Meng Mao

Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) with a multitude of clinical manifestations. Some CF patients develop clinically significant anemia, suggesting that CFTR may regulate hematopoiesis. Here, we report that cftr mutant zebrafish model exhibits primitive and definitive hematopoietic defects with impaired Wnt signaling. Cftr is found to interact, via its PDZ-binding domain (PDZBD), with Dishevelled (Dvl), a key component of Wnt signaling required for hematopoietic progenitor specification, thus protecting Dvl from Dapper1 (Dpr1)-induced lysosomal degradation. Defective hematopoiesis and impaired Wnt signaling in cftr mutant can be rescued by overexpression of wild-type or channel function-defective G551D mutant CFTR with an intact PDZBD, but not Cftr with mutations in the PDZBD. Analysis of human database (http://r2.amc.nl) shows that CFTR is positively correlated with DVL2 and Wnt-related hematopoietic factors in human blood system. The results reveal a previously unrecognized role of CFTR, which is independent of its channel function, in regulating DVL degradation and thus Wnt signaling required for hematopoiesis in both zebrafish and humans, providing an explanation for the anemic phenotype of CF patients.

Infant feeding regimens, including breastfeeding, formula-feeding, or a combination of the two, may influence infant health-related quality of life (HRQOL). However, few studies have examined this association. This prospective cohort study assessed HRQOL in relation to three parent-selected feeding regimens: exclusively breastfed (n = 136), exclusively study formula-fed (n = 140), and mixed-fed with study formula and breast milk (n = 151). Healthy Chinese infants were enrolled at their first normally scheduled well infant clinic visit at age 42 days (study day 1). Parents independently chose their infants’ feeding regimens prior to recruitment into the study, with infants in the formula and mixed-fed groups already consuming an infant formula enriched with α-lactalbumin and increased sn-2 palmitate and oligofructose. The Infant and Toddler Quality of Life Questionnaire, which includes six infant-focused and three parent-focused concepts, was used to assess HRQOL at day 1 and at a follow-up visit 48 days later. Scores for each concept ranged from 0 to 100. Parent quality of life (assessed using the Mental Component Summary score of the SF-12v2 Health Survey) was included in the ANCOVA model to adjust for its potential effect on parent’s perception of infant HRQOL. HRQOL concept scores were high in all three study groups at both visits (mean scores 71–95). Day 1 HRQOL scores were not significantly different between groups. At day 48, 5 of 9 HRQOL scores were not significantly different between groups. However, scores for Temperament and Moods, General Health Perceptions and Parent Impact–Time were slightly but statistically significantly lower in the formula-fed group (mean scores 75–86; all p ≤ 0.01) compared to the breastfed (78–90) and mixed-fed (77–91) groups. Day 48 Parent Impact–Emotional scores were also significantly lower by a small margin (4 points; p = 0.003) in the formula-fed group compared with the breastfed group. HRQOL was high in this population of healthy infants, with only a few small differences in HRQOL concept scores observed between breastfed, formula-fed and mixed-fed infants. These results indicate favorable physical, mental, and social well-being in these infants and parents. Assessment of infant HRQOL is therefore feasible and provides valuable insight into parental perceptions of their child’s health and well-being. ClinicalTrials.gov, NCT01370967 .

Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children

Congenital heart defect is one of the most common birth defects. The isolated ventricular septal defect (VSD) has higher morbidity, and spontaneous closure may occur. Previously many studies about the prognosis of ventricular septal defect in childhood were conducted; in contrast, few studies on evolution and prognosis of ventricular septal defect from fetus to postnatal life have been available. This research aimed to determine the evolution of isolated ventricular septal defect during the period of fetus and postnatal life, and analyze the association between the diameter or location of VSD and the spontaneous closure of VSD. All pregnant women seen at the prenatal diagnosis center of the West China Second Hospital were recruited. From June 2011 to June 2014, these participants underwent the fetal 2-dimensional and color Doppler echocardiographic examinations, and the fetuses with isolated VSD were included in the study, and those with other malformations or abnormal chromosome were excluded. This study was a prospective and longitudinal research. These fetuses were followed-up until the VSD closed spontaneously, or were surgically repaired or percutaneously closed. Outcomes of all the cases were recorded. There were 234 fetuses with isolated VSD who were recruited in our research cohort. Twelve of 234 lost to follow-up, 5 of 234 were still in uterus. Totally 217 fetuses were followed up. One hundred eighty-nine of 217 (87.1%) cases were delivered. The pregnancies were terminated in 28 of 217 (12.9%) cases. Ten cases died after birth. Of the 179 delivered cases, the rate of VSD spontaneous closure was 45.2% (81/179), the VSD of 49 cases (27.4%, 49/179) spontaneously closed in uterus. The VSD of 17.9% (32/179) cases spontaneously closed after birth and those of 75% (24/32) cases closed in the first year of life. Furthermore, these participants were divided into 3 groups according to the diameter of VSD in fetus. There were 87 cases in ≤ 2.0 mm group, 51 spontaneously closed (59%, 51/87) and 30 of 84 spontaneously closed (36%, 30/84) in 2.1-5.0 mm group. There were no spontaneous closure in > 5.0 mm group. There was a significant difference in spontaneous closure rate between the 3 groups (χ(2) = 15.200, P = 0.001). Nevertheless, these participants were divided into 2 groups according to the location of VSD in fetus (perimembrane VSD (P-VSD) group and muscular VSD (M-VSD) group). There were 152 cases in P-VSD group, 69 spontaneously closed (45.4%, 69/152) and 12 of 27 spontaneously closed (44%, 12/27) in M-VSD group. There was no significant difference in spontaneous closure between P-VSD and M-VSD (χ(2) = 0.008, P = 0.950). There was a high spontaneous closure rate of VSD in the period of late pregnancy. The most of postnatal VSD were spontaneously closed within one year of age. The spontaneous closure rates of fetal VSD with different diameter were different. The spontaneous closure rate of VSD with smaller diameter was higher.

