Integrative analysis of microRNA and mRNA expression profiles in fetal rat model with anorectal malformation

Background Anorectal malformations (ARMs) are the most common congenital malformation of the gut, and regulated by multiple signal transduction pathways. The microRNA (miRNA) expression profiles and their biologial functions in anorectal malformations (ARMs) remain unclear. The aim of our study was to evaluate miRNA and mRNA expression profiles in the ARM rats. Methods and Materials ARM was induced with ethylenethiourea (ETU) on gestational day 10. Cesarean deliveries were performed to harvest the embryos on gestional day 20. For the extraction of total RNA, 1 cm terminal hindgut samples were obtained from three fetal rats that had similar weights. The microarrays and quantitative RT-PCR analysis were conducted to evaluate the miRNA and mRNA expression profiles in normal fetal rats (n = 3) and ARM fetal rats (n = 3). Results In total, 33 miRNAs and 772 mRNAs were significantly and differentially expressed in terminal hindgut tissues of ARM group versus control group. Functional annotation was performed to understand the functions and pathways of differentially expressed mRNAs. Also, we constructed a miRNA-target gene regulatory network including 25 differentially expressed miRNAs and 76 mRNAs. Furthermore, the credibility of the microarray-based results were validated by using qRT-PCR. Conclusion The miRNA and mRNA expression in terminal hindgut tissue of ARM fetal rats might provide a basis for further research on the pathogenesis of ARMs

Involvement of tryptophan hydroxylase 2 gene polymorphisms in susceptibility to tic disorder in Chinese Han population

<p>Abstract</p> <p>Background</p> <p>Tryptophan hydroxylase-2 (TPH2) is a potential candidate gene for screening tic disorder (TD).</p> <p>Methods</p> <p>A case–control study was performed to examine the association between the TPH2 gene and TD. The Sequenom® Mass ARRAY iPLEX GOLD System was used to genotype two single nucleotide polymorphisms (SNPs) of the TPH2 gene in 149 TD children and in 125 normal controls.</p> <p>Results</p> <p>For rs4565946, individuals with the TT genotype showed a significantly higher risk of TD than those with TC plus CC genotypes [odds ratio (OR) =3.077, 95% confidence interval (CI): 1.273–7.437; <it>P</it> = 0.009], as did male TD children with the TT genotype (OR = 3.228, 95% CI: 1.153–9.040; <it>P</it> = 0.020). The G allele of rs4570625 was significantly more frequent in TD children with higher levels of tic symptoms (Yale Global Tic Severity Scale, YGTSS) than those in controls among the male children (OR = 1.684, 95%: 1.097–2.583; <it>P</it> = 0.017]. TD children with severe tic symptoms had significantly higher frequencies of rs4546946 TT genotype than did normal controls in boys (OR = 3.292, 95% CI: 1.139–9.513; <it>P</it> = 0.022). We also found that genotype distributions of both SNPs were different between the Asian and European populations.</p> <p>Conclusions</p> <p>Our results indicated that the TT genotype of rs4565946 is a potential genetic risk factor for TD, and the allele G of rs4570625 might be associated with the severity of tic symptoms in boys. These polymorphisms might be susceptibility loci for TD in the Chinese Han population. Because of the confounding of co-existing attention deficit hyperactivity disorder (ADHD),these findings need to be confirmed by studies in much larger samples.</p

Identification of histone malonylation in the human fetal brain and implications for diabetes‐induced neural tube defects

Abstract Background Neural tube defects (NTDs) are severe congenital malformations. Diabetes during pregnancy is a risk factor for NTDs, but its mechanism remains elusive. Emerging evidence suggests that protein malonylation is involved in diabetes. Here, we report the correlation between histone lysine malonylation in diabetes‐induced NTDs. Methods Nano‐HPLC/MS/MS was used to screen the histone malonylation profile in human embryonic brain tissue. Then, the histone malonylation level was compared between the brains of normal control mice and mice with diabetes‐induced NTDs. Finally, the histone malonylation level was compared under high glucose exposure in an E9 neuroepithelial cell line (NE4C). Results A total of 30 histone malonylation sites were identified in human embryonic brain tissue, including 18 novel sites. Furthermore, we found an increased histone malonylation level in brain tissues from mice with diabetes‐induced NTDs. Finally, both the histone malonylation modified sites and the modified levels were proved to be increased in the NE4C treated with high glucose. Conclusion Our results present a comprehensive map of histone malonylation in the human fetal brain. Furthermore, we provide experimental evidence supporting a relationship between histone malonylation and NTDs caused by high glucose‐induced diabetes. These findings offer new insights into the pathological role of histone modifications in human NTDs

