Association of feeding patterns in infancy with later autism symptoms and neurodevelopment: a national multicentre survey.

BACKGROUND: We aimed to compare differences in infant feeding patterns (breastfeeding and complementary food supplementation) between children with the autism spectrum disorder (ASD) and typically developing (TD) children through a multicentre study. The relationship between these patterns and later core symptoms and neurodevelopment in children with ASD was also investigated. METHODS: We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms. RESULTS: Children with ASD had a shorter breastfeeding duration in infancy (8 (3-12) months vs. 10 (6-14) months, P < 0.001), later introduction of complementary foods (P < 0.001), and poorer acceptance of complementary foods (P < 0.001) than TD children. Total ABC and CARS scores were lower in the group of children with ASD who had been breastfed for 12 months or more than in the group who had been breastfed for less than 6 months. Children with ASD who were given complementary food after 6 months had lower general quotient (GQ), adaptive ability, fine motor and language scores than those who were given complementary food within 4-6 months. Children with ASD with poor acceptance of complementary foods had higher ABC and SRS scores and lower gross motor scores than those who had good acceptance. CONCLUSIONS: Children with ASD have a shorter duration of breastfeeding, a later introduction of complementary foods, and poorer acceptance of complementary foods than TD children. These feeding patterns may be related to the symptoms and growth of children with ASD. The research suggests that continued breastfeeding for longer than 12 months may be beneficial in reducing ASD symptoms and that infants who have difficulty introducing complementary foods should be followed up for neurodevelopment. TRIAL REGISTRATION: The ethics committee of the Children's Hospital of Chongqing Medical University approved the study. Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194, registered on 23/03/2020).

Neurodevelopmental domain characteristics and their association with core symptoms in preschoolers with autism spectrum disorder in China: a nationwide multicenter study.

BACKGROUND: Autism spectrum disorder (ASD) is a group of clinically heterogenic neurodevelopmental disorders, with intellectual disability being one of its common comorbidities. No large-sample, multicenter study has focused on the neurodevelopmental aspect of preschoolers with ASD. This study investigated the neurodevelopmental characteristics of preschoolers with ASD in China and explored the association between them and the core symptoms. METHODS: We enrolled 1019 ASD preschoolers aged 2-7 years old from 13 cities around China between May 2018 and December 2019, and used the revised Children Neuropsychological and Behavior Scale (CNBS-R2016) to assess their neurodevelopment. Their autistic core behaviors were evaluated based on their Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and communication warning behavior (CWB) scores in the CNBS-R2016. RESULTS: Based on general developmental quotient (GQ) < 70, 68.4% of the preschoolers with ASD had a developmental delay (DD), rated mild in 32.7% of them. The highest DD rate (> 70%) was found in language and personal-social skills, followed by fine motor skills (68.9%). Gross motor skills had the lowest DD rate (34.0%). We found that fine motor, language, and personal-social developmental quotients (DQs) were significantly lower than gross motor skills in no DD (GQ > 70), mild DD (GQ 55-69), and moderate and below DD groups (GQ ≤ 54). Furthermore, the DQs for language and personal-social skills were significantly lower than for gross and fine motor skills in both DD groups. The ABC, SRS, CARS, and CWB scores in the no DD group were the lowest, moderate in the mild DD group, and highest in the moderate and below DD group. Besides, negative correlations were found between the DQs of the four domains and the ABC, SRS, CARS, and CWB scores, of which the language and personal-social skills DQs had the strongest correlations. CONCLUSIONS: Preschoolers with ASD had unbalanced neurodevelopment domain patterns and their neurodevelopmental levels were negatively correlated with the autism core symptoms. Hence, pediatricians should actively evaluate the neurodevelopment of children with ASD and conduct long-term follow-up during their early childhood to promote early diagnosis and develop personalized intervention plans. TRIAL REGISTRATION: ChiCTR2000031194 , registered on 03/23/2020.

Whole-exome sequencing analysis to identify novel potential pathogenetic NPC1 mutations in two Chinese families with Niemann-Pick disease type C.

