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Background: China has seen rapid increase in obesity and hypertension prevalence and fast food consumption over the past decade. We examined status and risk factors for Western- and Chinese fast food consumption and their associations with health outcomes in Chinese children, and examined how maternal factors were associated with child health outcomes.Methods: Data of 1626 students aged 7-16 (11.6 ± 2.0) years and their parents in four mega-cities across China (Beijing, Shanghai, Nanjing, and Xi'an) were collected in the 2015 baseline survey of the Childhood Obesity Study in China Mega-cities. Weight, height, waist circumference, and blood pressure were measured. Food intake was assessed using questionnaire. Mixed models were used to examine the associations.Results: Among the children, 11.1% were obese, 19.7% were centrally obese, and 9.0% had hypertension. Obesity prevalence was much higher in boys than in girls (15.2% vs. 6.9% and 27.4% vs. 11.7%, respectively, both P < 0.001). About half (51.9% and 43.6%) of children consumed Western and Chinese fast food, respectively, over the past 3 months. Compared to those with college or above maternal education level, those with elementary school or below maternal education level were 49% more likely to consume Western fast food (odds ratio [OR] and 95% confidence interval [CI]: 1.49 [1.10-2.03]). Chinese fast food consumption rate increased by 12% with each year of increase in child's age (OR and 95% CI: 1.12 [1.02-1.23]). No significant associations between fast food consumption and health outcomes were detected. Adjusting for Western fast food consumption, children with lower maternal education were 71% and 43% more likely to have obesity and central obesity (ORs and 95% CIs: 1.71 [1.12-2.61] and 1.43 [1.00-2.03], respectively), and maternal body mass index was positively associated with child obesity, central obesity, and hypertension (ORs and 95% CIs: 1.11 [1.06-1.17], 1.12 [1.07-1.17], and 1.09 [1.03-1.15], respectively). Results were similar when Chinese fast food consumption was adjusted for.Conclusions: The prevalence of fast food consumption, obesity and hypertension is high among children in major cities in China. Maternal factors affect child outcomes. [ABSTRACT FROM AUTHOR]

Background: Congenital heart disease (CHD) is a common birth defect, and most cases occur sporadically. Mutations in key genes that are responsible for cardiac development could contribute to CHD. To date, the genetic causes of CHD remain largely unknown.Methods: In this study, twenty-nine candidate genes in CHD were sequenced in 106 patients with Tetralogy of Fallot (TOF) using target exome sequencing (TES). The co-immunoprecipitation (CO-IP) and luciferase reporter gene assays were performed in HEK293T cells, and wild-type and mutant mRNA of ZFPM2 were microinjected into zebrafish embryos.Results: Rare variants in key cardiac transcriptional factors and JAG1 were identified in the patients. Four patients carried multiple gene variants. The novel E1148K variant was located at the eighth Zinc-finger domain of FOG2 protein. The CO-IP assays in the HEK293T cells revealed that the variant significantly damaged the interaction between ZFPM2/FOG2 and GATA4. The luciferase reporter gene assays revealed that the E1148K mutant ZFPM2 protein displayed a significantly greater inhibition of the transcriptional activation of GATA4 than the wild-type protein. The wild-type mRNA and the E1148K mutant mRNA of ZFPM2 were injected into zebrafish embryos. At 48 hpf, in the mutant mRNA injection group, the number of embryos with an abnormal cardiac chamber structure and a loss of left-right asymmetry was increased. By 72 hpf, the defects in the chamber and left-right asymmetry became obvious.Conclusions: We performed TES in sporadic TOF patients and identified rare variants in candidate genes in CHD. We first validated the E1148 K variant in ZFPM2, which is likely involved in the pathogenesis of CHD via GATA4. Moreover, our results suggest that TES could be a useful tool for discovering sequence variants in CHD patients. [ABSTRACT FROM AUTHOR]

