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Objective To investigate the incidence of neonatal asphyxia and possible contributing factors for the development of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture, China. Methods A total of 16 hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture were selected as research centers. A retrospective analysis was performed for the clinical data of 22294 live births in these 16 hospitals from January to December, 2016 to investigate the incidence rate of neonatal asphyxia and possible contributing factors for the development of severe asphyxia. Results Of the 22 294 neonates born alive, 733 (3.29%) were diagnosed with neonatal asphyxia, among whom 627 had mild asphyxia and 106 had severe asphyxia. The neonates with low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight had a higher incidence of severe asphyxia (P < 0.05).Conclusions The incidence rate of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture is higher. Low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight may be related to the development of severe neonatal asphyxia.

Objective To investigate the use of antibiotics in children with community-acquired pneumonia (CAP) in multiple regions of China, and to provide a reference for CAP standard treatment and rational antibiotic use in children. Methods The medical data of 1383 children with CAP who were hospitalized in the department of pediatrics in 10 grade A tertiary hospitals from 9 cities between April 14, 2014 and January 1, 2016 were reviewed, to analyze the status of antibiotic use in hospitalized children in North China, Northeast China, East China, and South China. Results The overall rate of antibiotic use in children with CAP was 89.08%, with 88.7% in North China, 95.5% in Northeast China, 83.3% in East China, and 86.6% in South China. The main types of antibiotics used were cephalosporins, macrolides, compound preparations of β-lactam antibiotics, polyphosphoric broad-spectrum antibiotics and other β-lactam antibiotics. The selection of antibiotics was generally rational, but antibiotics were still used in some patients with viral infection alone or a combined use of ≥ 2 kinds of antibiotics were noted in some patients with infection caused by one kind of pathogen. Irrational antibiotic use was observed in 131 children (10.63%). Conclusions There are high rates of antibiotic use and irrational use of antibiotics among children with CAP. Standard management of antibiotic use in children with CAP should be strengthened.

Objective To investigate the prevalence of Bordetella pertussis infection in children with chronic cough and its clinical features. Methods A total of 106 children who were treated at the outpatient service or hospitalized from January 1, 2016 to May 31, 2017 were enrolled. Their nasopharyngeal swabs and venous blood samples were collected for Bordetella pertussis culture, multiple PCR and serum anti-pertussis toxin antibody detection. According to these results, the children were divided into pertussis group with 26 children and control group with 80 children, and clinical features were analyzed for both groups. E-test stripes were used to determine the sensitivity of Bordetella pertussis strains to erythromycin, azithromycin, doxycycline, levofloxacin, sulfamethoxazole/trimethoprim and amoxicillin. Results Of the 106 children with chronic cough, 26 (24.5%) were found to have Bordetella pertussis infection. There were no significant differences in the incidence rates of typical symptoms of pertussis between the pertussis and control groups (P > 0.05). E-test showed that erythromycin and azithromycin had a minimal inhibitory concentration (MIC) of > 256 mg/L against five Bordetella pertussis strains, while amoxicillin had an MIC of 0.5-1 mg/L. Conclusions The presence of Bordetella pertussis infection in children with chronic cough should be taken seriously by clinicians, and children with chronic cough and Bordetella pertussis infection may not have the typical symptoms of pertussis and are mainly manifested as chronic cough. Amoxicillin may be an alternative drug for macrolide-resistant Bordetella pertussis infection.

