Dietary intake and gastrointestinal symptoms are altered in children with Autism Spectrum Disorder: the relative contribution of autism-linked traits.

BACKGROUND: Dietary and gastrointestinal (GI) problems have been frequently reported in autism spectrum disorder (ASD). However, the relative contributions of autism-linked traits to dietary and GI problems in children with ASD are poorly understood. This study firstly compared the dietary intake and GI symptoms between children with ASD and typically developing children (TDC), and then quantified the relative contributions of autism-linked traits to dietary intake, and relative contributions of autism-linked traits and dietary intake to GI symptoms within the ASD group. METHODS: A sample of 121 children with ASD and 121 age-matched TDC were eligible for this study. The dietary intake indicators included food groups intakes, food variety, and diet quality. The autism-linked traits included ASD symptom severity, restricted repetitive behaviors (RRBs), sensory profiles, mealtime behaviors, and their subtypes. Linear mixed-effects models and mixed-effects logistic regression models were used to estimate the relative contributions. RESULTS: Children with ASD had poorer diets with fewer vegetables/fruits, less variety of food, a higher degree of inadequate/unbalanced dietary intake, and more severe constipation/total GI symptoms than age-matched TDC. Within the ASD group, compulsive behavior (a subtype of RRBs) and taste/smell sensitivity were the only traits associated with lower vegetables and fruit consumption, respectively. Self-injurious behavior (a subtype of RRBs) was the only contributing trait to less variety of food. Limited variety (a subtype of mealtime behavior problems) and ASD symptom severity were the primary and secondary contributors to inadequate dietary intake, respectively. ASD symptom severity and limited variety were the primary and secondary contributors to unbalanced dietary intake, respectively. Notably, unbalanced dietary intake was a significant independent factor associated with constipation/total GI symptoms, and autism-linked traits manifested no contributions. CONCLUSIONS: ASD symptom severity and unbalanced diets were the most important contributors to unbalanced dietary intake and GI symptoms, respectively. Our findings highlight that ASD symptom severity and unbalanced diets could provide the largest benefits for the dietary and GI problems of ASD if they were targeted for early detection and optimal treatment.

Associations between maternal exposure to air pollution during pregnancy and trajectories of infant growth: A birth cohort study.

OBJECTIVE: We examined the relationships between infants' growth trajectories and prenatal exposure to air pollution, which is still under-investigated. METHODS: A birth cohort study was constructed using medical records of pregnant women and infants born between 2015 and 2019 in Foshan, China. Using satellite-based spatial-temporal models, prenatal exposure to air pollutants including particulate matter with an aerodynamic dimension of < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) was assessed at each woman's residence. Latent class growth modeling was used to identify trajectories of physical (body length and weight) growth and neurodevelopment, which were repeatedly measured within 1 year after birth. Logistic regression models were used to investigate the associations between prenatal exposure to air pollution and the risks of growth disorders, adjusting for an array of potential confounders. RESULTS: We identified two growth trajectories for body length [normal: 3829 (93%); retardation: 288 (7%)], three for weight [normal: 2475 (59.6%); retardation: 390 (9.4%); overgrowth: 1287 (31%)], and two for neurodevelopment [normal: 956 (66.1%); retardation: 491 (33.9%)]. For exposure over whole pregnancy, SO2 was associated with an increased risk of body length retardation (OR for per 1 µg/m3 increment: 1.09, 95%CI: 1.01-1.17); PM2.5 (OR: 1.05, 95%CI: 1.03-1.07), SO2 (OR: 1.15, 95%CI: 1.08-1.22), and NO2 (OR: 1.05, 95%CI: 1.03-1.07) were positively associated with neurodevelopmental retardation. Such associations appeared stronger for exposures over the first and second trimesters. No significant associations were detected for weight growth. CONCLUSIONS: Maternal exposure to air pollution during pregnancy was associated with higher risks of impairments in both physical growth, particularly body length, and neurodevelopment.

Multi-omics analyses demonstrate the modulating role of gut microbiota on the associations of unbalanced dietary intake with gastrointestinal symptoms in children with autism spectrum disorder.