BACKGROUND: Niemann-Pick disease type C (NPC) is an autosomal recessive lipid storage disorder, affecting the nervous system and the internal organs. It is characterized by the presence of foam cells in bone marrow, liver, and spleen biopsies. Although many mutations in NPC1 have been identified to be related to disease onset, the relationship between genotype and phenotype remains unclear. To elucidate the genetic heterogeneity of NPC, we described the clinical manifestations and possible genetic pathogenesis of two patients from unrelated families with NPC. METHODS: DNA was extracted from the peripheral blood of the two patients and their families and from healthy individuals. Whole-exome sequencing followed by Sanger sequencing was performed to verify the mutations identified in their families. RESULTS: We identified four mutations in NPC1 in the two patients from different families: c.1290delC (p.F431Lfs*18)/c.2807G > A(p.G936D) in family A and c.3604_3605insA (p.I1202Nfs*56)/c.881 + 3A > G in family B from their parents. Bioinformatics analysis predicted these mutations to be deleterious, suggesting that mutations in exons are highly conservative. The patient in family A presented with a developmental delay that was different from the typical symptoms of developmental regression in family B. CONCLUSION: Our study identified three novel mutations and one known mutation in NPC1 and evaluated their pathogenicity, enriching the NPC1 mutation and phenotype spectrum and providing a new basis for the genetic and prenatal diagnosis of this disease.

Early life exposure to triclosan from antimicrobial daily necessities may increase the potential risk of autism spectrum disorder: A multicenter study in China.

BACKGROUND: Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders with unclear etiologies. Our recent work indicated that maternal exposure to triclosan (TCS) significantly increased the autistic-like behavior in rats, possibly through disrupting neuronal retinoic acid signaling. Although environmental endocrine disruptors (EEDs) have been associated with autism in humans, the relationship between TCS, one of the EEDs found in antibacterial daily necessities, and autism has received little attention. OBJECTIVE: The aims of this multicenter study were to evaluate TCS concentrations in typically developing (TD) children and ASD children, and to determine the relationship between TCS levels and the core symptoms of ASD children. METHODS: A total of 1345 children with ASD and 1183 TD children were enrolled from 13 cities in China. Ages ranged between 2 and 7 years. A questionnaire was used to investigate the maternal use of antibacterial daily necessities (UADN) during pregnancy. The core symptoms of ASD were evaluated using the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Response Scale (SRS), and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). The TCS concentration was measured using LC-MS/MS. RESULTS: Maternal UADN during pregnancy may be an unrecognized potential environmental risk factor for ASD (OR=1.267, P = 0.023). Maternal UADN during pregnancy strongly correlated with TCS levels in the offspring (Adjusted ß = 0.277, P < 0.001). TCS concentration was higher in ASD children (P = 0.005), and positively correlated with ABC (Sensory subscales: P = 0.03; Social self-help subscales: P = 0.011) and SRS scale scores (Social awareness subscales: P = 0.045; Social communication subscales: P = 0.001; Autism behavior mannerisms subscales: P = 0.006; SRS total score: P = 0.003) in ASD children. This association was more pronounced in boys than in girls. CONCLUSION: To our knowledge, this is the first case-control study to examine the correlation between TCS and ASD. Our results suggest that maternal UADN during pregnancy may be a potential risk of ASD in offspring. Further detection of TCS levels showed that maternal UADN during pregnancy may be associated with excessive TCS exposure. In addition, the level of TCS in children with ASD is higher than TD children. The higher levels of TCS in children with ASD may be significantly associated with more pronounced core symptoms, and this association was more significant in male children with ASD.