Background: Traditional linear regression analyses have detected increasing trends in the incidence of overweight/obesity among both genders in China. However, these previous regression analyses were limited in their ability to capture cross-distribution variations among effects. The objective of our study was to analyze the change in the body mass index (BMI) distribution of adults and investigated the relationships between the key covariates and the BMI distribution.Methods: We used longitudinal data from the China Health and Nutrition Surveys (CHNS) in 1991, 1993, 1997, 2000, 2004, 2006, 2009, and 2011, with at least two waves of data collection. In total, 17,819 participants aged 18-60 years (N = 8587 men and 9232 women) were included in the final analysis with 48,900 observations. The lambda-mu-sigma (LMS) method was used to describe changes in the BMI distribution. Separate sex-stratified longitudinal quantile regression (QR) analyses were used to investigate changes in the BMI distribution over time.Results: The main characteristics of the BMI changes in both genders were that the curves shifted to the right and the distributions became wider. All of the BMI percentile curves tended to increase from 1991 to 2011, where the levels increased more in the higher percentiles. The QR analyses showed that these patterns remain consistent after adjusting for individual and community level factors. Physical activity (PA) had a negative association with BMI for both genders in all percentiles. Income and energy intake were associated with positive changes in male BMI in the upper percentile. Sedentary time had a positive association with female BMI in the middle percentile. Compared with less educated women, women with senior school education at 75(th) percentile had 0.951 kg/m(2) lower BMIs.Conclusions: This longitudinal quantile regression suggests that effects of different covariates worked differently across the BMI distribution. Since social and economic characteristics in China have underlined the significant disparities in many aspects, national strategies to tackle overweight/obesity should be tailored as appropriate for various segments. [ABSTRACT FROM AUTHOR]

Background: Although a lower methylation level of whole genome has been demonstrated in Tetralogy of Fallot (TOF) patients, little is known regarding changes in specific gene DNA methylation profiles and the possible associations with TOF. In current study, the promoter methylation statuses of congenital heart defect (CHD) candidate genes were measured in order to further understand epigenetic mechanisms that may play a role in the development of TOF.Methods: The methylation levels of CHD candidate genes were measured using the Sequenom MassARRAY platform. QRT-PCR was used to analyze the mRNA levels of CHD candidate genes in the right ventricular myocardium of TOF cases and normal controls.Results: Methylation status analysis was performed on the promoter regions of 71 CHD candidate genes (113 amplicons). We found significant differences in methylation status, between TOF cases and controls, in 26 amplicons (26 genes) (p < 0.05). Of the 26 amplicons, 17 were up regulated and 9 were down regulated. Additionally, 14 of them were located in the CpG islands, 7 were located in the CpG island shores, and 5 were covering the regions near the transcription start site (TSS). The methylation status was subsequently confirmed and mRNA levels were measured for 7 represented candidate genes, including EGFR, EVC2, NFATC2, NR2F2, TBX5, CFC1B and GJA5. The methylation values of EGFR, EVC2, TBX5 and CFC1B were significantly correlated with their mRNA levels (p < 0.05).Conclusions: Aberrant promoter methylation statuses of CHD candidate genes presented in TOF cases may contribute to the TOF development and have potential prognostic and therapeutic significance for TOF disease. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to evaluate the prognostic value of TFPI-2 expression in breast cancer patients through examining the correlation between TFPI-2 expression and breast cancer clinicopathologic features.Methods: Immunohistochemical staining combined with digital image analysis was used to quantify the expression of TFPI-2 protein in breast tumor tissues. For evaluation of the prognostic value of TFPI-2 expression to each clinicopathologic factor, Kaplan-Meier method and COX's Proportional Hazard Model were employed.Results: TFPI-2 expression was significantly correlated with tumor size, lymph node metastasis, histologic grade, clinical stage, and vessel invasion. More importantly, TFPI-2 expression was also associated with disease-free survival (DFS) of breast cancer patients. We found that patients with high TFPI-2 expression had longer DFS compared with those with low or negative expression of TFPI-2 (P <0.05, log-rank test). Cox's regression analysis indicated that TFPI-2 expression, histologic grade, and vessel invasion might be significant prognostic factors for DFS, while TFPI-2 expression and histologic grade were the most significant independent predictors for tumor recurrence. Compared with the group with low/high TFPI-2 expression, the TFPI-2 negative group was more likely to have tumor relapse. The hazard ratio of DFS is 0.316 (P <0.01).Conclusions: Low or negative expression of TFPI-2 is associated with breast cancer progression, recurrence and poor survival outcome after breast cancer surgery. TFPI-2 expression in breast tumors is a potential prognostic tool for breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: miRNAs are a group of small RNA molecules regulating target genes by inducing mRNA degradation or translational repression. Aberrant expression of miRNAs correlates with various cancers. Although miR-135a has been implicated in several other cancers, its role in breast cancer is unknown. HOXA10 however, is associated with multiple cancer types and was recently shown to induce p53 expression in breast cancer cells and reduce their invasive ability. Because HOXA10 is a confirmed miR-135a target in more than one tissue, we examined miR-135a levels in relation to breast cancer phenotypes to determine if miR-135a plays role in this cancer type.Methods: Expression levels of miR-135a in tissues and cells were determined by poly (A)-RT PCR. The effect of miR-135a on proliferation was evaluated by CCK8 assay, cell migration and invasion were evaluated by transwell migration and invasion assays, and target protein expression was determined by western blotting. GFP and luciferase reporter plasmids were constructed to confirm the action of miR-135a on downstream target genes including HOXA10. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student"s t-test.Results: Here we report that miR-135a was highly expressed in metastatic breast tumors. We found that the expression of miR-135a was required for the migration and invasion of breast cancer cells, but not their proliferation. HOXA10, which encodes a transcription factor required for embryonic development and is a metastasis suppressor in breast cancer, was shown to be a direct target of miR-135a in breast cancer cells. Our analysis showed that miR-135a suppressed the expression of HOXA10 both at the mRNA and protein level, and its ability to promote cellular migration and invasion was partially reversed by overexpression of HOXA10.Conclusions: In summary, our results indicate that miR-135a is an onco-miRNA that can promote breast cancer cell migration and invasion. HOXA10 is a target gene for miR-135a in breast cancer cells and overexpression of HOXA10 can partially reverse the miR-135a invasive phenotype. [ABSTRACT FROM AUTHOR]