Our previous work revealed that unbalanced dietary intake was an important independent factor associated with constipation and gastrointestinal (GI) symptoms in children with autism spectrum disorder (ASD). Growing evidence has shown the alterations in the gut microbiota and gut microbiota-derived metabolites in ASD. However, how the altered microbiota might affect the associations between unbalanced diets and GI symptoms in ASD remains unknown. We analyzed microbiome and metabolomics data in 90 ASD and 90 typically developing (TD) children based on 16S rRNA and untargeted metabolomics, together with dietary intake and GI symptoms assessment. We found that there existed 11 altered gut microbiota (FDR-corrected P-value <0.05) and 397 altered metabolites (P-value <0.05) in children with ASD compared with TD children. Among the 11 altered microbiota, the Turicibacter, Coprococcus 1, and Lachnospiraceae FCS020 group were positively correlated with constipation (FDR-corrected P-value <0.25). The Eggerthellaceae was positively correlated with total GI symptoms (FDR-corrected P-value <0.25). More importantly, three increased microbiota including Turicibacter, Coprococcus 1, and Eggerthellaceae positively modulated the associations of unbalanced dietary intake with constipation and total GI symptoms, and the decreased Clostridium sp. BR31 negatively modulated their associations in ASD children (P-value <0.05). Together, the altered microbiota strengthens the relationship between unbalanced dietary intake and GI symptoms. Among the altered metabolites, ten metabolites derived from microbiota (Turicibacter, Coprococcus 1, Eggerthellaceae, and Clostridium sp. BR31) were screened out, enriched in eight metabolic pathways, and were identified to correlate with constipation and total GI symptoms in ASD children (FDR-corrected P-value <0.25). These metabolomics findings further support the modulating role of gut microbiota on the associations of unbalanced dietary intake with GI symptoms. Collectively, our research provides insights into the relationship between diet, the gut microbiota, and GI symptoms in children with ASD.

Association between maternal parenting styles and behavioral problems in children with ASD: Moderating effect of maternal autistic traits.

Background: Children with autism spectrum disorder (ASD) are at high risk of experiencing externalizing and internalizing problems. This study aimed to reveal how maternal parenting styles and autistic traits influence behavioral problems in children with ASD. Methods: This study recruited 70 2-5 years children with ASD and 98 typically developing (TD) children. The Parental Behavior Inventory (PBI) and Autism Spectrum Quotient (AQ) were used to collect the maternal parenting styles and autistic traits, respectively. The children's behavioral problems were reported by the mothers using the Strengths and Difficulties Questionnaire (SDQ). Hierarchical moderated regression analyses were used to determine whether maternal autistic traits moderated the association between parenting style and behavioral problems in the children. Results: Compared to TD children, children with ASD exhibited more severe externalizing and internalizing problems (t = 4.85, p < 0.01). The ASD group scored lower in the maternal supportive/engaged parenting style than the TD group (t = 3.20, p < 0.01). In the TD group, the maternal AQ attention switching domain was positively correlated with internalizing problems in the children (ß = 0.30, p = 0.03). In the ASD group, hostile/coercive parenting style was significantly correlated with externalizing problems in the children (ß = 0.30, p = 0.02), whereas maternal AQ attention switching domain was negatively correlated with externalizing problems (ß = -0.35, p = 0.02). Moreover, the maternal AQ attention switching domain moderated the association between hostile/coercive parenting style and children's externalizing problems (ß = 0.33, p = 0.04). Conclusion: Among ASD children, a hostile/coercive parenting style can increase the risks of children's externalizing problems, especially in the context of high levels of maternal attention-switching problems. Hence, the current study has important implications for the clinical practice of early family-level interventions for children with ASD.

Relationship of Early Anemia with Neurodevelopment and Brain Injury in Very Low Birth Weight Preterm Infants-A Prospective Cohort Study.