Mutations in ASH1L confer susceptibility to Tourette syndrome.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by repetitive motor movements and vocal tics. The clinical manifestations of TS are complex and often overlap with other neuropsychiatric disorders. TS is highly heritable; however, the underlying genetic basis and molecular and neuronal mechanisms of TS remain largely unknown. We performed whole-exome sequencing of a hundred trios (probands and their parents) with detailed records of their clinical presentations and identified a risk gene, ASH1L, that was both de novo mutated and associated with TS based on a transmission disequilibrium test. As a replication, we performed follow-up targeted sequencing of ASH1L in additional 524 unrelated TS samples and replicated the association (P value = 0.001). The point mutations in ASH1L cause defects in its enzymatic activity. Therefore, we established a transgenic mouse line and performed an array of anatomical, behavioral, and functional assays to investigate ASH1L function. The Ash1l+/- mice manifested tic-like behaviors and compulsive behaviors that could be rescued by the tic-relieving drug haloperidol. We also found that Ash1l disruption leads to hyper-activation and elevated dopamine-releasing events in the dorsal striatum, all of which could explain the neural mechanisms for the behavioral abnormalities in mice. Taken together, our results provide compelling evidence that ASH1L is a TS risk gene.

Sleep problems in children with autism spectrum disorder: a multicenter survey.

BACKGROUND: High prevalence of sleep problems have been reported in children with Autism Spectrum Disorder (ASD). This study aims to investigate the sleep conditions of ASD children in China, and explore the relationship between the common sleep problems and core symptoms and developmental levels. METHODS: Using a cross-sectional design, we included 2 to 7-year-old children from 13 cities in China: 1310 with ASD and 1158 with typically-developing (TD) children. The neurodevelopmental level was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). ASD were diagnosed with DSM-5 and Child Autism Rating Scale (CARS). the Social Responsiveness Scale (SRS), the Autism Behavior Checklist (ABC) and the communication warning behavior sub-scale in CNBS-R2016 valued autism behaviors. The children' s sleep habits questionnaire (CSHQ) assessed sleep conditions. RESULTS: The prevalence of sleep disorders in ASD children was significantly higher than that in TD (67.4% vs. 51%, p < 0.01), and among them the four dimensions with the highest prevalence of sleep problems were bedtime resistance (25.6%), sleep anxiety (22.7%), sleep onset delay (17.9%) and daytime sleepiness (14.7%). ASD children with sleep onset delay or sleep anxiety had higher ABC, SRS scores and higher scores on communication warning behavior with sleep anxiety, with daytime sleepiness had higher ABC, SRS and CARS scores, and with bedtime resistance had higher SRS total scores. Differences in the neurodevelopmental level were not significant. CONCLUSION: Children with ASD have a higher prevalence of sleep problems. Bedtime resistance, anxiety, sleep onset delay and daytime sleepiness may be related to the core symptoms, but not be related to the developmental level in ASD children. In the clinic, sleep assessment should be included in the routine of ASD visits, and during the intervention, sleep hygiene education is as important as the treatment of biological factors. TRIAL REGISTRATION: The study was approved by the ethics committee of the Children's Hospital of Chongqing Medical University, Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194 ).

[Association between serum trace elements and core symptoms in children with autism spectrum disorder: a national multicenter survey].

OBJECTIVE: To study the association of serum levels of trace elements with core symptoms in children with autism spectrum disorder (ASD). METHODS: From September 2018 to September 2019, an investigation was performed for 1 020 children with ASD and 1 038 healthy children matched for age and sex in the outpatient service of grade A tertiary hospitals and special education institutions in 13 cities of China. Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood Autism Rating Scale (CARS) were used to assess the core symptoms of the children with ASD. The inductively coupled plasma mass spectrometry was used to measure serum levels of trace elements magnesium, iron, copper, and zinc. RESULTS: The children with ASD had significantly lower serum levels of magnesium, copper, and zinc than the healthy children (P < 0.05). The children with severe ASD had significantly lower serum levels of magnesium and zinc than those with mild-to-moderate ASD (P < 0.05). The results of partial correlation analysis showed that serum magnesium level was negatively correlated with the total score of ABC and the score of communication (r=-0.318 and -0.282 respectively; P 0.001), and serum zinc level was negatively correlated with the total score of ABC and the scores of communication and somatic movement (r=-0.221, -0.270, and -0.207 respectively; P < 0.001). CONCLUSIONS: The serum levels of magnesium and zinc may be associated with core symptoms in children with ASD, which requires further studies. The nutritional status of trace elements should be monitored for children with ASD in clinical practice.