We evaluated the relationship between total serum immunoglobulin E (IgE) levels and pregnancy outcome in a prospective cohort study focusing on fetal growth restriction (FGR). Sixty women with FGR and twenty with normal singleton pregnancy were enrolled during their third trimester. Infants were followed up for 6 months. Blood samples were obtained from pregnant women during the third trimester; cord blood samples were also taken. Six months after birth, blood samples were obtained from infants. Demographic and baseline characteristics were compared between groups. Birth weight, length and head circumference of neonates in the FGR group were lower than those in the control group. Total serum IgE level was significantly increased in third-trimester pregnant women with FGR compared with normal group (P < 0.05). However, this trend was not observed in the cord blood at birth or peripheral blood of 6-month-old infants. The prevalence of atopic eczema between the 2 groups was similar. Linear regression analysis revealed that the IgE level in the third trimester was negatively correlated with birth weight (P < 0.05). Higher serum IgE level in the cord blood was significantly associated with an increased risk of being small for gestational age (P < 0.05). In conclusion, IgE levels in the third trimester of pregnancy and cord blood are strongly related to birth outcomes of FGR.

The effective treatment for cerebral ischemia has not yet been established. Hepatocyte growth factor (HGF) is a potent pleiotropic cytokine that is involved in cell and tissue regeneration, including in the central nervous system. Studies have demonstrated that an exogenous administration of HGF protects brain tissue from ischemic damage. In response to binding to the receptor c‑Met, HGF activates the downstream signaling pathways (including the phosphatidylinositol 3-kinase/Akt, Ras/MAPK and signal transducer and activator of transcription pathways) which leads to various cellular responses involved in angiogenesis, glial scar formation, anti‑apoptosis and neurogenesis. The purpose of this review is to summarize the present understanding of the therapeutic potential of HGF in cerebral ischemia.

Maternal obesity caused by overnutrition during pregnancy increases susceptibility to metabolic risks in adulthood, such as obesity, insulin resistance, and type 2 diabetes; however, whether and how it affects the cognitive system associated with the brain remains elusive. Here, we report that pregnant obesity induced by exposure to excessive high fatty or highly palatable food specifically impaired reversal learning, a kind of adaptive behavior, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defects possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. These collective data add a novel perspective of understanding the adverse postnatal sequelae in central nervous system induced by developmental programming and the related molecular mechanism through which priming of risk for developmental disorders may occur during early life.

The neonates, particularly small-for-gestational-age (SGA) ones, are susceptible to various microbial infections. Natural killer (NK) cells are critical components of host innate immunity system and the main source of the inflammatory cytokines, which provide critical protection during the early phase of viral infections before the development of an appropriate adaptive immune response. However, little is known about the antiviral effects of NK cells in neonates especially the SGA population. Herein, a prospective descriptive study was performed to determine the differences of NK cell immunity among adults, appropriate-for gestational-age (AGA) and SGA neonates. Adults have much higher NK cell number in peripheral blood than that in cord blood from neonates. In response to influenza virus stimulation, neonatal NK cells, especially SGA baby cells, expressed significantly lower antiviral cytokines including perforin, interferon (IFN)-γ and tumor-necrosis factor (TNF)-α responses than adult NK cells. In addition, the antiviral cytokine responses of NK cells were positively correlated with neonatal birth weight. Our data suggested that the depressed antiviral activity and less frequency of NK cells are likely to be responsible for the high susceptibility to microbial infection in neonates, at least in part. Improving the function of innate immunity may provide a new way to defend virus infection.