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    CLINICAL RESEARCH
  • ● CLINICAL RESEARCH
    BA Rui-Hua, MAO Jian
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    Objective To investigate the correlation between magnetic resonance imaging (MRI) score and clinical grading in neonatal hypoxic-ischemic encephalopathy (HIE).Methods Clinical grading was performed for 61 neonates with HIE according to the HIE clinical grading standard. The modified MRI scoring system was used to determine the injury scores on different MRI sequences. The correlation between HIE imaging score and clinical severity was analyzed.Results The MRI score in neonates with moderate HIE was significantly lower than that in those with severe HIE (P < 0.01). Neonates aged 0-7 days had the highest correlation coefficient between diffusion weighted imaging (DWI) score and total MRI score (r > 0.9), and neonates aged >7 days had the highest correlation coefficient between T1-weighted imaging score and total MRI score (r=0.963). Brain MRI showed injuries in the basal ganglia/thalamus+brainstem and even the whole brain in neonates with severe HIE, while the neonates with moderate HIE had injuries in the cerebral watershed, with little involvement of the brainstem (P < 0.01).Conclusions There is a good correlation between the MRI scoring system and clinical grading in neonatal HIE, suggesting the system can help with the clinical diagnosis and grading of HIE.

  • ● CLINICAL RESEARCH
    HUANG Li-Li, YANG Fan, XIONG Fei
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    Objective To investigate the association of leptin, adiponectin, and ghrelin in breast milk with the weight growth velocity of infants with exclusive breastfeeding.Methods A total of 67 full-term singleton infants who received regular child care and exclusive breastfeeding and their mothers were enrolled. The nutritional status was evaluated based on the measurements of body weight and body length (underweight, growth retardation, emaciation, overweight, and obesity). Z score was used to calculate growth velocity, and according to the ΔZ score, the infants were divided into poor growth group, low growth velocity group, and normal growth velocity group. Mature breast milk samples were collected from their mothers, and ELISA was used to measure the levels of leptin, adiponectin, and ghrelin.Results The emaciation group had a significantly lower level of leptin in breast milk than the non-emaciation group (P < 0.05), and the overweight/obesity group had a significantly lower level of adiponectin than the non-overweight/obesity group (P < 0.05). The correlation analysis showed that the level of ghrelin in breast milk was positively correlated with Z score of current body weight and ΔZ score compared with birth weight (rs=0.280 and 0.290 respectively; P < 0.05). The regression analysis showed that the level of ghrelin in breast milk was an important influencing factor for the Z score of body weight (β=0.161, P < 0.05).Conclusions Various active constituents in breast milk, including leptin, adiponectin, and ghrelin, may regulate the growth and development of infants to a certain degree, but long-term studies and observation are needed to investigate their association with offspring growth and development and the health-promoting effect of breast milk on offspring.

  • ● CLINICAL RESEARCH
    NI Wen-Si, ZHANG Yong-Hong, LI Ting, ZHAO Dong-Ying, TAN Jin-Tong, ZHU Tian-Wen, XIE Li-Juan
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    Objective To investigate the effect of early rehabilitation intervention on the incidences of extrauterine growth retardation (EUGR) and early diseases in preterm infants.Methods The appropriate-for-gestational-age preterm infants with a gestational age of < 34 weeks and a birth weight of 1 000 to < 2 000 g who were admitted to the neonatal intensive care unit (NICU) within 24 hours after birth were enrolled in a prospective randomized controlled trial. These infants were randomly divided into rehabilitation intervention group and control group. The infants in the rehabilitation intervention group were given early rehabilitation after their vital signs became stable, including oral sensory and muscle strength training and pressure touching of the head, chest, abdomen, extremities, hands, and feet. The primary outcome measures were the time to independent oral feeding, length of hospital stay, and incidence rate of EUGR. The secondary outcome measures were the incidence rates of related diseases in preterm infants, such as apnea, feeding intolerance, and sepsis.Results A total of 97 preterm infants who met the inclusion criteria and had complete data were enrolled, with 48 in the control group and 49 in the rehabilitation intervention group. The rehabilitation intervention group had a shorter time to independent oral feeding than the control group (P < 0.05). Compared with the control group, the rehabilitation intervention group had a shorter length of hospital stay and a lower corrected gestational age at discharge (P < 0.05), as well as a lower incidence rate of EUGR (P < 0.05). The rehabilitation intervention group had lower incidence rates of apnea, feeding intolerance, and sepsis than the control group (P < 0.05).Conclusions Early rehabilitation intervention for preterm infants in the NICU may reduce the incidence rates of apnea, feeding intolerance, and EUGR and help them to achieve independent oral feeding early.