MiR-204-5p Inhibits Transforming Growth Factor-ß1-Induced Proliferation and Extracellular Matrix Production of Airway Smooth Muscle Cells by Regulating Six1 in Asthma.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1)-in-duced proliferation of airway smooth muscle cells plays critical roles in the development of airway remodeling. Six1 (sine oculis homeobox homolog 1) has been demonstrated to be involved in airway inflammation and remodeling in asthmatic mice. OBJECTIVES: The aim of this work was to investigate the potential role of miR-204-5p in the proliferation and extracellular matrix (ECM) production of airway smooth muscle cells in asthma. METHODS: Real-time PCR was used to measure the expression of miR-204-5p in asthmatic airway smooth muscle cells. Cell viability and apoptosis were detected to evaluate the effect of miR-204-5p on airway smooth muscle cells. Dual-luciferase reporter experiments were applied to identify the target genes of miR-204-5p. RESULTS: MiR-204-5p was downregulated notably in asthmatic airway smooth muscle cells as well as cells stimulated with TGF-ß1. Overexpression of miR-204-5p markedly suppressed the TGF-ß1-induced proliferation of airway smooth muscle cells and the deposition of ECM, whereas the inhibition of miR-204-5p significantly enhanced the proliferation of airway smooth muscle cells and upregulated the level of fibronectin and collagen III. Furthermore, subsequent analyses demonstrated that Six1 was a direct target of miR-204-5p, and Western blot further indicated that miR-204-5p negatively regulated the expression of Six1. Most importantly, the restoration of Six1 expression reversed the inhibitory effect of miR-204-5p on TGF-ß1-induced proliferation and ECM production. CONCLUSIONS: MiR-204-5p inhibits TGF-ß1-in-duced proliferation and ECM production of airway smooth muscle cells by regulating Six1, identifying a potential therapeutic target for preventing airway remodeling in asthma.

Correlation between oxidative stress and NF-κB signaling pathway in the obesity-asthma mice.

In this study, a mice model of obesity-asthma was established. We investigated the correlation between oxidative stress and NF-κB signaling pathway in the lung tissues, together with the effects of acetylcysteine. The animals were fed on a high-fat diet, and then ovalbumin (OVA) sensitization was utilized to establish the obesity-asthma model. N-acetylcysteine was used to treat asthma, animals treated with budesonide served as control. The malondialdehyde (MDA) in the lung tissues was determined, together with the activity of glutathione (GSH). EMAS assay was utilized to measure the nuclear factor-κB-P65 (NF-κB-P65) in lung tissues. Western blot analysis was performed to determine the expression of inhibitor kappa B-α (IκB-α) and inhibitor kappa B kinase-ß (IKK-ß). The MDA in the asthma groups showed significantly elevation (P < 0.01), and the GSH showed significant decrease (P < 0.01), especially in the obesity-asthma group. The efficiency of N-acetylcysteine was superior to that of the budesonide in the decline of MDA and elevation of GSH (P < 0.01). In both asthma groups, the expression of IKK-ß and transcription of NF-κB-P65 in the lung tissues showed significant elevation (P < 0.01), and IκB-α showed significant decline (P < 0.01), especially in the obesity-asthma group. There was decline of IKK-ß and NF-κB-P65 and elevation of IκB-α in the N-acetylcysteine group, which was even significantly in the Budesonide group (P < 0.01). There was a positive correlation between MDA and NF-κB activation in the lung tissues in all the asthma groups and treatment groups (P < 0.05). Obesity-asthma mice showed higher oxidative stress and activation of NF-κB compared with that of the asthma mice. There was a positive correlation between MDA and NF-κB activation in the lung tissues in the asthma groups. N-acetylcysteine was more effective in reducing the oxidative stress compared to the budesonide.