Background: China has seen rapid increase in obesity and hypertension prevalence and fast food consumption over the past decade. We examined status and risk factors for Western- and Chinese fast food consumption and their associations with health outcomes in Chinese children, and examined how maternal factors were associated with child health outcomes., Methods: Data of 1626 students aged 7-16 (11.6 ± 2.0) years and their parents in four mega-cities across China (Beijing, Shanghai, Nanjing, and Xi'an) were collected in the 2015 baseline survey of the Childhood Obesity Study in China Mega-cities. Weight, height, waist circumference, and blood pressure were measured. Food intake was assessed using questionnaire. Mixed models were used to examine the associations., Results: Among the children, 11.1% were obese, 19.7% were centrally obese, and 9.0% had hypertension. Obesity prevalence was much higher in boys than in girls (15.2% vs. 6.9% and 27.4% vs. 11.7%, respectively, both P < 0.001). About half (51.9% and 43.6%) of children consumed Western and Chinese fast food, respectively, over the past 3 months. Compared to those with college or above maternal education level, those with elementary school or below maternal education level were 49% more likely to consume Western fast food (odds ratio [OR] and 95% confidence interval [CI]: 1.49 [1.10-2.03]). Chinese fast food consumption rate increased by 12% with each year of increase in child's age (OR and 95% CI: 1.12 [1.02-1.23]). No significant associations between fast food consumption and health outcomes were detected. Adjusting for Western fast food consumption, children with lower maternal education were 71% and 43% more likely to have obesity and central obesity (ORs and 95% CIs: 1.71 [1.12-2.61] and 1.43 [1.00-2.03], respectively), and maternal body mass index was positively associated with child obesity, central obesity, and hypertension (ORs and 95% CIs: 1.11 [1.06-1.17], 1.12 [1.07-1.17], and 1.09 [1.03-1.15], respectively). Results were similar when Chinese fast food consumption was adjusted for., Conclusions: The prevalence of fast food consumption, obesity and hypertension is high among children in major cities in China. Maternal factors affect child outcomes.