  • ● CLINICAL RESEARCH
    BI Hong-Juan, XU Jing, WEI Qiu-Fen
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    Objective To investigate the role of donor human milk in the prevention of nosocomial infection in very low birth weight infants.Methods A total of 105 hospitalized preterm infants with a very low birth weight were enrolled. They were classified into mother's own milk feeding group, donor human milk feeding group, and preterm formula feeding group, with 35 infants in each group. The three groups were compared in terms of incidence rates of nosocomial infection, necrotizing enterocolitis, and feeding intolerance, time to full enteral feeding, and early growth indices.Results Compared with the preterm formula feeding group, the donor human milk feeding group and the mother's own milk feeding group had significantly lower incidence rates of nosocomial infection and necrotizing enterocolitis and shorter time to full enteral feeding (P < 0.05). There were no significant differences in head circumference, body length, and weight growth velocity among the three groups.Conclusions Donor human milk can be used in case of a lack of mother's own milk and may help to reduce nosocomial infection.

  • ● CLINICAL RESEARCH
    QIN Yan-Ran, LIU Cheng-Jun, XU Feng, LI Jing, XIONG Xiao-Yu
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    Objective To investigate the association between vasoactive-inotropic score (VIS) and prognosis in children with septic shock.Methods A total of 117 children with decompensated septic shock who received the treatment with vasoactive agents were enrolled. According to their prognosis, they were divided into death group with 41 children and survival group with 76 children. With the maximum VIS within the first 24 hours (24hVIS max) as the cut-off value (29.5), the children were divided into low VIS group with 78 children and high VIS group with 39 children. The 24hVIS max and the mean VIS within the first 24 hours (24hVIS mean) were calculated for all children. A receiver operating characteristic (ROC) curve analysis was performed for the association between VIS and the prognosis of septic shock.Results Compared with the survival group, the death group had significantly higher 24hVIS max, 24hVIS mean, PRISM Ⅲ score, and level of lactate before the use of vasoactive agents and after 24 hours of use (P < 0.05). 24hVIS max, 24hVIS mean, PRISM Ⅲ score, level of lactate before the use of vasoactive agents and after 24 hours of use, and 24-hour pH had a certain value in predicting the prognosis of septic shock, but 24hVIS max had the largest area under the ROC curve. Compared with the low VIS group, the high VIS group had significantly higher number of deaths, PRISM Ⅲ score, and level of lactate before treatment and after 24 hours of treatment (P < 0.05).Conclusions VIS is associated with the mortality of children with septic shock, and the severity and mortality of patients increase with the increase in VIS.

  • ● CLINICAL RESEARCH
    PENG Fang, ZHONG Li-Li, LIN Xiao-Juan, CHEN Min, ZHOU Miao
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    Objective To investigate the distribution characteristics and clinical features of Burkholderia cepacia infection in children.Methods A retrospective analysis was performed for the clinical data of 16 children with Burkholderia cepacia infection who were hospitalized between June 2012 and September 2017.Results All 16 children with Burkholderia cepacia infection were sporadic cases. A total of 16 strains of Burkholderia cepacia were isolated, among which 8 were detected by sputum culture, 5 were detected by blood culture, 2 were detected by tracheal intubation tip culture, and 1 was detected by lung biopsy culture. Of the 16 children, there were 11 boys and 5 girls, with an age of 5 days to 6 years, and the children aged < 1 year accounted for 69%. As for department distribution, 10 children were in the PICU/NICU and 6 were in the general wards. As for clinical manifestations, one child had disseminated intravascular coagulation, and the other 15 children had pulmonary infection, among who 11 had severe pneumonia (8 of them underwent mechanical ventilation during treatment). As for underlying diseases, 2 had severe congenital heart disease, 4 had primary immunodeficiency, 3 were highly suspected of immunodeficiency or inherited metabolic diseases, 1 had tracheal stenosis, 1 had Kawasaki disease, 1 was a preterm infant with bronchopulmonary dysplasia, 1 had severe cleft lip and palate, and 3 had no definite underlying diseases. Of all the children, 7 also had infections with adenovirus and Mycoplasma. The average length of hospital stay was 20.3 days for all children, and 12 were improved and 4 died after treatment. All 16 strains of Burkholderia cepacia had a drug resistance rate of 100% to amikacin and gentamicin and ≥ 80% to ampicillin/sulbactam and ticarcillin/clavulanic acid, as well as the lowest drug resistance rate o levofloxacin.Conclusions Burkholderia cepacia is an opportunistic pathogen often found in immunocompromised children and can produce drug resistance. The presence or absence of underlying diseases should be considered during anti-infective therapy. The children with Burkholderia cepacia infection often have a poor prognosis, and an understanding of the disease spectrum of Burkholderia cepacia infection helps with clinical diagnosis and treatment.