[Analysis of clinical features and genetic variants in an infant with Bloom syndrome].

OBJECTIVE: To analyze the clinical features and genetic variants in a 13-month-old child with Bloom syndrome. METHODS: Clinical data of the child was collected. Genetic variants were detected by high-throughput sequencing and Sanger sequencing. RESULTS: The child was born at full term but was small for gestational age. His clinical features included loss of appetite, severe growth retardation, microcephaly, and small mandible. Genetic testing found that he had carried compound heterozygous c.1068+3A>C and c.1069-1G>C variants of the BLM gene, both of which were unreported previously. CONCLUSION: Bloom syndrome is mainly characterized by severe growth retardation in infancy. The novel variants have expanded the variant spectrum of the BLM gene.

MiR-448-5p inhibits TGF-ß1-induced epithelial-mesenchymal transition and pulmonary fibrosis by targeting Six1 in asthma.

MicroRNAs (miRNAs) are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation. The aim of this study was to explore how miR-448-5p affects airway remodeling and transforming growth factor-ß1 (TGF-ß1)-stimulated epithelial-mesenchymal transition (EMT) by targeting Sine oculis homeobox homolog 1 (Six1) in asthma. Asthmatic mice models with airway remodeling were induced with ovalbumin solution. MiRNA expression was evaluated using quantitative real-time polymerase chain reaction. Transfection studies of bronchial epithelial cells were performed to determine the target genes. A luciferase reporter assay system was applied to identify whether Six1 is a target gene of miR-448-5p. In the current study, we found that miR-448-5p was dramatically decreased in lung tissues of asthmatic mice and TGF-ß1-stimulated bronchial epithelial cells. In addition, the decreased level of miR-448-5p was closely associated with the increased expression of Six1. Overexpression of miR-448-5p decreased Six1 expression and, in turn, suppressed TGF-ß1-mediated EMT and fibrosis. Next, we predicted that Six1 was a potential target gene of miR-448-5p and demonstrated that miR-448-5p could directly target Six1. An SiRNA targeting Six1 was sufficient to suppress TGF-ß1-induced EMT and fibrosis in 16HBE cells. Furthermore, the overexpression of Six1 partially reversed the protective effect of miR-448-5p on TGF-ß1-mediated EMT and fibrosis in bronchial epithelial cells. Taken together, the miR-448-5p/TGF-ß1/Six1 link may play roles in the progression of EMT and pulmonary fibrosis in asthma.

[Association of exposure to polycyclic aromatic hydrocarbons during pregnancy with autism spectrum disorder-related behaviors in toddlers: a birth cohort study].

OBJECTIVE: To study the association of exposure to polycyclic aromatic hydrocarbons (PAH) during pregnancy and autism spectrum disorder (ASD)-related behaviors in toddlers. METHODS: A total of 348 toddlers who had accepted the measurement of PAH-DNA adduct in umbilical cord blood and evaluation of behavior problems at the age of 36 months were enrolled in this birth cohort study. Child Behavior Checklist (CBCL) and Autism Behavior Checklist (ABC) were used to evaluate behavior problems at the age of 36 months. The correlation of the concentration of PAH-DNA adduct in umbilical cord blood with CBCL and ABC scores at the age of 36 months were analyzed. RESULTS: The detection rate of PAH-DNA adduct in umbilical cord blood was 52.3%, and the median concentration was 0.68 ng/mL. The median total scores of CBCL and ABC scales were 23 and 8 respectively. In children aged 36 months, the concentration of PAH-DNA adduct was positively correlated with the score of social withdrawal in the CBCL scale (rs=0.205, P<0.05), the total score of the ABC scale (rs=0.412, P<0.05), and the self-care score of the ABC scale (rs=0.355, P<0.05). The concentration of PAH-DNA adduct was closely associated with the total score of the ABC scale in children aged 36 months (ß=0.122, P<0.05). CONCLUSIONS: PAH exposure during pregnancy may be a risk factor for ASD-related behaviors in toddlers. Effective reduction of PAH exposure during pregnancy and detection of PAH-DNA adduct in neonatal umbilical cord blood are of vital importance for early prevention, screening and intervention of ASD.