Objective To investigate the complications and clinical outcome of children with acute myeloid leukemia (AML) undergoing mitoxantrone-cytarabine-etoposide (MAE) induction therapy. Methods A total of 170 children with AML were given MAE induction therapy, and the complications and remission rate were analyzed after treatment. Results The male/female ratio was 1.33:1 and the mean age was 7.4 years (range 1-15 years). Leukocyte count at diagnosis was 29.52×10⁹/L[range (0.77-351)×10⁹/L]. Of all children, 2 had M0-AML, 24 had M2-AML, 2 had M4-AML, 48 had M5-AML, 3 had M6-AML, 7 had M7-AML, 69 had AML with t(8;21)(q22;q22), and 15 had AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22). The most common complication was infection (158/170, 92.9%). Among these 158 patients, 22 (13.9%) had agranulocytosis with pyrexia (with no definite focus of infection), and 136 (86.1%) had definite focus of infection (including bloodstream infection). Other complications included non-infectious diarrhea, bleeding, and drug-induced hepatitis. Treatment-related mortality was observed in 10 children, among whom 8 had severe infection, 1 had multiple organ failure, and 1 had respiratory failure. Remission rate was evaluated for 156 children and the results showed a complete remission rate of 85.3%, a partial remission rate of 4.5%, and a nonremission rate of 10.3%. Conclusions Induction therapy with the MAE regimen helps to achieve a good remission rate in children with AML after one course of treatment. Infection is the main complication and a major cause of treatmentrelated mortality.

Four children (two boys and two girls), aged from 3 years and 7 months to 5 years, had mild or moderate anemia, mild hepatosplenomegaly, jaundice (mainly an increase in indirect bilirubin), an increase in the percentages of reticulocytes and spherical erythrocytes in peripheral blood smear and an increase in erythrocyte osmotic brittleness. High-throughput sequencing found two novel mutations in the SLC4A1 gene, c.37G > A and c.340T > C, in case 1 and case 2 respectively, and these two mutations were predicted to be pathogenic by Mutation Taster. The Polyphen2 scores of these two mutations were 0.87 and 0.83 respectively, which suggested that these mutations were probably damaging. The SIFT scores of these two mutations were 0.008 and 0.09 respectively, suggesting that these mutations were probably damaging. No abnormality in this gene was found in their parents. Two reported heterozygous mutations in the ANK1 gene, c.830A > G and c.985G > C, were found in case 3 and case 4 respectively. Gene detection was not performed for the parents of case 3. The mother of case 4 was diagnosed with hereditary spherocytosis and had a heterozygous mutation of c.985G > C in the ANK1 gene. All four children were diagnosed with hereditary spherocytosis. Case 3 had a hemoglobin level of < 80 g/L and underwent splenectomy at the age of 5 years and 6 months, and regular postoperative reexamination showed a hemoglobin level of > 105 g/L. Hereditary spherocytosis is a hereditary hemolytic disease caused by abnormality in erythrocyte membrane protein, and gene detection helps to make a confirmed diagnosis.

Inflammatory bowel disease (IBD) is a chronic recurrent non-specific inflammatory disease in the intestinal tract. About 10%-56% of children with Crohn's disease and about 10% of children with ulcerative colitis have growth retardation. This study reports four adolescents with IBD and growth hormone deficiency who were diagnosed with Crohn's disease. There were three boys and one girl, with an age of 11.0-13.9 years and a disease duration of 11-85 months at diagnosis. The four patients had the involvement of the small intestine only, the colon only, both the small intestine and the upper gastrointestinal tract, and both the small intestine and the colon respectively. The pediatric Crohn's disease activity index ranged from 27.5 to 45 points. All four patients had a height-for-age Z-score (HAZ) of < -2, and the growth hormone provocative test suggested growth hormone deficiency. Of all four patients, two received recombinant human growth hormone combined with infliximab, one received infliximab only, and one received recombinant human growth hormone combined with mercaptopurine. All four patients had an improvement in HAZ after treatment.

