Objective:To explore the correlation between neurodevelopmental levels and core symptoms in children with autism spectrum disorder(ASD)at different developmental levels.Methods:A retrospective analysis was conducted on 346 children diagnosed with ASD for the first time at the Department of Child Developmental and Behavioral, Women and Children’s Hospital, School of Medicine, Xiamen University from January 2021 to October 2023. The developmental quotient (DQ) of ASD children was assessed using the 0-6 years old children's neurodevelopmental assessment. A total DQ score less than 70 was classified as the low-functioning ASD group( n=285)and total DQ score more than 70 was classified as high-functioning ASD group( n=61). The core symptoms of ASD children were evaluated using the autism behavior checklist (ABC) and childhood autism rating scale (CARS). The analysis focused on comparing the core symptoms among different developmental levels and examining the impact of developmental quotient in various areas on these core symptoms. SPSS 21.0 statistical software was used for t-test and multiple linear regression analysis. Results:(1)The total score of ABC((60.71±22.61) vs(53.23±24.18), t=2.316, P=0.021), sensory factor((7.96±5.18) vs(6.36±4.60), t=2.233, P=0.026), language factor((13.44±5.86) vs(10.46±5.52), t=3.641, P<0.001), the total score of CARS((34.59±5.18) vs(31.07±5.72), t=4.731, P<0.001), relationship to people((2.82±0.66) vs(2.57±0.67), t=2.604, P=0.01), imitation((3.01±0.76) vs(2.61±0.88), t=3.646, P<0.001), emotional response((2.33±0.77) vs(1.97±0.73), t=3.41, P<0.001), body((2.01±0.78) vs(1.77±0.72), t=2.249, P=0.025), taste-smell-touch response and use((1.52±0.70) vs(1.31±0.53), t=2.163, P=0.031), verbal communication((3.19±0.64) vs(2.90±0.70), t=3.141, P=0.002), non-verbal communication((2.68±0.62) vs(2.20±0.60), t=5.595, P<0.001), activity level((2.33±0.78) vs(2.10±0.83), t=2.108, P=0.036), level and consistency of intellectual response((2.14±0.76) vs(1.77±0.72), t=3.499, P=0.001), and general impressions of children ((2.36±0.59) vs(2.13±0.50), t=2.891, P=0.004)in the low-functioning ASD group were higher than those in the high-functioning ASD group.(2) Multiple stepwise linear regression analysis showed that children in high-functioning ASD group, language and fine motor domain DQ could negatively predict the total CARS score ( β=-0.383, -0.268; both P<0.05). Children in low-functioning ASD group, language and gross motor domains DQ could negatively predict the total CARS score( β=-0.233, -0.149, both P<0.01). Conclusions:The lower the development level, the more severe the core symptoms of ASD children. Fine motor and language ability have an impact on the core symptoms of ASD children with higher development level, while gross motor and language ability have an impact on the core symptoms of ASD children with low development level. In clinical practice, appropriate motor intervention plans can be formulated according to the development level of ASD children.

A 27-year-old male was admitted to the Xijing Hospital in August 2018 due to unprovoked severe thoracodynia with palpitations, shortness of breath and chest tightness. Computed tomography angiography showed a type A aortic dissection. Genetic testing based on next-generation sequencing for 15 genes associated with hereditary aortic diseases and Sanger sequencing validation revealed a heterozygous missense mutation c.998G>T (p.Gly333Val) in the COL3A1 gene. Sanger sequencing verification of family members confirmed that the mutation c.998G>T co-segregated with the patient′s phenotype in this family. That mutation was classified as "likely pathogenic" according to American College of Medical Genetics and Genomics standards and guidelines for genetic variant classification. Carriers of this mutation can be definitively diagnosed with "vascular Ehlers-Danlos syndrome". After the diagnosis was clarified, symptomatic treatment was given to the patient, but the disease progressed rapidly. The patient discontinued treatment and died shortly after being discharged. In this study, we found a new variant in the COL3A1 gene, expanding the mutation spectrum of this gene.

OBJECTIVE: To analyze the clinical phenotypes and genetic variants of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: A pedigree presented at the First Affiliated Hospital of Air Force Medical University on December 24,2021 was selected as the study subject. Activated partial thromboplastin time (APTT) and coagulation factor Ⅻ activity (FⅫ:C) were determine by a clotting method, and FⅫ antigen was detected with an ELISA assay. Following the extraction of genomic DNA, all exons and flanking regions of the F12 gene were subjected to Sanger sequencing. Clustalx-2.1-win, PROVEAN and Swiss-PDB Viewer software was used to analyze the conservation of amino acids at the variant sites, impact of of the variants on the amino acid substitutions and the protein structure. RESULTS: The APTT of the proband has prolonged to 70.2 s. Her FⅫ:C and FⅫ:Ag have decreased to 12% and 13%, respectively. DNA sequencing revealed that the proband has harbored c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) heterozygous compound missense variants in exons 5 and 13 of the F12 gene, respectively. Her father and sister were heterozygous carriers for the c.346G>A (p.Gly97Ser) variant, whilst her mother and brother were heterozygous for the c.1583C>A (p.Ser509Tyr) variant. CONCLUSION The c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) compound heterozygous variants of the F12 gene probably underlay the pathogenesis of hereditary coagulation FⅫ deficiency in this pedigree.
Humans ; Male ; Female ; Pedigree ; Factor XII/genetics* ; Mutation ; East Asian People ; Heterozygote ; Mothers ; Factor XII Deficiency/genetics*