Variable number tandem repeats in dopamine receptor D4 in Tourette's syndrome.

BACKGROUND: We attempted to clarify the association between dopamine receptor D4 (DRD4) 48-bp variable number of tandem repeats (VNTR) polymorphism and Tourette's syndrome. METHODS: The DRD4 48-bp VNTR polymorphism was genotyped in 291 Tourette's syndrome patients (including 218 trios) and 405 controls. Chi-square and transmission disequilibrium test analysis were used to compare genetic distributions. We retrieved related studies in a meta-analysis to clarify the role of 2-repeat and 4-repeat alleles in the pathogenesis. RESULTS: Obvious genotype and allele distribution differences were observed between patients and healthy controls for both 2-repeat and 4-repeat alleles. This was verified using transmission disequilibrium test analysis. Meta-analysis showed strong associations in both the total population and the Asian population. CONCLUSIONS: The DRD4 48-bp VNTR polymorphism appears to be associated with Tourette's syndrome, with the 2-repeat allele performing a protective role and the 4-repeat allele a nonprotective role in the genesis of the disease.

[Association of serotonin transporter linked polymorphic region 44 bp variable number of tandem repeat polymorphism with Tourette syndrome].

OBJECTIVE: To assess the association between the serotonin transporter linked polymorphic region (5-HTTLPR) 44 bp variable number of tandem repeat (VNTR) polymorphism and Tourette syndrome (TS) in ethnic Han Chinese trios. METHODS: A total of 252 TS trios (patients and their parents) were recruited. Genetic contribution of the 5-HTTLPR 44 bp VNTR polymorphism was evaluated by genotyping, haplotype relative risk (HRR) analysis and transmission disequilibrium test (TDT) statistics. To enhance the efficiency of the test, haplotype-based HRR (HHRR) was also performed. RESULTS: The TDT, HRR and HHRR analyses have revealed a significant association of the 5-HTTLPR 44 bp VNTR polymorphism with TS, and provided a strong evidence for an over-transmission of L allele from parents to the affected children (TDT: χ² = 6.680, df= 1, P= 0.012; HRR: χ² = 9.345, P= 0.002, OR= 1.739, 95% CI for 1.218-2.483). For 204 male and 48 female TS trios, TDT and HRR were analyzed separately. The results showed a significant association between 5-HTTLPR and male TS (for males. TDT: χ² = 4.643, df= 1, P= 0.038; for females, TDT: χ² = 2.189, df= 1, P= 0.188). CONCLUSION: 5-HTTLPR may be the susceptibility gene for male TS patients among the Chinese Han population. However, the results need to be replicated in datasets collected from different populations.

[Comparative analysis of four kinds of vitamin B of milk of lactating mothers and maternal and infant nutritional status in Chinese urban and rural areas].