Background: Dramatic increases in child overweight have occurred in China. A comprehensive look at trends in physical activity and sedentary behaviors among Chinese youth is needed. The study aimed to examine trends in domain-specific physical activity and sedentary behaviors, explore mean and distributional changes in predicted behaviors over time, and investigate how behaviors vary by residence., Methods: Using 2004-2011 China Health and Nutrition Survey data, adjusted means for MET-hours/week from physical activity and hours/week from sedentary behaviors were determined for school children (6-18 years), stratifying by gender, age group, and residence. Physical activity domains included in-school physical activity, active leisure (out-of-school physical activity), active travel (walking or biking), and domestic activity (cooking, cleaning, and child care). For each physical activity domain, the MET-hours/week measure was determined from the total weekly time spent (hours) in domain-specific activities and corresponding MET-values using the Compendium of Energy Expenditures for Youth. Sedentary behaviors included television, computer use, homework, and other behaviors (board games, toys, extracurricular reading and writing). For each sedentary behavior, the hours/week measure was determined from total weekly time spent in specific sedentary behaviors. Residence groups included megacities (population ≥ 20million), cities/towns (300,000 ≤ population < 20million), and rural/suburban areas (population < 300,000). Repeated measure linear mixed and quantile regression models were used to predict adjusted means., Results: Little change in physical activity behaviors occurred over time, with the exception of statistically significant trends toward increased domestic activity among male children (p < .05). Across all gender and age groups, statistically significant trends over time toward an average increase in computer use were seen (p < .01); these increases were largely driven by those ≥50th percentile on the distribution. Children living in megacities (versus rural areas) reported higher levels of physical activity, homework, and computer use., Conclusions: Intensified, systematic intervention and policy efforts promoting physical activity and reducing sedentary behaviors among children are needed.

Background: Alström syndrome is a rare multi-systemic disorder with a broad spectrum of symptoms. This syndrome is characterized by childhood retinal degeneration; sensorineural hearing loss; obesity; type 2 diabetes mellitus; cardiomyopathy; systemic fibrosis; and pulmonary, hepatic, and renal failure., Case Presentation: A Chinese quartet family with two siblings predominantly affected by cone-rod dystrophy and short stature were recruited. The craniofacial dysmorphism and on-set age-of-cone-rod dystrophy in the proband showed a minor intrafamilial variability. Whole genome sequencing was performed to provide the full spectrum of the two siblings' genetic variations. In this study, we present the patients' clinical features and our interpretation of the whole genome sequencing data. After examining the data, we focus on two compound heterozygous mutations, (c.3902C > A, p.S1301X; c.6436C > T, p.R2146X) in ALMS1, which are shared by two siblings., Conclusion: We reported a novel ALMS1 mutation. Whole genome sequencing is a powerful tool to provide the full spectrum of genetic variations for heterogeneous disorders such as Alström syndrome.

Background: Congenital heart disease (CHD) is a common birth defect, and most cases occur sporadically. Mutations in key genes that are responsible for cardiac development could contribute to CHD. To date, the genetic causes of CHD remain largely unknown., Methods: In this study, twenty-nine candidate genes in CHD were sequenced in 106 patients with Tetralogy of Fallot (TOF) using target exome sequencing (TES). The co-immunoprecipitation (CO-IP) and luciferase reporter gene assays were performed in HEK293T cells, and wild-type and mutant mRNA of ZFPM2 were microinjected into zebrafish embryos., Results: Rare variants in key cardiac transcriptional factors and JAG1 were identified in the patients. Four patients carried multiple gene variants. The novel E1148K variant was located at the eighth Zinc-finger domain of FOG2 protein. The CO-IP assays in the HEK293T cells revealed that the variant significantly damaged the interaction between ZFPM2/FOG2 and GATA4. The luciferase reporter gene assays revealed that the E1148K mutant ZFPM2 protein displayed a significantly greater inhibition of the transcriptional activation of GATA4 than the wild-type protein. The wild-type mRNA and the E1148K mutant mRNA of ZFPM2 were injected into zebrafish embryos. At 48 hpf, in the mutant mRNA injection group, the number of embryos with an abnormal cardiac chamber structure and a loss of left-right asymmetry was increased. By 72 hpf, the defects in the chamber and left-right asymmetry became obvious., Conclusions: We performed TES in sporadic TOF patients and identified rare variants in candidate genes in CHD. We first validated the E1148 K variant in ZFPM2, which is likely involved in the pathogenesis of CHD via GATA4. Moreover, our results suggest that TES could be a useful tool for discovering sequence variants in CHD patients.