BACKGROUND: Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease. METHODS: The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease. RESULTS: A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m³ increase of gestational exposure to PM_2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1^st-2^nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O₃ exposure during the 1^st week and SO₂ exposure during 6^th-7^th weeks in the first trimester, while no significant findings for other air pollutants. CONCLUSIONS This study highlighted that gestational exposure to PM_2.5, O₃, and SO₂ had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.
Infant ; Pregnancy ; Child ; Humans ; Female ; Air Pollutants/analysis* ; Case-Control Studies ; Prenatal Exposure Delayed Effects/epidemiology* ; Heart Defects, Congenital/etiology* ; China/epidemiology* ; Particulate Matter/adverse effects* ; Maternal Exposure/adverse effects*

Rhodotorula toruloides is a non-conventional red yeast that can synthesize various carotenoids and lipids. It can utilize a variety of cost-effective raw materials, tolerate and assimilate toxic inhibitors in lignocellulosic hydrolysate. At present, it is widely investigated for the production of microbial lipids, terpenes, high-value enzymes, sugar alcohols and polyketides. Given its broad industrial application prospects, researchers have carried out multi-dimensional theoretical and technological exploration, including research on genomics, transcriptomics, proteomics and genetic operation platform. Here we review the recent progress in metabolic engineering and natural product synthesis of R. toruloides, and prospect the challenges and possible solutions in the construction of R. toruloides cell factory.
Gene Editing ; Metabolic Engineering ; Rhodotorula/metabolism* ; Lipids

Objective To investigate the effect of enteral nutritional support beginning at different time on aspiration events and immune function in the early post-traumatic (within 14 days) period in patients with severe traumatic brain injury.Methods From June, 2018, to February, 2021, 75 patients with acute traumatic brain injury admitted in the Department of Neurosurgery of the Second People's Hospital of Lianyungang were randomly divided into early feeding group (24 to 48 hours, n=35) and delayed feeding group (48 to 120 hours, n=40). The 14-day reflux rate, aspiration rate, incidence of aspiration pneumonia, immune indexes and complications were compared between two groups.Results There was no significant difference in the reflux rate, aspiration rate and the incidence of aspiration pneumonia between the two groups (P > 0.05). The levels of IgG, IgA, and complements C3 and C4 were significantly higher in the early feeding group than in the delayed feeding group (|t| > 1.720, P<0.001). The incidence of non-aspiratory lung infections was significantly lower in the early feeding group than in the delayed feeding group (χ2=4.728, P<0.05).Conclusion Initiating enteral nutrition within 24 to 48 hours after injury may preserve immune function and reduce the incidence of non-aspiratory lung infections in patients with severe traumatic brain injury.

OBJECTIVE: To analyze the clinical phenotype and genetic basis of a consanguineous pedigree affected with hereditary coagulation factor XII (FXII) deficiency. METHODS: Following extraction of genomic DNA, all exons and flanking regions of F12 gene were subjected to PCR amplification and Sanger sequencing. ClustalX-2.1-win and MutationTaster software was used to analyze the conservation and impact of the variants on protein function. RESULTS: DNA sequencing showed that the proband carried a homozygous g.6753-6755delACA deletion (p.252delAsn) in exon 9 of the F12 gene, for which her father, mother and brother were heterozygous carriers. The same deletion was not found in her sister. CONCLUSION The homozygous p.252delAsn deletion probably underlies the hereditary FXII deficiency in this pedigree.

Objective:To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM).Methods:The efficacy and adverse events (AEs) of daratumumab based regimens were retrospectively analyzed in 37 patients with RRMM from Peking University People′s Hospital, Beijing Hospital and Fu Xing Hospital affiliated to Capital Medical University in China. The deadline for inclusion was December, 2019.Results:Among the 37 patients, 35 patients were available for response evaluation. The overall response rate (ORR) was 68.6%, which was better in patients receiving 16 mg/kg daratumumab than in those with fixed doses of 800 mg daratumumab [ORR: 78.3%(18/23) vs. 40.0%(4/10)]. The percentage of infusion related reactions of daratumumab was 27.0%(10/37). The most common hematological AEs were lymphocytopenia and thrombocytopenia, with the incidences of grade 3 or more severe 59.5%(22/37) and 43.2%(16/37) respectively. Pulmonary infections(37.8%, 14/37) were the most common non-hematological AEs. One patient with positive hepatitis B surface antigen (HBsAg) and two patients dependent on dialysis were safely treated with daratumumab.Conclusion:Daratumumab is highly effective in relapsed and refractory multiple myeloma. Adverse reactions are mild and well tolerable.

