The RNA-binding protein QKI belongs to the hnRNP K-homology domain protein family, a well-known regulator of pre-mRNA alternative splicing and is associated with several neurodevelopmental disorders.Qkiis found highly expressed in developing and adult hearts. By employing the human embryonic stem cell (hESC) to cardiomyocyte differentiation system and generating QKI-deficient hESCs (hESCs-QKI^del) using CRISPR/Cas9 gene editing technology, we analyze the physiological role of QKI in cardiomyocyte differentiation, maturation, and contractile function. hESCs-QKI^dellargely maintain normal pluripotency and normal differentiation potential for the generation of early cardiogenic progenitors, but they fail to transition into functional cardiomyocytes. In this work, by using a series of transcriptomic, cell and biochemical analyses, and the Qki-deficient mouse model, we demonstrate that QKI is indispensable to cardiac sarcomerogenesis and cardiac function through its regulation of alternative splicing in genes involved in Z-disc formation and contractile physiology, suggesting thatQKIis associated with the pathogenesis of certain forms of cardiomyopathies.

Background: To investigate epidemiologic features of Kawasaki disease (KD) in Shanghai from 2013 through 2017 and identify risk factors for coronary artery lesions (CAL).Methods: As in our previous three surveys, a set of questionnaires and diagnostic guidelines for KD were sent to 50 hospitals providing pediatric medical care in Shanghai. Medical records of KD patients diagnosed from January 2013 through December 2017 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify risk factors for CAL.Results: A total of 4452 cases were enrolled. Male-to-female ratio was 1.7:1. The incidence of KD was 68.8 to 107.3 per 100,000 children aged 10 days, were independently associated with CAL.Conclusions: The incidence of KD in Shanghai had substantially increased while the proportion of CAL had substantially decreased as compared with our previous surveys. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were risk factors for CAL.

OBJECTIVE To investigate the association of folate and vitamin B₁₂ in early pregnancy with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS The data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B₁₂ measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks’ gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association. RESULTS A total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B₁₂ were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19–2.53) (P = 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ≥600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03–2.41) (P = 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (P_trend = 0.021). Vitamin B₁₂ was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P = 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B₁₂ with GDM was observed. CONCLUSIONS Higher maternal RBC folate and vitamin B₁₂ levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B₁₂ is not significantly associated with GDM.