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Influence of prevention of caffeine citrate on cytokine profile and bronchopulmonary dysplasia in preterm infants with apnea.
Kou, C, Han, D, Li, Z, Wu, W, Liu, Z, Zhang, Y, Gao, Z
Minerva pediatrica. 2020;(2):95-100
Abstract
BACKGROUND This study aims to investigate the preventive effects of caffeine citrate on cytokine profile and bronchopulmonary dysplasia (BPD) in preterm infants with apnea. METHODS Preterm infants with apnea who were born at less than 32 weeks of gestational age and birth weight ≤1500 g were randomly divided into caffeine citrate prevention group and caffeine citrate treatment group. Preterm infants in caffeine citrate prevention group who were at risk of developing recurrent apnea were given to caffeine citrate within 8 h after birth. Those in caffeine citrate treatment group experienced apnea after birth were given to caffeine citrate for treatment. Preterm infants in both groups were treated with the same respiratory management and other conventional therapy. After drug discontinuation, levels of cytokine profile, and incidence of BPD were compared between two groups. RESULTS A total of 56 preterm infants were enrolled. Differences in gestational age (P=0.11) and birth weight (P=0.251) were not statistically significant. Differences in application time of caffeine citrate (P=0.356), hour of ventilator use (P=0.152), length of stay (P=0.416) and BPD morbidity (P=1.00) between two groups were not statistically significant. At birth, there were no statistically significant in levels of IL-6 (P=0.063) and IL-8 (P=0.125) between two groups. After conventional therapy, levels of IL-6 (P=0.001) and IL-8 (P=0.001) significantly decreased in caffeine citrate prevention group compared with those in caffeine citrate treatment group. CONCLUSIONS Prevention usage of caffeine citrate in preterm infants with apnea could reduce the level of cytokine profile and the incidence of BPD.
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Genetic Association Analyses Highlight IL6, ALPL, and NAV1 As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis.
Thériault, S, Dina, C, Messika-Zeitoun, D, Le Scouarnec, S, Capoulade, R, Gaudreault, N, Rigade, S, Li, Z, Simonet, F, Lamontagne, M, et al
Circulation. Genomic and precision medicine. 2019;(10):e002617
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Abstract
BACKGROUND Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes, LPA and PALMD, have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS. METHODS A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits. RESULTS In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci: IL6 (interleukin 6) on 7p15.3 and ALPL (alkaline phosphatase) on 1p36.12. A TWAS integrating gene expression from 233 human aortic valves identified NAV1 (neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of NAV1 in valve tissues. Fine-mapping identified rs1800795 as the most likely causal variant in the IL6 locus. The signal identified colocalizes with the expression of the IL6 RNA antisense in various tissues. Phenome-wide association analyses in the UK Biobank showed colocalized associations between the risk allele at the IL6 lead variant and higher eosinophil count, pulse pressure, systolic blood pressure, and carotid artery procedures, implicating modulation of the IL6 pathways. The risk allele at the NAV1 lead variant colocalized with higher pulse pressure and higher prevalence of carotid artery stenosis. Association results at the genome-wide scale indicated genetic correlation between CAVS, coronary artery disease, and cardiovascular risk factors. CONCLUSIONS Our study implicates 3 new genetic loci in CAVS pathogenesis, which constitute novel targets for the development of therapeutic agents.