BackgroundUnderlying causes in Chinese children with recurrent acute liver failure (RALF), including liver crises less than full acute liver failure, are incompletely understood. We sought to address this by searching for genes mutated in such children.MethodsFive unrelated Chinese boys presenting between 2012 and 2015 with RALF of unexplained etiology were studied. Results of whole exome sequencing were screened for mutations in candidate genes. Mutations were verified in patients and their family members by Sanger sequencing. All 5 boys underwent liver biopsy.Results NBAS was the only candidate gene mutated in more than one patient (biallelic mutations, 3 of 5 patients; 5 separate mutations). All NBAS mutations were novel and predictedly pathogenic (frameshift insertion mutation c.6611_6612insCA, missense mutations c.2407G > A and c.3596G > A, nonsense mutation c.586C > T, and splicing-site mutation c.5389 + 1G > T). Of these mutations, 3 lay in distal (C-terminal) regions of NBAS, a novel distribution.Unlike the 2 patients without NBAS mutations, the 3 patients with confirmed NBAS mutations all suffered from a febrile illness before each episode of liver crisis (fever-related RALF), with markedly elevated alanine aminotransferase and aspartate aminotransferase activities 24-72 h after elevation of body temperature, succeeded by severe coagulopathy and mild to moderate jaundice.ConclusionsAs in other countries, so too in China; NBAS disease is a major cause of fever-related RALF in children. The mutation spectrum of NBAS in Chinese children seems different from that described in other populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-017-0636-3) contains supplementary material, which is available to authorized users.

Background: Skin barrier functions develop after birth and may be related to skin disorders in infants. We aimed to assess associations between dynamic trends of four skin barrier functional parameters in early life with infant atopic dermatitis (AD). Methods:Based on the prospective cohort MKNFOAD (NCT02889081), we examined transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin pH, and sebum content at five anatomical sites (cheek, forehead, forearm, abdomen, and lower leg) in 418 term infants at birth, 42 days, and 6 months. Trend differences by sex and association with AD at age 1 year were tested using variance analyses. Associations of the parameters with AD risk were tested using discrete time survival analysis, adjusting extensive covariates including parental history of allergy, infant's sex, birth weight (kg), and delivery mode. Odds ratios (ORs) and 95% confidence interval (CIs) were reported.Results: Overall TEWL and SCH appeared trends of increase while skin surface pH and sebum content showed trends of decrease within the first six postnatal months. Sex differences were significant for sebum content only (p < 0.001). After adjustment for parental and children covariates, cheek TEWL at birth (OR = 1.26, 95% CI 1.00-1.57, p = 0.045) and 42 days (OR = 1.52, 95% CI 1.17-1.97, p = 0.002) were significantly associated with increased AD risk. Associations were not observed between SCH, skin pH, and sebum content at birth or 42 days with AD.Conclusions: Skin barrier functions of Chinese term infants varied nonlinearly after birth. Higher postnatal TEWL levels in early life indicate higher risk of early-onset AD.

Background: Maternal vitamin D status during pregnancy has been linked with the risk of atopic dermatitis (AD) in children, while the results were inconsistent. The objective of this study was to assess the potential association. Methods: Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in pregnant women from the birth cohort MKFOAD. Infant AD was diagnosed according to Williams' criteria. Multivariate logistic regression model was used to examine the association of maternal serum 25(OH)D levels in the first, second, and third trimester of gestation with the risk of infant AD at first year of age. Results: In total, 121 (26.5%) of 456 infants developed AD prior to 1 year of age. In general, higher maternal serum 25(OH)D levels throughout pregnancy were associated with increased risks of AD in infants prior to 1 year of age in multivariate logistic regression models, with borderline statistical significance in the first (per ln unit increase: adjusted OR = 1.93, 95% CI: 0.96, 3.88) and second (per ln unit increase: adjusted OR = 1.72, 95% CI: 0.93, 3.19) trimester. Multivariate logistic regression models using categorical variables of maternal 25(OH)D levels by tertiles showed similar results: Infants born to mothers with serum 25(OH)D levels in the highest tertile had higher risk of AD than those with 25(OH)D in the lowest tertile. Conclusions:The present study found some evidence supporting that higher maternal 25(OH)D levels during pregnancy increased the risk of infant AD. However, the clinical implication of the findings should be limited for those with blood levels over the recommendations.

Background: Maternal folate status is linked with the risk of allergic disorders including atopic dermatitis (AD) in children, but findings remain inconclusive. We aim to assess the relationship between maternal folate status in early gestation and earlyonset infant AD, based on a prospective mother-child cohort study. Methods: Pregnant women were recruited at 12-14 weeks of gestation. Red blood cell folate (RBC folate) and serum folate concentrations were examined at enrollment. Periconceptional folic acid supplementation was investigated through a self-administered questionnaire. The primary outcome was AD incidence before 6 months of age, diagnosed according to Williams' criteria. Multivariate logistic regression was used to evaluate associations of maternal folate status with infant AD by adjusting parental and child covariates. Results: In total, 107 (23.4%) of 458 infants developed AD before 6 months, with more male infants affected (P = .002). Higher maternal RBC folate levels (per 100 ng/ mL) were associated with an increased risk of AD (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.04-1.31). An RBC folate level ≥620 ng/mL was associated with increased infant AD by 91% (aOR 1.91, 95% CI 1.09-3.36). However, associations were not observed for maternal serum folate at early gestation or periconceptional folic acid supplement intakes. Conclusions: We provide the first evidence that higher maternal RBC folate concentrations during early gestation are associated with increased early-onset infant AD. Our findings support the importance of maintaining appropriate folate levels during the periconceptional period to reduce the risk of AD in infants.

Abstract. Intracranial dural arteriovenous fistulas (DAVFs) are complex intracranial vascular malformations that may lead to hemorrhage. Although the precise mechanisms by which DAVFs occur remain unknown, dural angiogenesis may be a vital factor in its pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) significantly influences angiogenesis; however, the association between DAVF and Nrf2 remains unclear. Therefore, the present study investigated whether DAVF alters the expression of Nrf2 in an experimental animal model of DAVF. The DAVF group underwent surgery of the left common carotid artery-external jugular vein anastomosis, cauterization of the vein draining transverse sinus and thrombosis of the sagittal sinus to induce venous hypertension (VH). At 1, 4 and 7 days post surgery, rats were sacrificed to collect brain samples. Western blot analysis, immunofluorescence staining and reverse transcription-quantitative polymerase chain reaction were used to determine whether DAVF activated the Nrf2 signaling pathway. The results demonstrated that the expression of Nrf2 mRNA and protein, and the expression of its downstream genes heme oxygenase-1 and NAD(P)H: quinine oxidoreductase-1 significantly increased 1 day after surgery. The expression of these genes decreased but remained high 4 days following surgery and only returned to baseline 7 days after surgery. Compared with the sham-surgery and control groups, DAVF-induced brain edema reached a peak 1 day following DAVF surgery and only returned to normal levels 7 days post-surgery. Taken together, these data indicate the potential contribution of Nrf2 to the formation of DAVFs and suggest that VH may induce the upregulation of Nrf2.