Anemia is associated with neurodevelopmental delays and brain injury in infants and toddlers, but whether early anemia has a similar effect in neonatal preterm infants is largely unknown. Thus, this study aimed to determine the relationship of early anemia with neurodevelopment and brain injury in very-low-birth-weight (VLBW) preterm infants within the neonatal period. A prospective cohort study including 110 VLBW preterm infants was conducted in Southern China from 2016 to 2018. All participants were followed from birth to 1 month corrected age. Early anemia is defined as hemoglobin of ≤145 g/L within the first week after birth. The non-anemic group (control group, N = 55) was 1:1 matched with the early anemia group (N = 55) according to birth weight and gestational age. Neurodevelopment at 1 month corrected age and brain injury within 1 month corrected age were measured by neonatal behavioral neurological assessments (NBNA) and cranial ultrasound, respectively. Compared to the control group, the early anemia group had a lower score in behavioral ability in the NBNA test [11 (10-12) vs. 10 (9.5-11), p = 0.033]. Early anemia was negatively associated with the NBNA total score (ß= -0.680, 95% CI: -1.300, -0.059), especially with the behavioral ability score (ß= -0.504, 95% CI: -0.941, -0.067) after adjusting for the confounders. However, no association between early anemia and brain injury was observed. In conclusion, in VLBW preterm infants, early anemia is negatively correlated with neurodevelopment, especially with behavioral ability.

The Development and Evaluation of the Nutritional Risk Screening Tool for Preterm Infants from Birth to Corrected Age Four Months Old: A Pilot Study.

INTRODUCTION: Premature infants are exceptionally vulnerable to nutrition-related diseases, and the utilization of standardized feeding guidelines may reduce nutritional practice variation, which can promote growth. Nutritional risk screening is the first step for standardized nutrition advice. However, risk screening tools specific for following up preterm infants are scarce. Hence, our study aimed to develop and evaluate a standardized Nutritional Risk Screening Tool for Preterm Infants (NRSP subscale 1) from birth to corrected age four months old . METHODS: This study was a two-phase (the development phase and evaluation phase) study. Initially, we used the Delphi expert consultation method to create NRSP subscale 1. Then, a professional panel interviewed the participated preterm infants using the screening tool, measured anthropometric parameters, and conducted an intellectual development test on the interview day and remeasured anthropometric parameters 2 weeks or 1 month after the first interview. In the development phase, we cross-tabulated the responses to the screening tool with the classifications of z-scores of the body weight, length, or head circumference to identify significant predictors of underweight, stunting, or microcephaly. We then combined significant predictors to produce models for predicting underweight, stunting, or microcephaly by multivariate logistic regression analysis. In the evaluation phase, the area under the curve (AUC), sensitivity, specificity, and correlation coefficient by Spearman's correlation analysis (rs) between the risk classifications by NRSP subscale 1 and the classifications of the z-scores of the body weight, length, or head circumference were calculated to assess the validity of the screening tool. Intellectual development levels between high and low nutritional risk infants were statistically compared. RESULTS: A total of 219 and 244 preterm infants were included to two phases, respectively. AUC was 0.936 (95% CI: 0.860-1.000, p < 0.001), sensitivity was 0.667, specificity was 0.941, rs = 0.407 (p < 0.001); AUC was 0.794 (95% CI: 0.638-0.951, p = 0.002), sensitivity was 0.500, specificity was 0.953, rs = 0.339 (p < 0.001); AUC was 0.831 (95% CI: 0.737-0.925, p = 0.001), sensitivity was 0.889, specificity was 0.643, rs = 0.215 (p = 0.001) in predicting underweight, stunting, and microcephaly on the interview day, respectively. AUC was 0.905 (95% CI: 0.826-0.984, p = 0.006), sensitivity was 0.500, specificity was 0.905, rs = 0.504 (p < 0.001); AUC was 0.738 (95% CI: 0.515-0.960, p = 0.034), sensitivity was 0.429, specificity was 0.848, rs = 0.382 (p < 0.001); AUC was 0.664 (95% CI: 0.472-0.856, p = 0.071), sensitivity was 0.455, specificity was 0.809, rs = 0.169 (p = 0.037) in predicting underweight, stunting, and microcephaly 2 weeks or 1 month after the first interview, respectively. Gross motor development quotients (DQs) (95.85 [32.87] vs. 86.29 [17.19], p = 0.022), fine motor DQs (115.77 [46.03] vs. 102.12 [20.27], p = 0.010), and verbal DQs (110.73 [35.27] vs. 100.63 [21.28], p = 0.042) were higher in low nutritional risk infants than high-risk ones. CONCLUSION: NRSP subscale 1 was acceptable and reliable in predicting underweight, but the validity in predicting stunting or microcephaly was slightly mild. Further investigations are required to authenticate NRSP subscale 1's effectiveness.