Possible Catch-Up Developmental Trajectories for Children with Mild Developmental Delay Caused by <i>NAA15</i> Pathogenic Variants

Variants in NAA15 are closely related to neurodevelopmental disorders (NDDs). In this study, we investigated the spectrum and clinical features of NAA15 variants in a Chinese NDD cohort of 769 children. Four novel NAA15 pathogenic variants were detected by whole-exome sequencing, including three de novo variants and one maternal variant. The in vitro minigene splicing assay confirmed one noncanonical splicing variant (c.1410+5G>C), which resulted in abnormal mRNA splicing. All affected children presented mild developmental delay, and catch-up trajectories were noted in three patients based on their developmental scores at different ages. Meanwhile, the literature review also showed that half of the reported patients with NAA15 variants presented mild/moderate developmental delay or intellectual disability, and possible catch-up sign was indicated for three affected patients. Taken together, our study expanded the spectrum of NAA15 variants in NDD patients. The affected patients presented mild developmental delay, and possible catch-up developmental trajectories were suggested. Studying the natural neurodevelopmental trajectories of NDD patients with pathogenic variants and their benefits from physical rehabilitations are needed in the future for precise genetic counseling and clinical management

Frequency detection of BRAF V600E mutation in a cohort of pediatric langerhans cell histiocytosis patients by next-generation sequencing

Abstract Background Langerhans cell histiocytosis (LCH) is a rare neoplastic disease that occurs in both children and adults, and BRAF V600E is detected in up to 64% of the patients. Several studies have discussed the associations between BRAF V600E mutation and clinicopathological manifestations, but no clear conclusions have been drawn regarding the clinical significance of the mutation in pediatric patients. Results We retrieved the clinical information for 148 pediatric LCH patients and investigated the BRAF V600E mutation using next-generation sequencing alone or with droplet digital PCR. The overall positive rate of BRAF V600E was 60/148 (41%). The type of sample (peripheral blood and formalin-fixed paraffin-embedded tissue) used for testing was significantly associated with the BRAF V600E mutation status (p-value = 0.000 and 0.000). The risk of recurrence declined in patients who received targeted therapy (p-value = 0.006; hazard ratio 0.164, 95%CI: 0.046 to 0.583). However, no correlation was found between the BRAF V600E status and gender, age, stage, specific organ affected, TP53 mutation status, masses close to the lesion or recurrence. Conclusions This is the largest pediatric LCH study conducted with a Chinese population to date. BRAF V600E in LCH may occur less in East Asian populations than in other ethnic groups, regardless of age. Biopsy tissue is a more sensitive sample for BRAF mutation screening because not all of circulating DNA is tumoral. Approaches with low limit of detection or high sensitivity are recommended for mutation screening to avoid type I and II errors

Neurodevelopmental trajectory and modifiers of 16p11.2 microdeletion: A follow‐up study of four Chinese children carriers

Abstract Background Neurodevelopmental disorders (NDDs) are a group of disorders with high genetic and phenotypic heterogeneities. The 16p11.2 microdeletion has been implicated as an important genetic risk factor for NDDs. Methods Multiple genetic tests were used to detect the 16p11.2 microdeletion from 918 Chinese children with NDDs. Targeted sequencing of genes in the 16p11.2 interval was performed in all carriers of the 16p11.2 microdeletion, and whole‐genome expression profiling analysis was performed for the patient carriers and normal carriers in their intra‐family. Results Three patients carrying the 16p11.2 microdeletion were screened out, indicating a frequency of 0.33% for the 16p11.2 microdeletion in this cohort. We reviewed the neurodevelopmental trajectories of the 16p11.2 microdeletion carriers from childhood to puberty and confirmed that this microdeletion was associated with abnormal neurodevelopment, with varied neurodevelopmental phenotypes. A differential PRRT2 genotype (rs10204, T>C) was identified between patients and normal carriers of the 16p11.2 microdeletion. Moreover, the determination of differential whole‐genome expression profiling demonstrated the destruction of the top‐ranked network in neurogenesis and accounted for observation of abnormal neurodevelopmental phenotypes in the 16p11.2 microdeletion carriers. Conclusions We have provided the frequency of the 16p11.2 microdeletion in a Chinese pediatric NDD cohort with a variable NDD phenotype from childhood to puberty, which is useful for Chinese geneticists/pediatricians to conduct the 16p11.2 microdeletion testing in children with NDDs

Additional file 1 of Effect of cognitive-behavior therapy for children with functional abdominal pain: a meta-analysis