  • ● CLINICAL RESEARCH
    CHEN Qi-Fen, ZHANG Yi-Wei
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    Objective To investigate the clinical effect of Saccharomyces boulardii powder combined with azithromycin sequential therapy in the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia.Methods A total of 88 children with diarrhea secondary to Mycoplasma pneumoniae pneumonia between June 2015 and March 2017 were divided into control group and study group using a random number table, with 44 children in each group. The children in the control group were given routine treatment combined with azithromycin sequential therapy, and those in the study group were given oral Saccharomyces boulardii powder in addition to the treatment in the control group until the end of azithromycin sequential therapy. After the treatment ended, the two groups were compared in terms of time to improvement of clinical symptoms, length of hospital stay, clinical outcome, defecation frequency before and after treatment, condition of intestinal dysbacteriosis, and incidence of adverse events.Results Compared with the control group, the study group had significantly shorter time to improvement of clinical symptoms and length of hospital stay (P < 0.05). The study group had a significantly higher response rate than the control group (P < 0.05). On days 3 and 5 of treatment, the study group had a significant reduction in defecation frequency compared with the control group (P < 0.05). The study group had a significantly lower rate of intestinal dysbacteriosis than the control group (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups (P > 0.05).Conclusions In the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia, Saccharomyces boulardii powder combined with azithromycin sequential therapy can improve clinical symptoms, shorten the length of hospital stay, reduce defecation frequency and the incidence of intestinal dysbacteriosis, and improve clinical outcomes, and does not increase the risk of adverse events.

  • ● CLINICAL RESEARCH
    CHEN Xiu-Qi, TAN Wen-Hai, JIANG Fang-Fang, CHEN Xun
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    Objective To investigate the clinical features of invasive pulmonary fungal infections (IPFIs) after biliary atresia (BA) surgery and related risk factors.Methods A retrospective analysis was performed for the clinical data of 49 children with IPFIs after BA surgery, including clinical features, lung imaging findings, and pathogenic features. The risk factors for IPFIs after BA surgery were also analyzed.Results The most common pathogens of IPFIs after BA surgery was Candida albicans (17 strains, 45%), followed by Candida tropicalis (7 strains, 18%), Aspergillus (6 strains, 16%), Candida krusei (3 strains, 8%), Candida glabrata (3 strains, 8%), and Candida parapsilosis (2 strains, 5%). Major clinical manifestations included pyrexia, cough, and shortness of breath, as well as dyspnea in severe cases; the incidence rate of shortness of breath reached 78%, and 35% of all children had no obvious rale. The multivariate logistic regression analysis showed that age at the time of surgery, time of glucocorticoid application, cumulative time of the application of broad-spectrum antibiotics, and recurrent cholangitis were major risk factors for IPFIs after BA surgery.Conclusions The three most common pathogens of IPFIs after BA surgery are Candida albicans, Candida tropicalis, and Aspergillus. It is important to perform surgery as early as possible, avoid recurrent cholangitis, and shorten the course of the treatment with broad-spectrum antibiotics and glucocorticoids for decreasing the risk of IPFIs.

  • ● CLINICAL RESEARCH
    WEI Chun-Miao, XIA Gui-Zhi, REN Rong-Na
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    Objective To investigate the characteristics of gene mutations in unexplained infantile epileptic encephalopathy (EE).Methods A total of 47 infants with unexplained infantile EE were enrolled, and next-generation sequencing was used to analyze gene mutations in these infants and their parents.Results Of all 47 infants, 23 were found to have gene mutations, among whom 13 had de novo mutations and 10 had heterozygous mutations inherited from their father or mother. Among the 23 infants with gene mutations, 17 were found to have the gene mutations related to EE (among whom 14 had ion channel gene mutations), 2 had the gene mutations related to congenital inherited metabolic diseases, 2 had the gene mutations related to brain structural abnormality, and 2 had the gene mutations related to mental retardation.Conclusions Unexplained infantile EE may have gene mutations, mainly ion channel gene mutations.