Prenatal Progestin Exposure-Mediated Oxytocin Suppression Contributes to Social Deficits in Mouse Offspring.

Epidemiological studies have shown that maternal hormone exposure is associated with autism spectrum disorders (ASD). The hormone oxytocin (OXT) is a central nervous neuropeptide that plays an important role in social behaviors as well as ASD etiology, although the detailed mechanism remains largely unknown. In this study, we aim to investigate the potential role and contribution of OXT to prenatal progestin exposure-mediated mouse offspring. Our in vitro study in the hypothalamic neurons that isolated from paraventricular nuclei area of mice showed that transient progestin exposure causes persistent epigenetic changes on the OXT promoter, resulting in dissociation of estrogen receptor ß (ERß) and retinoic acid-related orphan receptor α (RORA) from the OXT promoter with subsequent persistent OXT suppression. Our in vivo study showed that prenatal exposure of medroxyprogesterone acetate (MPA) triggers social deficits in mouse offspring; prenatal OXT deficiency in OXT knockdown mouse partly mimics, while postnatal ERß expression or postnatal OXT peptide injection partly ameliorates, prenatal MPA exposure-mediated social deficits, which include impaired social interaction and social abilities. On the other hand, OXT had no effect on prenatal MPA exposure-mediated anxiety-like behaviors. We conclude that prenatal MPA exposure-mediated oxytocin suppression contributes to social deficits in mouse offspring.

Hematopoietic stem cell transplantation ameliorates maternal diabetes-mediated gastrointestinal symptoms and autism-like behavior in mouse offspring.

Epidemiological studies have shown that maternal diabetes is associated with autism spectrum disorder development, although the detailed mechanism remains unclear. We have previously found that maternal diabetes induces persistent epigenetic changes and gene suppression in neurons, subsequently triggering autism-like behavior (ALB). In this study, we investigated the potential role and effect of hematopoietic stem cells (HSCs) on maternal diabetes-mediated gastrointestinal (GI) dysfunction and ALB in a mouse model. We show in vitro that transient hyperglycemia induced persistent epigenetic changes and gene suppression of tight junction proteins. In vivo, maternal diabetes-mediated oxidative stress induced gene suppression and inflammation in both peripheral blood mononuclear cells and intestine epithelial cells, subsequently triggering GI dysfunction with increased intestinal permeability and altered microbiota compositions, as well as suppressed gene expression in neurons and subsequent ALB in offspring; HSC transplantation (HSCT) ameliorates this effect by systematically reversing maternal diabetes-mediated oxidative stress. We conclude that HSCT can ameliorate maternal diabetes-mediated GI symptoms and autism-like behavior in mouse offspring.

Maternal diabetes-mediated RORA suppression in mice contributes to autism-like offspring through inhibition of aromatase.

Retinoic acid-related orphan receptor alpha (RORA) suppression is associated with autism spectrum disorder (ASD) development, although the mechanism remains unclear. In this study, we aim to investigate the potential effect and mechanisms of RORA suppression on autism-like behavior (ALB) through maternal diabetes-mediated mouse model. Our in vitro study in human neural progenitor cells shows that transient hyperglycemia induces persistent RORA suppression through oxidative stress-mediated epigenetic modifications and subsequent dissociation of octamer-binding transcription factor 3/4 from the RORA promoter, subsequently suppressing the expression of aromatase and superoxide dismutase 2. The in vivo mouse study shows that prenatal RORA deficiency in neuron-specific RORA null mice mimics maternal diabetes-mediated ALB; postnatal RORA expression in the amygdala ameliorates, while postnatal RORA knockdown mimics, maternal diabetes-mediated ALB in offspring. In addition, RORA mRNA levels in peripheral blood mononuclear cells decrease to 34.2% in ASD patients (n = 121) compared to the typically developing group (n = 118), and the related Receiver Operating Characteristic curve shows good sensitivity and specificity with a calculated 84.1% of Area Under the Curve for ASD diagnosis. We conclude that maternal diabetes contributes to ALB in offspring through suppression of RORA and aromatase, RORA expression in PBMC could be a potential marker for ASD screening.

Prenatal exposure to air pollution and neurodevelopmental delay in children: A birth cohort study in Foshan, China.