Objective: To investigate whether rapid weight gain in the first year of life was associated with incidence of overweight and higher blood pressure in small for gestational age (SGA) and appropriate for gestational age (AGA) infants at preschool age. Methods: From March 1, 2017 to June 30, 2018, a total of 12 150 children aged six years from 50 municipal kindergartens in Tianjin were enrolled in a cross-sectional survey. Their body weight, height and blood pressure were measured. Body length and weight at birth and one year of age were retrospectively collected. Rapid catch-up growth was defined as the difference of weight-for-height Z-score between one year old and at birth >0.67. The relationship between rapid growth with overweight and blood pressure in SGA and AGA infants at preschool age were analyzed using t test, analysis of variance and Chi-square test. Results: At the age of six, children with rapid growth had a higher rate of overweight [28.6% (2 095/7 328) vs 17.5% (842/4 822), t=196.457, P<0.001], and higher systolic blood pressure [(99.4±10.0) vs (98.4±10.1) mmHg (1 mmHg=0.133 kPa), t=29.260, P<0.001] and diastolic blood pressure [(60.0±7.7) vs (59.4±7.8) mmHg, t=16.079, P<0.001] compared with children without rapid growth. SGA children with rapid growth had higher body weight [(21.5±4.4) vs (19.2±3.7) kg, t=3.747, P<0.001], height [(117.4±5.5) vs (114.8±5.4) cm, t=3.557, P<0.001] and systolic blood pressure [(98.4±9.9) vs (95.6±11.2) mmHg, t=2.080, P=0.038] compared with those without. Comparing to AGA children, SGA children had lower overweight rate [17.5% (144/824) vs 24.7% (2 793/11 326), t=21.630, P<0.001] and systolic blood pressure [(98.2±10.0) vs (99.0±10.1) mmHg, t=2.431, P=0.015]. Among the AGA children with rapid growth, 29.8% (1 958/6 564) were overweight. Conclusions Rapid growth in infancy is associated with overweight and higher systolic blood pressure at preschool age. A proper weight gain should be emphasized for both SGA and AGA infants.

Objective: To explore the value of plasma cell-free DNA (cfDNA) in the assessment of inflammatory bowel disease (IBD) activity. Methods: From July 2014 to June 2017, 145 IBD patients from the First Affiliated Hospital of Fujian Medical University were selected. The plasma content of cfDNA was detected by picogreen-based fluorescent quantitative method. At the same period, 37 healthy individuals were enrolled as control group. The correlation between cfDNA content and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IBD activity was analyzed. The diagnostic capability of cfDNA in IBD activity was assessed by the receiver operating characteristic (ROC) curve. T-test was performed for comparison between two independent samples, and Pearson correlation coefficient test was used for correlation analysis between two variants. Results: The content of plasma cfDNA of patients with Crohn′s disease (CD) and patients with ulcerative colitis (UC) were (29.17±2.07) μg/L and (26.86±1.97) μg/L, respectively; which were both higher than those of healthy control group (21.10±1.02) μg/L, and the differences were statistically significant (t=2.609 and 2.082, both P<0.05). Moreover, the content of cfDNA of patients with active CD or UC were (35.72±3.26) μg/L and (32.37±3.42) μg/L, respectively, which were both higher than those of patients with CD or UC in remission ((21.12±1.43) μg/L and (20.82±1.02) μg/L), and the differences were statistically significant (t=3.806 and 3.116, both P<0.01). The cfDNA content of CD patients was positively correlated with CRP, ESR and disease activity (r=0.555, 0.393 and 0.400, all P<0.01). The cfDNA content of UC patients was also positively correlated with CRP, ESR and disease activity (r=0.640, 0.421 and 0.360, all P<0.01). The diagnostic capability of the combination of CRP and ESR was the highest in CD diagnosis, with the area under curve (AUC) value being 0.841, and the sensitivity and specificity being 81.4% and 74.3%, respectively. The diagnostic capability of the combination of cfDNA, CRP and ESR was the highest in UC diagnosis, with the AUC value being 0.851, and the sensitivity and specificity being 74.3% and 96.9%, respectively. Conclusions Increased cfDNA levels in IBD patients are correlated with IBD activity. Detection of cfDNA is helpful in the identification of active IBD, and the combination of ESR and CRP can improve the diagnostic efficiency of UC.