Background: Diffuse large B-cell lymphoma (DLBCL) of leukemic phase is a rare clinical manifestation, but is highly prevalent with central nervous system involvement (CNSI). Little is known about this rare clinical observation., Methods: We reviewed the clinical characteristics of 40 DLBCL patients with leukemic phase identified by flow cytometry and analyzed BCL2 and MYC aberrations by fluorescence in situ hybridization., Results: The median age of these 40 patients was 46 years (range, 15-75) with 19 men patients. All patients had bone marrow involvement, and fourteen (35.0%) had CNSI. There were respectively 14 patients (35.0%) had the BCL2 or MYC gain/amplification and nine of them (22.5%) simultaneously had both aberrations. Compared to those without CNSI, CNSI was found more commonly in male patients (71.4 vs. 34.6%, p = 0.046), in those with IPI scores of 4-5 (57.1% vs. 11.5%, p = 0.001), and in those with elevated serum LDH (100 vs. 61.5%, p = 0.007) and both MYC and BCL2 rearrangement (88.9 vs. 19.4%; p = 0.000). BCL2 and MYC rearrangements were the sole independent factor correlated with CNSI., Conclusion: It is possible that both BCL2 and MYC gene aberrations may contribute to the high incidence of CNSI observed in leukemic phase of patients with DLBCL.

Background: Linear nevus sebaceous syndrome (LNSS) is a multisystem disorder that includes nevus sebaceous and central nervous system, ocular and skeletal anomalies. We report the first case of a KRAS G12D mosaic mutation in a patient diagnosed with LNSS., Case Presentation: A 3-month-old female with a clinical diagnosis of LNSS presented with intermittent epilepsy. Her mother carefully collected a skin lesion sample from scratched-off scurf obtained from the patient's nails. DNA was extracted, and long-range PCR was performed to amplify the KRAS gene, which was then analyzed by next-generation sequencing. The results revealed the presence of a low-level heterozygous mutation in the KRAS gene (c.35C>T; p.G12D, 5 %)., Conclusions: These findings suggest that the KRAS somatic mosaic mutation in this patient may have caused her skin and eye lesions and epilepsy. With this correct diagnosis, the infant can be effectively treated.

Background: NKX2-5, GATA4 and HAND1 are essential for heart development, however, little is known regarding their epigenetic regulation in the pathogenesis of tetralogy of fallot (TOF)., Methods: Methylation levels were measured in three regions of NKX2-5 (M1: -1596 bp ~ -1374 bp, M2: -159 bp ~ 217 bp and M3: 1058 bp ~ 1524 bp), one region of GATA4 (M: -392 bp ~ 107 bp) and three regions of HAND1 (M1: -887 bp ~ -414 bp, M2: -436 bp ~ 2 bp and M3: 37 bp ~ 398 bp) using the Sequenom MassARRAY platform. QRT-PCR was used to analyze NKX2-5 and HAND1 mRNA levels in the right ventricular myocardium of TOF patients., Results: TOF patients had a significantly higher NKX2-5&#95;M3 median methylation level than controls (41.65% vs. 22.18%; p = 0.0074; interquartile range [IQR]: 30.46%-53.35%, N = 30 and 20.07%-24.31%, N = 5; respectively). The HAND1&#95;M1 median methylation level was also significantly higher in TOF patients than controls (30.05% vs. 17.54%; p = 0.0054; IQR: 20.77%-40.89%, N = 30 and IQR: 14.69%-20.64%; N = 6; respectively). The methylation statuses of NKX2-5&#95;M1, NKX2-5&#95;M2, GATA4&#95;M, HAND1&#95;M2 or HAND1&#95;M3 were not significantly different in TOF patients compared to controls. The methylation values for NKX2-5&#95;M3 were negatively correlated with mRNA levels (r = - 0.463, p = 0.010, N = 30) and there was a significant association between HAND1&#95;M1 methylation status and mRNA levels (r = - 0.524, p = 0.003, N = 30) in TOF patients., Conclusions: Aberrant methylation statuses of the NKX2-5 gene body and HAND1 promoter regions are associated with the regulation of gene transcription in TOF patients and may play an important role in the pathogenesis of TOF.