

OBJECTIVES: To evaluate the effectiveness of long-term treatment of statins for chronic obstructive pulmonary disease (COPD), and to answer which one is better. METHODS: General meta-analysis was performed to produce polled estimates of the effect of mortality, inflammatory factors, and lung function index in COPD patients by the search of PubMed, Web of Science, Embase, and China National Knowledge Infrastructure for eligible studies. A network meta-analysis was performed to synthetically compare the effectiveness of using different statins in COPD patients. RESULTS: General meta-analysis showed that using statins reduced the risk of all-cause mortality, heart disease-related mortality and COPD acute exacerbation (AECOPD) in COPD patients, the RR (95% CI) were 0.72 (0.63,0.84), 0.72 (0.53,0.98) and 0.84 (0.79,0.89), respectively. And using statins reduced C-reactive protein (CRP) and pulmonary hypertension (PH) in COPD patients, the SMD (95% CI) were - 0.62 (- 0.52,-0.72) and - 0.71 (- 0.85,-0.57), respectively. Network meta-analysis showed that Fluvastatin (97.7%), Atorvastatin (68.0%) and Rosuvastatin (49.3%) had higher cumulative probability than other statins in reducing CRP in COPD patients. Fluvastatin (76.0%) and Atorvastatin (75.4%) had higher cumulative probability than other satins in reducing PH in COPD patients. CONCLUSIONS: Using statins can reduce the risk of mortality, the level of CRP and PH in COPD patients. In addition, Fluvastatin and Atorvastatin are more effective in reducing CRP and PH in COPD patients.

Overexpression of RASAL1 Indicates Poor Prognosis and Promotes Invasion of Ovarian Cancer.

RAS protein activator like-1 (RASAL1) exists in numerous human tissues and has been commonly demonstrated to act as a tumor suppressor in several cancers. This study aimed to identify the functional characteristics of RASAL1 in ovarian adenocarcinoma and a potential mechanism of action. We analyzed RASAL1 gene expression in ovarian adenocarcinoma samples and normal samples gained from the GEO and Oncomine databases respectively. Then the relationship between RASAL1 expression and overall survival (OS) was assessed using the Kaplan-Meier method. Furthermore, the biological effect of RASAL1 in ovarian adenocarcinoma cell lines was assessed by Quantitative real time-PCR (qRT-PCR), Cell Counting Kit-8 (CCK-8), western blot, wound healing and transwell assay. The statistical analysis showed patients with higher RASAL1 expression correlated with worse OS. The in vitro assays suggested knockdown of RASAL1 could inhibit cell proliferation, cell invasion and migration of ovarian adenocarcinoma. Moreover, the key proteins in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathway were also decreased in ovarian adenocarcinoma cells with RASAL1 silencing. These findings provide promising evidence that RASAL1 may be not only a powerful biomarker but also an effective therapeutic target of ovarian adenocarcinoma.

Effects of acrylonitrile-induced oxidative stress on testicular apoptosis through activation of NF-κB signaling pathway in male sprague dawley rats.

Acrylonitrile (ACN) treatment can induce testicular toxicity in Sprague-Dawley (SD) rats, with the toxicity potentially related to apoptosis, mediated by nuclear factor-κB (NF-κB). The present study investigated the potential role of NF-κB in the induction of apoptosis and testicular toxicity in ACN-treated rats. Adult male SD rats were randomly divided into 3 treatment groups: a control group (corn oil), an ACN group (50 mg/kg) in which ACN was administered by gavage, and an ACN and N-acetylcysteine (ACN+NAC) group. The rats were given NAC (300 mg/kg) 30 min prior to the administration of ACN, and ACN was administered by gavage for 90 days. The ACN treatment markedly increased malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity in the testis. Glutathione (GSH) was significantly depleted in the ACN groups, and the effects of ACN were blocked by the anti-oxidant NAC. The ACN treatment also increased the expression of NF-κB (p65) and phosphorylated-IκB kinase (IKK)-α/ß and decreased the expression of an inhibitor of NF-κB (IκB-α). The pretreatment with NAC significantly inhibited the activation of NF-κB. In addition, the expression of Bax increased after the ACN treatment, and the induction of Bax was abolished by NAC. Taken together, the data suggested that ACN-induced oxidative stress activated the NF-κB signaling pathway, which modulated the expression of Bax and contributed to testicular apoptosis.

Association between the MTHFR A1298C polymorphism and risk of cancer: evidence from 265 case-control studies.

Many molecular, epidemiological studies have been performed to explore the association between MTHFR A1298C polymorphism and cancer risk. However, the results were inconsistent or even contradictory. Hence, we performed a meta-analysis to investigate the association between cancer risk and MTHFR A1298C (81,040 cases and 114,975 controls from 265 studies) polymorphism. Overall, significant association was observed between MTHFR A1298C polymorphism and cancer risk when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly increased cervical cancer (dominant model: OR 1.46, 95 % CI 1.13-1.90; AC vs. AA: OR 1.48, 95 % CI 1.13-1.92) and lymphoma (dominant model: OR 1.22, 95 % CI 1.04-1.44; recessive model: OR 1.66, 95 % CI 1.15-2.39; CC vs. AA: OR 1.75, 95 % CI 1.21-2.53) risk were observed in Asians, and significantly decreased colorectal cancer risk was found in Asians (recessive model: OR 0.75, 95 % CI 0.59-0.96; CC vs. AA: OR 0.77, 95 % CI 0.60-1.00). In summary, this meta-analysis suggests that MTHFR A1298C polymorphism is associated with increased cervical cancer and lymphoma risk in Asians, and MTHFR A1298C polymorphism is associated with decreased colorectal cancer risk in Asians. Moreover, this meta-analysis also points out the importance of new studies, such as oral cancer and chronic myeloid leukemia, because they had high heterogeneity in this meta-analysis (I (2) > 75 %).