Supplementary Material

Pensamiento social chino sobre América Latina

Hoy en día, las relaciones de China con el mundo están experimentando profundos cambios sin precedentes, lo que se refleja principalmente en dos aspectos. En primer lugar, China se encuentra en un período crucial de mejorar la calidad de la reforma y del desarrollo. Si da un paso adelante, podrá realizar el objetivo de construir una sociedad acomodada de manera integral, podrá atravesar la trampa del ingreso medio, el ingreso nacional pasará del nivel bajo al medio en las filas de los países de ingresos medios y altos, y se revelará aún más la superioridad de la teoría, el sistema y la cultura del camino del socialismo con peculiaridades chinas. Si continúa avanzando, podrá lograr el segundo objetivo centenario y materializar el sueño chino de la gran revitalización de la nación china. Nos encontramos en un gran momento, así como en una gran era, en la que se requiere tener un valor extraordinario y un esfuerzo excepcional. En segundo lugar, China está acercándose al centro del escenario mundial. El hecho de que un país socialista en vías de desarrollo como China entre al centro del escenario mundial tiene una inevitabilidad histórica, es decir, sucederá tarde o temprano. Pero también tiene una contingencia, que consiste en que desde 2008, debido al profundo impacto de la crisis financiera internacional, Estados Unidos y otros países occidentales comenzaron una recuperación lenta; sin embargo, no han logrado tener mucho éxito y su influencia internacional viene disminuyendo. Mientras tanto, China aprovecha la oportunidad para seguir adelante y ha aumentado significativamente su influencia internacional. No obstante, nos queda mucho por hacer para consolidar dicha situación y tenemos que esforzarnos más para hacerla irreversible. La clave consiste en superar el talón de Aquiles en la innovación, resolver absolutamente las principales contradicciones, y evitar la trampa de Tucídides en la relación entre las principales potencias. Solo así se podrá garantizar que nada detenga la tendencia del desarrollo en general de China, incluso después de que Estados Unidos y otros países occidentales se recuperen completamente. Se requiere una lucha larga y difícil para conseguir un contexto internacional favorable para China. Y es necesario hacer más esfuerzos para consolidarlo. El futuro desarrollo de China depende de cinco aspectos, los cuales pueden ser resumidos en los siguientes ejes temáticos

Pensamiento social chino sobre América Latina

Hoy en día, las relaciones de China con el mundo están experimentando profundos cambios sin precedentes, lo que se refleja principalmente en dos aspectos. En primer lugar, China se encuentra en un período crucial de mejorar la calidad de la reforma y del desarrollo. Si da un paso adelante, podrá realizar el objetivo de construir una sociedad acomodada de manera integral, podrá atravesar la trampa del ingreso medio, el ingreso nacional pasará del nivel bajo al medio en las filas de los países de ingresos medios y altos, y se revelará aún más la superioridad de la teoría, el sistema y la cultura del camino del socialismo con peculiaridades chinas. Si continúa avanzando, podrá lograr el segundo objetivo centenario y materializar el sueño chino de la gran revitalización de la nación china. Nos encontramos en un gran momento, así como en una gran era, en la que se requiere tener un valor extraordinario y un esfuerzo excepcional. <br> En segundo lugar, China está acercándose al centro del escenario mundial. El hecho de que un país socialista en vías de desarrollo como China entre al centro del escenario mundial tiene una inevitabilidad histórica, es decir, sucederá tarde o temprano. Pero también tiene una contingencia, que consiste en que desde 2008, debido al profundo impacto de la crisis financiera internacional, Estados Unidos y otros países occidentales comenzaron una recuperación lenta; sin embargo, no han logrado tener mucho éxito y su influencia internacional viene disminuyendo. Mientras tanto, China aprovecha la oportunidad para seguir adelante y ha aumentado significativamente su influencia internacional. No obstante, nos queda mucho por hacer para consolidar dicha situación y tenemos que esforzarnos más para hacerla irreversible. La clave consiste en superar el “talón de Aquiles” en la innovación, resolver absolutamente las principales contradicciones, y evitar la “trampa de Tucídides” en la relación entre las principales potencias. Solo así se podrá garantizar que nada detenga la tendencia del desarrollo en general de China, incluso después de que Estados Unidos y otros países occidentales se recuperen completamente. Se requiere una lucha larga y difícil para conseguir un contexto internacional favorable para China. Y es necesario hacer más esfuerzos para consolidarlo. El futuro desarrollo de China depende de cinco aspectos, los cuales pueden ser resumidos en los siguientes ejes temáticos