BACKGROUND: Prenatal exposure to air pollution may have adverse effects on neurodevelopment in children, but epidemiological evidence remains inconclusive. OBJECTIVE: To investigate the associations between prenatal air pollution exposure and neurodevelopmental delay. METHODS: We conducted a birth cohort study based on pregnancy and birth registry in Foshan, China. Exposure to particulate matter of aerodynamic diameter < 1 µm, 2.5 µm, 10 µm (PM1, PM2.5, PM10), nitrogen dioxide (NO2) and sulfur dioxide (SO2) over pregnancy (trimester 1, 2, 3 and entire pregnancy) was estimated at each woman's residential address using spatial-temporal models. Neurodevelopmental assessment was performed by pediatricians using a five-domain scale and developmental quotient (DQ) was calculated as a global measure. Logistic regression models were used to investigate the associations between prenatal air pollution exposure and neurodevelopmental delay (DQ < 75) with adjustment for potential confounders. RESULTS: We included 15,778 child-mother pairs in this analysis, including 1013 children with neurodevelopmental delay. We observed positive associations between prenatal exposure to air pollution and higher risk of neurodevelopmental delay in children. The adjusted odds ratios (ORs) per 10 µg/m3 elevation in PM1, PM2.5, PM10, NO2 and SO2 in entire pregnancy were 1.12 [95% confidence interval (CI): 1.01, 1.25], 1.15 (95% CI: 1.03, 1.29), 1.12 (95% CI: 1.02, 1.24), 1.06 (95% CI: 0.94, 1.19) and 1.58 (95% CI: 1.11, 2.23), respectively. The associations were more robust for trimester 1 and trimester 2, especially trimester 1. CONCLUSIONS: Exposure to air pollution during pregnancy, especially early-to-mid pregnancy, was associated with increased risk of neurodevelopmental delay in young children, indicating its adverse neurodevelopmental effects in early-life stage.

Impact of the COVID-19 Pandemic on Children with ASD and Their Families: An Online Survey in China.

BACKGROUND: The COVID-19 pandemic and lockdown will have short-term and long-term psychosocial and mental health implications for children. Children with autism may have some specific needs for support because of their difficulties in social communication, stereotyped behavior patterns, and other specificities brought about by autism. PURPOSE: The purpose of this study was to investigate the impact of the COVID-19 pandemic on ASD children and their families. PATIENTS AND METHODS: A total of 406 parents of ASD children completed an online survey investigating basic information; sleep, outdoor activities, and rehabilitation training; ASD children's frequency of abnormal behaviors; and stress and emotional status of parents. RESULTS: 50.3% of the parents thought their children had sleep problems, and 47.3% of the parents thought their children's outdoor activity time was reduced. About 40% of parents think that their children have improved cognitive ability, language expression, and understanding. 36.2% of the families reported that their children's emotional and social performance became worse. 60.8% of parents reported that their children's training intensity decreased. The most common abnormal behaviors observed in children with ASD were being easily distracted, losing temper, and crying. 81.3% of parents did not have anxiety, but 98% of parents reported that family training was under pressure. CONCLUSION: The main impact of the COVID-19 pandemic on children with ASD is that they do not have access to professional rehabilitation training. These families need more medical support, especially in family training, to help parents improve the social and emotional control skills of ASD children.

Association of Breastfeeding for the First Six Months of Life and Autism Spectrum Disorders: A National Multi-Center Study in China.

Previous studies have shown that exclusive breastfeeding is associated with lower odds of having autism spectrum disorders (ASD) in children, but data are lacking in Asian countries, especially China. This cross-sectional study of seven cities in China collected data from August 2016 to March 2017 from 6049 toddlers aged 16-30 months and their parents who responded to questionnaires. The breastfeeding status was collected via questionnaires based on recommendations from the World Health Organization. The standard procedure for screening and diagnosis was applied to identify toddlers with ASD. Among the 6049 toddlers (3364 boys [55.6%]; mean [SD] age, 22.7 [4.1] months), 71 toddlers (1.2%) were identified as ASD. The prevalence of exclusive breastfeeding, partial breastfeeding, and not breastfeeding was 48.8%, 42.2%, and 9.1%, respectively. Compared to toddlers with exclusive breastfeeding, toddlers with partial breastfeeding or without breastfeeding had higher odds of having ASD (odd ratios [OR]: 1.55, 95% confidence interval [CI]: 0.90-2.74; OR: 2.34, 95% CI: 1.10-4.82). We did not find significant modification of demographic characteristics on the associations. The results remained robust in multiple sensitivity analyses. Toddlers without breastfeeding for the first six months of life had higher odds of having ASD, and our findings shed light on the necessity of strengthening public health efforts to increase exclusive breastfeeding in China.