OBJECTIVE: To understand the nutritional level of lactating mothers and infant by detecting the content of the vitamin B1, vitamin B2, vitamin B6, nicotinic of milk of urban and rural areas and to provide the basis for improving vitamin nutritional status of lactating women and their babies. METHODS: Totally 92 pairs of breastfeeding healthy mothers and their children in Shandong Province were selected. 34 pairs were in a urban area and 58 pairs were in a rural area. Collect the milk of selected lactating mothers and the urine of the lactating mothers and their children. Detect the content of vitamin B1, vitamin B2, vitamin B6, nicotinic of milk of lactating mothers and the content of vitamin B1, vitamin B2, nicotinic of urine of lactating mothers and their children. RESULTS: The content of vitamin B2, vitamin B6 and niacin of milk of urban lactating mothers were significantly higher than that of rural lactating mothers. The results of detection showed the vitamin B2 of milk of urban lactating mothers was 149.77 microg/100 g, which was significantly higher than that of rural women in 85.09 microg/100 g (P < 0.05). Vitamin B6 and niacin contents were 15.29 microg/100 g, 40.83 microg/100 g, which were also higher than that in rural lactating milk (6.69 microg/100 g and 24.48 microg/100 g) (All values P < 0.05). However, vitamin B1 of milk of urban and rural lactating mothers were 5.54 microg/100 g and 4.80 microg/100 g respectively, which had no significant difference. Urine analysis showed vitamin B2 and niacin of urban mothers and children were significantly higher than that in rural area (P < 0.05). But the level of vitamin B1 of rural children was higher than that of urban children (P < 0.05). There was no significant difference in the vitamin B1 between urban and rural mothers. The insufficient percentages of vitamin B1, vitamin B2. niacin in urban mothers was 23.5%, 32.3% and 17.6%, and that in rural mothers were 29.3%, 82.8% and 53.4%. The deficiency percentage of vitamin B1, vitamin B2, niacin in urban children were 2.9%, 2.9% and 11.8%, and that in rural children were 5.1%, 51.8% and 25.8%. CONCLUSION: The insufficient percentage of vitamin B1 in urban and rural mothers was high and the content of vitamin B1 of milk was low. While the insufficient percentage of vitamin B2, niacin of rural lactating mothers and children were higher than that of urban mothers and children.

Alterations in the gut microbiota of toddlers with cow milk protein allergy treated with a partially hydrolyzed formula containing synbiotics: A nonrandomized controlled interventional study.

Formulas containing intact cow milk protein are appropriate alternatives when human milk (HM) is not feasible. However, for babies with a physician-diagnosed cow milk protein allergy (CMPA), hydrolyzed formulas are needed. We conducted a 3-month, open-label, nonrandomized concurrent controlled trial (ChiCTR2100046909) between June 2021 and October 2022 in Qingdao City, China. In this study, CMPA toddlers were fed with a partially hydrolyzed formula containing synbiotics (pHF, n = 43) and compared with healthy toddlers fed a regular intact protein formula (IF, n = 45) or HM (n = 21). The primary endpoint was weight gain; the secondary endpoints were changes in body length and head circumference of both CMPA and healthy toddlers after 3-month feeding; and the exploratory outcomes were changes in gut microbiota composition. After 3 months, there were no significant group differences for length-for-age, weight-for-age, or head circumference-for-age Z scores. In the gut microbiota, pHF feeding increased its richness and diversity, similar to those of IF-fed and HM-fed healthy toddlers. Compared with healthy toddlers, the toddlers with CMPA showed an increased abundance of phylum Bacteroidota, Firmicutes, class Clostridia, and Bacteroidia, and a decreased abundance of class Negativicutes, while pHF feeding partly eliminated these original differences. Moreover, pHF feeding increased the abundance of short-chain fatty acid producers. Our data suggested that this pHF partly simulated the beneficial effects of HM and shifted the gut microbiota of toddlers with CMPA toward that of healthy individuals. In conclusion, this synbiotic-containing pHF might be an appropriate alternative for toddlers with CMPA.

Predicting autism spectrum disorder using maternal risk factors: A multi-center machine learning study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex environmental etiology involving maternal risk factors, which have been combined with machine learning to predict ASD. However, limited studies have considered the factors throughout preconception, perinatal, and postnatal periods, and even fewer have been conducted in multi-center. In this study, five predictive models were developed using 57 maternal risk factors from a cohort across ten cities (ASD:1232, typically developing[TD]: 1090). The extreme gradient boosting model performed best, achieving an accuracy of 66.2 % on the external cohort from three cities (ASD:266, TD:353). The most important risk factors were identified as unstable emotions and lack of multivitamin supplementation using Shapley values. ASD risk scores were calculated based on predicted probabilities from the optimal model and divided into low, medium, and high-risk groups. The logistic analysis indicated that the high-risk group had a significantly increased risk of ASD compared to the low-risk group. Our study demonstrated the potential of machine learning models in predicting the risk for ASD based on maternal factors. The developed model provided insights into the maternal emotion and nutrition factors associated with ASD and highlighted the potential clinical applicability of the developed model in identifying high-risk populations.