Objective To investigate the association between suppressor of cytokine signaling (SOCS) hypomethylation and T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance in children with Henoch-Schönlein purpura (HSP) and the immune pathogenesis of HSP. Methods A total of 32 children in the acute stage of HSP who were hospitalized from May 2014 to January 2015 were enrolled as subjects, and 28 children who underwent physical examination were enrolled as normal control group. ELISA was used to measure the plasma level of interleukin-6 (IL-6). Flow cytometry was used to measure the percentages of CD4⁺ IL-17A⁺ T cells (Th17 cells) and CD4⁺CD25⁺ Treg cells (Treg cells) in peripheral blood and mean fluorescence intensity (MFI) for phosphorylated-STAT3 (pSTAT3) protein in CD4⁺ T cells. Quantitative real-time PCR was used to measure the mRNA expression of suppressor of cytokine signaling-1 (SOCS1) and suppressor of cytokine signaling-3 (SOCS3) in CD4⁺ T cells. High-resolution melting (HRM) was used to evaluate the methylation level of the CpG islands in SOCS1 exon 2 and the CpG islands of the potential bind sites for STAT3 in the 5'-untranslated region (5'-UTR) of SOCS3 in peripheral blood mononucleated cells. Results Compared with the normal control group, the HSP group had significant increases in plasma IL-6 concentration and MFI for pSTAT3 in CD4⁺ T cells, as well as a significant increase in the percentage of Th17 cells and a significant reduction in the percentage of Treg cells (P < 0.05). The HSP group had significantly higher mRNA expression of SOCS1 and SOCS3 in peripheral blood mononucleated cells than the normal control group (P < 0.05). In the HSP group, the mRNA expression of SOCS1 and SOCS3 was negatively correlated with Th17/Treg ratio (P < 0.05). The HSP group had hypomethylation of the CpG islands in SOCS1 exon 2 and the potential binding site for STAT3 in SOCS3 5'-UTR, while the normal control group had complete demethylation. Conclusions Low relative expression of SOCS1 and SOCS3 caused by hypomethylation may be a factor for Th17/Treg imbalance in children with HSP.

Objective To evaluate the clinical value of droplet digital PCR (ddPCR) in rapid and accurate diagnosis of invasive fungal infection (IFI) in neonates. Methods The highly conserved sequence of fungi 18S RNA was selected as the target sequence, and primers were designed to establish a ddPCR fungal detection system. Blood samples were collected from 83 neonates with high-risk factors for IFI and/or related clinical symptoms in the neonatal intensive care unit (NICU) of a hospital in Shenzhen, China. Blood culture and ddPCR were used for fungal detection. Results The ddPCR fungal detection system had a specificity of 100% and a sensitivity of 3.2 copies/μL, and had a good reproducibility. Among the 22 blood samples from neonates with a confirmed or clinical diagnosis of IFI, 19 were detected positive by ddPCR. Among the 61 blood samples from neonates who were suspected of IFI or had no IFI, 2 were detected positive by ddPCR. Conclusions The ddPCR technique can be used for the detection of neonatal IFI and is a promising tool for the screening and even diagnosis of neonatal IFI.

Objective To investigate the epidemiological characteristics, phenotype, genotype, and prognosis of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in the Chinese population. Methods A retrospective analysis was performed for the clinical data of the neonates who underwent screening with high-performance liquid chromatography-tandem mass spectrometry from January 2009 to June 2018 and were diagnosed with MCADD by gene detection. Results A total of 2674835 neonates underwent neonatal screening, among whom 12 were diagnosed with MCADD. Gene detection was performed for 10 neonates with MCADD and found 13 mutation types at 16 mutation sites of the ACADM gene, among which there were 7 reported mutations (p.T150Rfs^*4, p.M1V, p.R206C, p.R294T, p.G310R, p.M328V, and p.G362E), 5 novel mutations (p.N194D, p.A324P, p.N366S, c.118+3A > G, and c.387+1del G), and 1 exon 11 deletion; p.T150Rfs^*4 was the most common mutation (4/16). The detection rate of mutation sites in the ACADM gene was 80%. No phenotype-genotype correlation was observed. Dietary guidance and symptomatic treatment were given after confirmed diagnosis. No acute metabolic imbalance was observed within 4-82 months of follow-up. All neonates had good prognosis except one who had brain dysplasia. Conclusions MCADD is relatively rare in southern China, and p.T150Rfs^*4 is a common mutation in the Chinese population. Cases with positive screening results should be evaluated by octanoylcarnitine C8 value and gene detection.

Objective To study the clinical effect of maternal voice stimulation in alleviating procedural pain in neonates during heel blood collection. Methods A total of 72 neonates who were admitted to the neonate intensive care unit were randomly divided into an intervention group (n=35) and a control group (n=37). Heel blood collection was performed by the routine method in the control group. The intervention group listened to their mothers' voice from 1 minute before heel blood collection to the end of the procedure. Pain score, incidence of crying, and vital signs were recorded before and after heel blood collection. Results Compared with the control group, the heart rate was significantly reduced, the blood oxygen saturation significantly increased, the incidence of crying and the pain score were significantly reduced in the intervention group during the procedure of heel blood collection (P < 0.05). Conclusions Maternal voice stimulation helps to reduce procedural pain and maintain stable vital signs in neonates.

Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder resulting from biallelic mutations of ABCC2 gene, with long-term or intermittent conjugated hyperbilirubinemia being the main clinical manifestation. This paper aims to report the clinical features and ABCC2 genotypes of an infant with DJS. A 9.5-month-old male infant was referred to the hospital due to abnormal liver function discovered over 9 months. The major clinical presentation was prolonged jaundice since neonatal period. A series of biochemistry analysis revealed markedly elevated total bilirubin, conjugated bilirubin and total bile acids. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined etiology. Physical examination revealed jaundiced skin and sclera, and a palpable liver 3 cm below the right subcostal margin with medium texture. The spleen was not enlarged. Genetic analysis revealed a splice-site variant c.3988-2A > T and a nonsense variant c.3825C > G (p.Y1275X) in the ABCC2 gene of the infant, which were inherited from his mother and father respectively. The former had not been previously reported. Then ursodeoxycholic acid and phenobarbital were given orally. Half a month later, as a result, his jaundice disappeared and the biochemistry indices improved. However, the long-term outcome needs to be observed. Literature review revealed that neonates/infants with DJS presented with cholestatic jaundice soon after birth as the major clinical feature, and the ABCC2 variants exhibited marked heterogeneity.

GM1 gangliosidosis is an autosomal recessive disorder caused by galactosidase beta1 (GLB1) gene variants which affect the activity of β-galactosidase (GLB). GLB dysfunction causes abnormalities in the degradation of GM1 and its accumulation in lysosome. This article reports the clinical and genetic features of a child with GM1 gangliosidosis. The girl, aged 2 years and 5 months, was referred to the hospital due to motor developmental regression for more than one year. Physical examination showed binocular deflection and horizontal nystagmus, but no abnormality was found on fundoscopy. The girl had increased muscular tone of the extremities, limitation of motion of the elbow, knee, and ankle joints, and hyperactive patellar tendon reflex. Blood biochemical examination showed a significant increase in aspartate aminotransferase. The 24-hour electroencephalographic monitoring detected frequent seizure attacks and diffuse θ wave activity, especially in the right hemisphere. Head magnetic resonance imaging showed thinner white matter in the periventricular region and diffuse high T2WI signal with unclear boundary. Three-dimensional reconstruction of white matter fiber tracts by diffusion tensor imaging showed smaller and thinner white matter fiber tracts, especially in the right hemisphere. Genetic analysis showed that the girl had compound heterozygous mutations of c.446C > T (p.Ser149Phe) and c.101T > C (p.Ile34Thr) in the GLB1 gene from her parents, among which c.101T > C (p.Ile34Thr) had not been reported in the literatures. The girl was finally diagnosed with GM1 gangliosidosis. Her conditions were not improved after antiepileptic treatment and rehabilitation training for 2 months.

Objective To investigate the development of social skills in children with autism spectrum disorder (ASD) and related influencing factors. Methods A total of 889 children with ASD in 10 cities of China were enrolled as subjects. The Autism Social Skills Scale was used to assess their social skills. Results The children with ASD had a lower score of each factor than the theoretical median, with the lowest score for social communication and the highest score for self-regulation. There were significant differences in the total score of social skills and the scores of social cognition and social participation between the children with ASD in different age groups (P < 0.05). There were also significant differences in the total score of social skills and the scores of social orientation, social communication, social participation, and self-regulation between the ASD children with different language levels (P < 0.01). Conclusions Children with ASD have low social skills, and their social skills are associated with age and language level.