Vitamin D deficiency worsens maternal diabetes induced neurodevelopmental disorder by potentiating hyperglycemia-mediated epigenetic changes.

Many studies have shown that vitamin D (VD) deficiency may be a risk factor for neurodevelopmental disorders, such as autism spectrum disorders (ASDs) and schizophrenia, although causative mechanisms remain unknown. In this study, we investigated the potential role and effect of VD on maternal diabetes induced autism-related phenotypes. The in vitro study found that enhancing genomic VD signaling by overexpressing the VD receptor (VDR) in human neural progenitor cells ACS-5003 protects against hyperglycemia-induced oxidative stress and inflammation by activating Nrf2 and its target genes, including SOD2 and HMOX1, and accordingly, VDR gene knockdown worsens the problem. In the two in vivo models we explored, maternal diabetes was used to establish an animal model of relevance to ASD, and mice lacking 25-hydroxyvitamin D 1-alpha-hydroxylase (the rate-limiting enzyme in the synthesis of 1,25(OH)2D3) were used to develop a model of VD deficiency (VDD). We show that although prenatal VDD itself does not produce ASD-relevant phenotypes, it significantly potentiates maternal diabetes induced epigenetic modifications and autism-related phenotypes. Postnatal manipulation of VD has no effect on maternal diabetes induced autism-related phenotypes. We conclude that VDD potentiates maternal diabetes induced autism-related phenotypes in offspring by epigenetic mechanisms. This study adds to other preclinical studies linking prenatal VDD with a neurodevelopmental disorder.

Low vitamin D status is associated with obesity but no other cardiovascular risk factors in Chinese children and adolescents.

BACKGROUND AND AIMS: Evidence on relationship between vitamin D status and cardiovascular health in childhood remains inconsistent. This study aimed to investigate vitamin D status and its relationship with cardiovascular risk factors in Chinese children and adolescents. METHODS AND RESULTS: Cross-sectional data were obtained from 2680 children and adolescents aged 7-18 y in Guangzhou, South China. Anthropometric and socioeconomic characters, concentration of serum 25-hydroxyvitamin D [25(OH)D], fasting blood glucose and lipids, as well as information about diet and physical activity were measured and collected. Logistic regression model was adopted to analyze the associations between 25(OH)D levels and cardiovascular risk factors including obesity, high blood pressure, dyslipidemia, hyperglycemia, and metabolic syndrome. Overall, median level of 25(OH)D was 19.74 ng/mL. The prevalence rates of vitamin D deficiency and inadequacy were 7.5% and 44.4%, both of which were highest among adolescents aged 14-18 y (14.5% and 51.6%, respectively). As vitamin D level increased, an upward trend in fasting glucose concentrations was observed in subjects with normal fasting glucose level, but not in subjects with hyperglycemia. Among the assessed cardiovascular risk factors, vitamin D status was only inversely associated with general obesity, and the adjusted odds ratio was 1.95 (95% CI: 1.08-3.49), comparing the lowest 25(OH)D quartile with the highest one. CONCLUSIONS: Vitamin D deficiency and inadequacy remain a concern among school-aged children and adolescents in Guangzhou, South China, particularly in adolescents aged 14-18 y. However, low vitamin D status was found only associated with general obesity but no other cardiovascular risk factors.

Potential role of genomic imprinted genes and brain developmental related genes in autism.