[Family-based association study of a variable number of tandem repeat polymorphism of DAT1 gene with Tourette syndrome in a Chinese Han population].

OBJECTIVE: To assess the association of a 40 bp variable number of tandem repeat (VNTR) polymorphism within 3 untranslated region of dopamine transporter gene (DAT1) with Tourette syndrome (TS) in a Chinese Han population. METHODS: A total of 160 TS patients and their parents were recruited. The VNTR polymorphism was detected with polymerase chain reaction-VNTR analysis, and its association with TS and its subtypes were assessed through a family-based association study comprising transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analysis. RESULTS: The repeat numbers at the DAT1 40 bp locus were 11, 10, 9, 7.5 and 7 among the patients and their parents, with the most common type being a 10-repeat allele. No significant association was detected between the polymorphism and TS (TDT: X ² = 0.472, df = 1, P = 0.583; HRR: X ² = 0.313, P = 0.576, OR = 0.855, 95%CI: 0.493-1.481). CONCLUSION: Our data suggested that the VNTR polymorphism of DAT1 gene is not associated with susceptibility to TS in Chinese Han population. However, our results are to be validated in larger sets of patients collected from other populations.

[Investigation of vitamin B1, vitamin B2 and niacin levels among children aged 0-3 years old in Chinese urban and rural areas].

OBJECTIVE: To study the nutritional status and differences in vitamin B1, vitamin B2, and niacin of the urban/rural infants in Shandong Province, and to provide scientific basis for infants nutrition interventions. METHODS: 106 urban infants and 290 rural infants were selected from a city in Shandong Province. Forty milliliter urinary was collected from each one, which was adjusted to pH 4-5 with concentrated hydrochloric acid immediately. The concentration of thiamine, riboflavin and niacin in the urine was detected by fluorescence method. RESULTS: The insufficient percentages of vitamin B, vitamin B2 and niacin in urban infants were 1.9%, 8.0% and 9.1%, and that in rural infants were 4.5%, 56.7% and 27.1%. The median concentrations of vitamin B1 in urban and rural infants were 495.00 and 420.56 microg/g respectively, in which the 12-month and 24-month groups in urban were higher than that in rural (P<0.05). The medians of vitamin B2 content in urban and rural infants were 303.07 and 70.88 microg/g, and the content of vitamin B2 in urban infants was higher than that in rural infants in each group (P<0.05). The median concentrations of niacin content in urban and rural infants were 6.31 and 4.22 microg/g, and the niacin content of 6month-, 12 month-, 18 month- and 24 month- groups in urban infants were higher than that in rural infants (P<0.05). CONCLUSION: There were significant differences in vitamin B1, B2 and niacin content of infants between urban and rural areas, and the nutriture of urban infants was better than the rural infants. More improvement measures should be given to infants in rural areas for the high proportion of vitamin B, and niacin deficiency.

[Retracted] Inhibition airway remodeling and transforming growth factor­ß1/Smad signaling pathway by astragalus extract in asthmatic mice.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the P­smad2 western blotting data shown in Fig. 7 were strikingly similar to data appearing in different form (namely, the bands appeared in the reverse orientation) in Fig. 4A in another article [Lv Z­D, Na D, Liu F­N, Du Z­M, Sun Z, Li Z, Ma X­Y, Wang Z­N and Xu H­M: Induction of gastric cancer cell adhesion through transforming growth factor­beta1­mediated peritoneal fibrosis. J Exp Clin Cancer Res 29: 139, 2010], which was written by mostly different authors at different research institutes (the author Zheng­Hai Qu did appear as an author on both papers). Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, and due to a lack of overall confidence in the presented data, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 29: 564­568, 2012; DOI: 10.3892/ijmm.2011.868].