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Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese [Control] from cardiac centers in China) and analyzed by genome-wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein-protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel "TOF-specific CNVs" were identified with prevalence of CNVs of 21.5% in chromosomes 1-20 and 37.0% including Chr21/22. In chromosomes 1-20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF-specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF.

An anomalous origin of the left coronary artery (LCA) is a relatively uncommon congenital heart defect that can lead to myocardial ischemia and sudden cardiac death. An LCA arising from the pulmonary artery and an LCA arising from the opposite sinus of Valsalva are the common types of anomalous origins of the LCA. Echocardiographic assessment of the coronary arteries is an important component of the routine cardiovascular evaluation, but echocardiographic "pseudo images" of LCA origination can be present in some patients. Detection of an anomalous origin of the LCA remains a challenge to sonographers.

Silica nanoparticles (NPs) have been widely used in food products as an additive; however, their toxicity and safety to the human body and the environment still remain unclear. As a food additive, silica NPs firstly enter the human gastrointestinal tract along with food, thus their gastrointestinal toxicity deserves thorough study. Herein, we evaluated the toxicity of food additive silica NPs to cells originating from the gastrointestinal tract. Four silica NP samples were introduced to human gastric epithelial cell GES-1 and colorectal adenocarcinoma cell Caco-2 to investigate the effect of silica sample, exposure dose and exposure period on the morphology, viability and membrane integrity of cells. The cell uptake, cellular reactive oxygen species (ROS) level, cell cycle and apoptosis were determined to reveal the toxicity mechanism. The results indicate that all four silica NPs are safe for both GES-1 and Caco-2 cells after 24-h exposure at a concentration lower than 100 µg ml–1. At a higher concentration and longer exposure period, silica NPs do not induce the apoptosis/necrosis of cells, but arrest cell cycle and inhibit the cell growth. Notably, silica NPs do not pass through the Caco-2 cell monolayer after 4-h contact, indicating the low potential of silica NPs to cross the gastrointestinal tract in vivo. Our findings indicate that silica NPs could be used as a safe food additive, but more investigations, such as long-term in vivo exposure, are necessary in future studies. Copyright © 2013 John Wiley & Sons, Ltd.

Objectives/Hypothesis: To investigate the prevalence of allergic rhinitis (AR) and its associated risk factors in preschool children in Beijing. Study design: Two-stage, clustered, stratified random sample study. Methods: Parents of 4,075 children aged 3, 4, and 5 years in urban and suburban areas were surveyed using a questionnaire. A random subgroup of 1,067 children was examined by otolaryngologists with skin prick test (SPT). Results: The survey response rate was 98.3%. Based on the criteria published by ARIA document, the prevalence of epidemiologic AR was 48% (53.2% in urban areas; 43.4% in suburban areas). Among 795 children with epidemiologic AR, sensitization to common inhalant allergens was confirmed by a positive SPT in 248 children (31.2%). Thus, the adjusted prevalence of clinical AR was 14.9% (19.5% in urban areas; 10.8% in suburban areas). In these AR children, 166 (67.1%) were intermittent and 82 (32.9%) persistent, with moderate/severe symptoms in 103 (41.5%). The most common inhalant allergens were Alternaria tenuis (55.7%), followed by Dermatophagoides farina (39.4%), and Dermatophagoides pteronyssinus (38.6%). Both asthma (adjusted OR 4.88, 95% CI: 3.48–6.86) and eczema (adjusted OR: 1.49, 95% CI: 1.15–1.94) appear to be significant concomitant risk factors for AR. Conclusions: The prevalence of AR in young children can be overestimated using epidemiologic criteria. AR is a common disease in Asian preschool children, with an increasing trend as children get older, and is higher in urban than suburban areas—suggesting an important role for environmental risk factors in AR. Laryngoscope, 2013