BACKGROUND: Autism is a complex disease involving both environmental and genetic factors. Recent efforts have implicated the correlation of genomic imprinting and brain development in autism, however the pathogenesis of autism is not completely clear. Here, we used bioinformatic tools to provide a comprehensive analysis of the autism-related genes, genomic imprinted genes and the spatially and temporally differentially expressed genes of human brain, aiming to explore the relationship between autism, brain development and genomic imprinting. METHODS: This study analyzed the distribution correlation between autism-related genes and imprinted genes on chromosomes using sliding windows and statistical methods. The normal brains' gene expression microarray data were reanalyzed to construct a spatio-temporal coordinate system of gene expression during brain development. Finally, we intersected the autism-related genes, imprinted genes and brain spatio-temporally differentially expressed genes for further analysis to find the major biological processes that these genes involved. RESULTS: We found a positive correlation between the autism-related genes' and imprinted genes' distribution on chromosomes. Through the analysis of the normal brain microarray data, we constructed a spatio-temporal coordinate system of gene expression during human brain development, and obtained 13 genes that are differentially expressed in the process of brain development, which are both autism-related genes and imprinted genes. Furthermore, enrichment analysis illustrated that these genes are mainly involved in the biological processes, such as gamma-aminobutyric acid signaling pathway, neuron recognition, learning or memory, and regulation of synaptic transmission. Bioinformatic analysis implied that imprinted genes regulate the development and behavior of the brain. And its own mutation or changes in the epigenetic modification state of the imprinted control region could lead to some diseases, indicating that imprinted genes and brain development play an important role in diagnosis and prognosis of autism. CONCLUSION: This study systematically correlates brain development and genomic imprinting with autism, which provides a new perspective for the study of genetic mechanisms of autism, and selected the potential candidate biomarkers for early diagnosis of autism in clinic.

Reliability and Validity of the Chinese Version of Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT-R/F).

Although early detection of autism facilitates intervention, early detection strategies are not yet widespread in China. To improve the situation, the Chinese version of the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) was validated. The sample included 7928 toddlers, aged 16 to 30 months, screened during their routine care in six provinces of China. When the cut-off value was 3, the sensitivity and specificity of M-CHAT-R were 0.963 and 0.865. The inter-rater reliability and the test-retest reliability were also adequate (intraclass correlation coefficients were 0.853 and 0.759, both ps < .01). The Chinese version of M-CHAT-R/F is an effective tool for early detection of ASD and is applicable to early screening in China.

Cyclo-oxygenase-2 promotes migration and invasion of breast cancer MDA-MB231 cells by regulating EMT / 中国肿瘤生物治疗杂志

@#Objective:To investigate the role of cyclo-oxygenase-2 (COX-2) in breast cancer metastasis and its possible mechanism. Methods: A total of 45 cases of primary breast cancer tissues and brain metastatic breast cancer tissues were collected from patients, who underwent mastectomy in Yunnan Cancer Hospital from October 2015 to April 2018, including 30 cases of primary lesions and 15 cases of brain metastasis. qPCR was used to detect the expression of COX-2 in breast cancer tissues and brain metastatic breast cancer tissues. Recombinant viruses with COX-2 over-expression (LV6-COX2) or COX-2 knockdown (LV3-COX2 shRNA1, LV3-COX2 shRNA2) were transfected into human breast cancer MDA-MB-231 cells; After obtaining the stable expression cell lines, the effect of COX-2 expression on the proliferation of MDA-MB-231 cells was detected by CCK-8, and the effects of COX-2 expression on the migration and invasion of MDA-MB-231 cells were detected by scratch test and Transwell assay, respectively. The mRNAand protein expressions of COX-2 in each group were examined by qPCR and WB, respectively. The effect of COX-2 expression on the expression of EMT-related genes in MDA-MB-231 cells was analyzed by qPCR. Results: The expression of COX-2 in tissues of patients with brain metastases was significantly higher than that in patients with primary breast cancer tissues (P<0.01), and it was correlated with tumor TMN stage in breast cancer patients. MDA-MB-231 cell lines with stable COX-2 over-expression/knockout were successfully constructed. Over-expression of COX-2 promoted the migration and invasion of MDA-MB-231 cells (all P<0.01), and significantly increased the expressions of MMP2, MMP1, N-cadherin and vimentin (all P<0.01), but exerted insignificant effect on cell proliferation. The effect of COX-2 silence exerted the opposite effect and promoted cell proliferation (P<0.05). Conclusion: COX-2 is highly expressed in brain metastatic breast cancer tissues, which may promote the migration and invasion of breast cancer MDA-MB-231 cells by regulating EMT processes.