  • ● CLINICAL RESEARCH
    A Qi-Ling, WANG Bo, CHEN Guang-Fu, HUANG Jian-Lin, LI Yun, CAO De-Zhi, LIU Rong-Tian
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    Objective To investigate the association between SCN1A rs3812718 polymorphism and generalized epilepsy with febrile seizures plus (GEFS+), and to provide potential molecular targets for the diagnosis and treatment of GEFS+.Methods The iPLEX technique in the MassARRAY system was used to determine SCN1A rs3812718 polymorphism, genotype frequency, and allele frequency in 50 patients with GEFS+ and 50 healthy controls.Results As for the frequencies of CC, CT, and TT genotypes in SCN1A rs3812718, there was a significant difference in the frequency of TT genotype between the GEFS+ group and the control group (P < 0.05). There was also a significant difference in the frequency of T allele between the two groups (P < 0.05). Compared with those carrying CC genotype or C allele, the individuals with CT genotype, TT genotype or T allele had a higher risk of developing GEFS+ (CT/CC:OR=4.05, 95% CI:1.04-15.69; TT/CC:OR=30.60, 95% CI:6.46-144.85; T/C:OR=4.64, 95% CI:2.54-8.48).Conclusions SCN1A rs3812718 polymorphism is a risk factor for GEFS+, and the population carrying T allele may have an increased risk of GEFS+.

  • ● CLINICAL RESEARCH
    LIN Qiong-Xi, WU Gui-Hua, ZHANG Ling, WANG Zeng-Jian, PAN Ning, XU Cai-Juan, JING Jin, JIN Yu
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    Objective To explore the recognition ability and abnormal processing characteristics to basic emotional faces in the early phase in children with autism spectrum disorders (ASD).Methods Photos of Chinese static faces with four basic emotions (fearful, happy, angry and sad) were used as stimulus. Twenty-five ASD children and twenty-two age-and gender-matched typical developed children (normal controls) were asked to match the emotional faces with words. Event-related potential (ERP) data were recorded concurrently.Results N170 latencies for total emotion and fearful face in the left temporal region were faster than in the right one in normal controls (P < 0.05), but the results were not noted in ASD children. Further, N170 latencies in the left temporal region of ASD children were slower than normal controls for total emotion, fearful and happy faces (P < 0.05), and their N170 latencies in the right temporal region were prone to slower than normal controls for angry and fearful faces.Conclusions The holistic perception speed of emotional faces in the early cognitive processing phase in ASD children is slower than normal controls. The lateralized response in the early phase of recognizing emotional faces may be aberrant in children with ASD.

  • ● CLINICAL RESEARCH
    SU Ting, LI Yu-Ling, Enherbayaer
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    Objective To investigate the association between dopamine D4 receptor gene DRD4 exon Ⅲ 48bp variable number of tandem repeat (VNTR) polymorphism and temperament in school-aged children.Methods Randomized cluster sampling was used to select 350 healthy children aged 8-12 years, and a questionnaire survey was performed. Oral epithelial samples were collected from half of these children. The complete questionnaire data of 164 children with a high level of DNA in oral epithelial samples were included in this study. PCR was used for the typing of DRD4 exon Ⅲ 48bp VNTR, and the effect of this gene and its interaction with the environment on temperament was analyzed.Results Compared with the children with S-DRD4 genotype, the children with L-DRD4 genotype had significantly lower scores on the four dimensions of activity level, reaction intensity, emotion essence, and persistence (P < 0.05). The main effects of mother's rejection/denial (OR=2.281, P < 0.05) and sex (OR=2.766, P < 0.05) and the interaction between sex and DRD4 exon Ⅲ 48bp VNTR (OR=0.582, P < 0.05) had an influence on activity level. The main effect of DRD4 exon Ⅲ 48bp VNTR (OR=0.314, P < 0.01) and the interaction between this gene and mother's rejection/denial (OR=1.872, P < 0.01) had an influence on reaction intensity. The main effect of DRD4 exon Ⅲ 48bp VNTR (OR=0.420, P < 0.05) and mother's rejection/denial (OR=2.236, P < 0.05) had an influence on persistence.Conclusions DRD4 exon Ⅲ 48bp VNTR and its interaction with other factors may affect the activity level and reaction intensity of school-aged children.

  • ● CLINICAL RESEARCH
    HU Nan, LI Qu-Bei, ZOU Shan-Ye
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    Objective To investigate the effect and safety of vitamin A supplementation in children with pneumonia through a systematic review.Methods Cochrane Library, EMbase, PubMed, China Biology Medicine disc, CNKI, and Wanfang Data were searched for randomized controlled trials (RCTs) on vitamin A as an adjuvant therapy for pneumonia in children. Two reviewers independently screened the studies and evaluated their quality according to the inclusion and exclusion criteria. RevMan5.3 was used for the Meta analysis.Results A total of 15 RCTs with 3 021 patients were included. The Meta analysis showed that vitamin A supplementation did not reduce the mortality of children with pneumonia (P > 0.05), but it increased the overall clinical response rate (P < 0.05) and shortened the duration of pyrexia and cough, clearance time of signs and abnormal chest X-ray results, and length of hospital stay (P < 0.05). As an adjuvant therapy, vitamin A did not increase the incidence rates of adverse reactions such as nausea, vomiting, diarrhea, allergy, and bregma bulging.Conclusions Current evidence shows that in the treatment of pneumonia in children, vitamin A supplementation helps to relieve clinical symptoms and signs and shorten the length of hospital stay.The adjuvant therapy does not increase the incidence rates of adverse reactions.

