The transcription factor GATA4 is essential for heart morphogenesis. Heterozygous mutation of GATA4 causes familial septal defects. However, the phenotypic spectrum of heterozygous GATA4 mutation is not known. In this study, we defined the cardiac phenotypes that result from heterozygous mutation of murine Gata4. We then asked if GATA4 mutation occurs in humans with these forms of congenital heart disease (CHD). In mice, heterozygous Gata4 mutation was associated with atrial and ventricular septal defect (ASD, VSD), endocardial cushion defect (ECD), RV hypoplasia, and cardiomyopathy. Genetic background strongly influenced the expression of ECD and cardiomyopathy, indicating the presence of important genetic modifiers. In humans, nonsynonymous GATA4 sequence variants were associated with ECD (2/43), ASD (1/8), and RV hypoplasia in the context of double inlet left ventricle (1/9), forms of CHD that overlapped with abnormalities seen in the mouse model. These variants were not found in at least 500 control chromosomes, and encode proteins with non-conservative amino acid substitutions at phylogenetically conserved positions, suggesting that they are disease-causing mutations. Cardiomyopathy was not associated with GATA4 mutation in humans. These data establish the phenotypic spectrum of heterozygous Gata4 mutation in mice, and suggest that heterozygous GATA4 mutation leads to partially overlapping phenotypes in humans. Additional studies will be

In previously untreated, advanced NSCLC patients, treatment with TC plus endostar seemed to improve ORR. However, the differences in PFS or OS between the two groups were not statistically significant. Treatment with TC plus endostar exhibited a good safety profile.

Neoadjuvant erlotinib was well tolerated and may improve the radical resection rate in this patient population. Next-generation sequencing may predict outcomes with preoperative TKIs.

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Objective Gallstone disease (GSD) is related to multiple cardiovascular risk factors; the present study was to prospectively examine the association between GSD and ischemic heart disease (IHD). Approach and Results We examined the association of GSD with IHD among 199,292 men and 288,081 women aged 30–79 years in the China Kadoorie Biobank study. Participants with cancer, heart disease, and stroke at baseline were excluded. Cox proportional hazards regression model was used to estimate the association of GSD with IHD. The prevalence of self-reported GSD was 3.7% in men and 7.3% in women at baseline. During 3,431,124 person-years of follow-up between 2004 and 2013 (median, 7.2 years), we documented 10,245 incident IHD cases in men and 14,714 in women. As compared with men without GSD at baseline, the multivariate-adjusted hazard ratio for IHD was 1.11 (95% confidence interval [CI], 1.02–1.22) for men with GSD; the respective hazard ratio was 1.27 (95% CI, 1.20–1.34) in women and 1.23 (95% CI, 1.17–1.28) in the whole cohort. The sex difference in IHD risk associated with GSD was statistically significant (P=0.009 for interaction with sex). In addition, we found the association between GSD and IHD was stronger in non-hypertensive than hypertensive women (P<0.001 for interaction). Conclusions In this large prospective study, the presence of GSD was associated with an increased risk of incident IHD, independent of other risk factors of cardiovascular disease. Our findings suggest novel prevention strategy to mitigate heart disease through improvement of gastrointestinal health.