Objective To systematically review the effect of probiotic supplementation during pregnancy and infancy in preventing atopic dermatitis in children. Methods RevMan5.3 was used to perform a Meta analysis of randomized controlled trials on the effect of probiotic supplementation during pregnancy and infancy in preventing atopic dermatitis in children published between January 2008 and May 2018 across the world. A subgroup analysis was conducted according to the type of probiotics for intervention, follow-up time, time of probiotic supplementation, and study areas. Results A total of 22 articles were selected, with 3 280 cases in the intervention group and 3 281 cases in the control group. The results of pooled effect size showed that probiotic supplementation during pregnancy and/or infancy significantly reduced the incidence rate of atopic dermatitis (RR=0.81, 95% CI:0.70-0.93, P < 0.05). According to the subgroup analysis, the intervention with Lactobacillus and Bifidobacterium had a significant effect (RR=0.68, 95% CI:0.52-0.90, P < 0.05); probiotic supplementation during both pregnancy and infancy also had a significant effect (RR=0.77, 95% CI:0.66-0.90, P < 0.05); probiotic supplementation during pregnancy and/or infancy had a better effect in preventing atopic dermatitis in children aged ≤ 2 years than in those aged > 2 years (RR=0.74, 95% CI:0.61-0.90, P < 0.05); probiotic supplementation had a significant effect in Australia (RR=0.83, 95% CI:0.73-0.96, P < 0.05) and Europe/the United States (RR=0.74, 95% CI:0.61-0.91, P < 0.05). Heterogeneity was mainly due to follow-up time (I²=62.7%) and time of probiotic supplementation (I²=53.5%). Conclusions Probiotic supplementation during pregnancy and infancy helps to prevent atopic dermatitis in children, and mixed Lactobacillus-Bifidobacterium intervention has a better effect.

Objective To study the effect of glutamine-supplemented enteral nutrition in regulating the apoptosis of intestinal mucosal cells and promoting mucosal healing in young rats with inflammatory bowl disease (IBD). Methods A total of 80 male Sprague-Dawley rats aged 4-5 weeks were randomly divided into 4 groups:blank control, IBD model, short peptide, and short peptide+glutamine (n=20 each). The IBD model was prepared by a single colon perfusion of 3-nitrobenzene sulfonic acid. At 3 days after modeling, the rats in the short peptide group were fed with short peptide formula (100 mL/kg), and those in the short peptide+glutamine group were fed with short peptide formula (100 mL/kg) and glutamine (0.5 g/kg). The course of intervention was 1 week. General conditions were observed after the experiment and their intestinal mucosal tissue was obtained. Hematoxylin-eosin staining was used to observe the pathological change of the intestinal mucosa. RT-PCR was used to measure the expression of apoptosis-regulating genes (bax and bc1-2) and apoptotic signal transduction factors (Caspase-3 and Caspase-9) in the intestinal mucosa. Western blot was used to measure the expression of insulin-like growth factor-1 (IGF-1) in the colonic mucosa. Results The IBD model group had poorer general conditions than the other three groups (blank control, short peptide and short peptide+glutamine), and the short peptide+glutamine group had better general conditions than the IBD model and short peptide groups. The IBD model group had significantly higher mRNA expression of bax than the other three groups (P < 0.05). There was no significant difference in the mRNA expression of bcl-2, Caspase-3 and Caspase-9 among the 4 groups (P > 0.05). The short peptide group had a significantly higher level of IGF-1 than the short peptide+glutamine, blank control and IBD model groups (P < 0.05). Conclusions Glutamine-supplemented enteral nutrition can effectively improve the general nutritional status of young rats with IBD, but it is not better than exclusive enteral nutrition in inhibiting the apoptosis of colonic mucosal cells and stimulating the synthesis of IGF-1 in the intestinal mucosa.

The widespread use of mechanical ventilation technology has contributed to the successful treatment of many children with respiratory failure. At the same time, forced ventilation and changes in normal respiratory physiology and mechanics may lead to respiratory dysfunction and decreased airway clearance ability. Therefore, how to perform a comprehensive and accurate respiratory function assessment, conduct appropriate respiratory function rehabilitation, perform extubation as soon as possible, and shorten the duration of mechanical ventilation based on the children's own physiological characteristics, is a focus of the research on effective weaning from mechanical ventilation in children with severe conditions. This article reviews the advances in the respiratory function assessment and treatment methods in children undergoing invasive mechanical ventilation.