  • CASE ANALYSIS
  • ● CASE ANALYSIS
    IONG Juan, PENG Jing, DUAN Hao-Lin, CHEN Chen, WANG Xiao-Le, CHEN Shi-Meng, YIN Fei
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    A 4-month-old girl developed convulsion in the neonatal period, which was focal motor seizures in the initial stage and later became spasm and tonic spasm. And the girl also had psychomotor retardation and recurrent pulmonary infection. Electroencephalography showed hypsarrhythmia, normal results were obtained from cranial magnetic resonance imaging, cerebrospinal fluid examination, and urine organic acid analysis, as well as the spectral analyses of blood ammonia, blood lactic acid, blood amino acids, and acylcarnitines. Gene detection revealed a de novo heterozygous mutation, c.607G>A (p.G203R), in GNAO1. The girl was then diagnosed with GNAO1-associated early infantile epileptic encephalopathy (EIEE type 17). The seizures were well controlled by topiramate and vigabatrin, but there was no improvement in psychomotor development. She also suffered from recurrent pulmonary infection and died at the age of 12 months due to severe pneumonia. For children with unexplained early infantile epileptic encephalopathy, GNAO1 gene mutations should be considered and genetic tests should be performed as early as possible. Recurrent pulmonary infection should also be taken seriously.

  • EXPERIMENTAL RESEARCH
  • ● EXPERIMENTAL RESEARCH
    LIU Chang, JING Ke
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    Objective To investigate the effects of Toll-like receptor blockers TLR2-Ab and TLR4-Ab on the tight junction protein ZO-1 in intestinal epithelial cells in mice, as well as their effects on nuclear factor-kappa B (NF-κB) and tumor necrosis factor-α (TNF-α).Methods A total of 32 BALB/C mice were divided into control group, model group, TLR4 treatment group, and TLR2 treatment group, with 8 mice in each group. A mouse model of endotoxemia was established by intraperitoneal injection of lipopolysaccharide. The mice in the TLR4 treatment group and the TLR2 treatment group were given intraperitoneal injection of TLR4 antibody and TLR2 antibody (10 μg each mouse), respectively, and those in the control group were given normal saline. The distal small intestinal tissue was collected, and RT-PCR and immunohistochemistry were used to measure the mRNA and protein expression of ZO-1, NF-κBp65, and TNF-α.Results Compared with the control group, the model group had significantly lower mRNA and protein expression of ZO-1 and significantly higher mRNA expression of NF-κBp65 and TNF-α (P < 0.05). Compared with the model group, the TLR4 treatment group and the TLR2 treatment group had significantly higher mRNA and protein expression of ZO-1 and significantly lower mRNA and protein expression of NF-κBp65 and TNF-α (P < 0.05). There were no significant differences in the mRNA and protein expression of ZO-1, NF-κBp65, and TNF-α between the TLR4 treatment group and the TLR2 treatment group (P > 0.05).Conclusions Anti-TLR2 and anti-TLR4 monoclonal antibodies can reduce the activation of nuclear transcription factors, inhibit the secretion of inflammatory factors, and protect tight junction protein, which is expected to provide new ideas for the treatment of enterogenous infectious diseases.

  • REVIEW
  • ● REVIEW
    GAN Xin, LI Juan
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    Necrotizing enterocolitis (NEC) is a catastrophic disease caused by a variety of factors in neonates, especially preterm infants. Severe NEC has a high fatality rate, and most survivors may face short-and long-term adverse prognosis. Risk factors for NEC include preterm birth, non-breastfeeding, microbial abnormalities in the digestive tract, and ischemia-reperfusion injury. High-resolution abdominal ultrasound helps with the early diagnosis of NEC. The preventive measures for NEC include protecting the intestinal mucosa through nutritional intervention, interfering with intestinal injury signals, changing intestinal microflora, and performing early minimal enteral nutrition. This disease progresses rapidly, and there are still no effective measures. Supportive care is mainly used for the treatment of this disease, and patients in severe conditions may need surgical treatment. Celastrol, lipopolysaccharide, and fecal transplantation help with the treatment of NEC, but further studies are needed to confirm their clinical effects.