Bronchopulmonary dysplasia (BPD) is one of the few diseases affecting premature infants that have continued to evolve since its first description about half a century ago. The current form of BPD, a more benign and protracted respiratory failure in extremely preterm infants, is in contrast to the original presentation of severe respiratory failure with high mortality in larger premature infants. This new BPD is end result of complex interplay of various antenatal and postnatal factors causing lung injury and subsequent abnormal repair leading to altered alveolar and vascular development. The change in clinical and pathologic picture of BPD over time has resulted in new challenges in developing strategies for its prevention and management. While some of these strategies like Vitamin A supplementation, caffeine and volume targeted ventilation have stood the test of time, others like postnatal steroids are being reexamined with great interest in last few years. It is quite clear that BPD is unlikely to be eliminated unless some miraculous strategy cures prematurity. The future of BPD prevention will probably be a combination of antenatal and postnatal strategies acting on multiple pathways to minimize lung injury and abnormal repair as well as promote normal alveolar and vascular development.

Objective To study the effect of extensively hydrolyzed formula on the growth and development in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants.Methods A total of 375 VLBW or ELBW infants were enrolled and divided into an observation group (187 infants) and a control group (188 infants) using a random number table. The infants in the observation group were given extensively hydrolyzed formula, and when the amount of extensively hydrolyzed formula reached 10 mL/time, it was changed to the standard formula for preterm infants. The infants in the control group were given standard formula for preterm infants. Both groups were fed for 4 consecutive weeks and were compared in terms of incidence rate of feeding intolerance, time to establish full enteral feeding, time to complete meconium excretion, number of spontaneous bowel movements, growth and development, motilin level at 4 and 10 days after feeding, and incidence rate of infection.Results Compared with the control group, the observation group had a lower rate of feeding intolerance (P < 0.05), a shorter duration to full enteral feeding and time to complete meconium excretion (P < 0.05), a higher mean number of daily spontaneous bowel movements (P < 0.05), higher body weight (1 793±317 g vs 1 621±138 g; P < 0.05), head circumference (30.5±1.1 cm vs 30.0±1.6 cm; P < 0.05), and body length (43.9±1.2 cm vs 42.1±2.0 cm; P < 0.05), a higher motilin level at 4 and 10 days after feeding (P < 0.05), and a significantly lower infection rate (P < 0.05).Conclusions Extensively hydrolyzed formula can increase motilin level, improve gastrointestinal feeding tolerance, promote early growth and development, and reduce the incidence of infection in VLBW and ELBW infants.

Objective To investigate the effect and safety of extensively hydrolyzed formula (EHF) in preterm infants.Methods A total of 692 preterm infants between January 2007 and December 2016 were enrolled as subjects. According to the feeding pattern, they were divided into EHF group (327 infants) and standard preterm formula (SPF) group (365 infants). A retrospective analysis was performed for their clinical data during hospitalization, including the incidence of feeding intolerance, time to establish full enteral feeding, time to first excretion of meconium, time to complete excretion of meconium, presence or absence of intestinal infection or neonatal necrotizing enterocolitis (NEC), serum albumin level within 3 weeks after admission, and time to the appearance of skin jaundice and its duration.Results There were no significant differences between the two groups in the starting time of breastfeeding, time to first excretion of meconium, time to the appearance of skin jaundice, serum albumin level at weeks 1 and 2 after admission, and time to recovery of birth weight (P > 0.05). Compared with the SPF group, the EHF group had significantly lower incidence rates of feeding intolerance, intestinal infection, and NEC and a significantly lower positive rate of stool occult blood test (P < 0.05), as well as significantly shorter time to complete excretion of meconium, duration to establish full enteral feeding, duration of jaundice, and length of hospital stay (P < 0.05). At week 3 after admission, the EHF group had a significantly higher serum albumin level than the SPF group (P < 0.05).Conclusions EHF can reduce the incidence rates of feeding intolerance and NEC in preterm infants, shorten the duration of jaundice, promote defecation, and help them to achieve full enteral feeding early. It has significant advantages over SPF.

Objective To investigate the effect of premature rupture of membranes (PROM) on maternal infections and outcome of preterm infants.Methods A total of 441 preterm infants and 387 mothers were enrolled as subjects. According to the presence or absence of PROM, the mothers were divided into non-PROM group with 104 mothers, PROM duration < 72 hours group with 90 mothers, and PROM duration ≥72 hours group with 193 mothers. The three groups were compared in terms of clinical features of mothers and infants and complications.Results Compared with the control group and the PROM duration < 72 hours group, the PROM duration ≥72 hours group had significantly higher maternal age, incidence rate of umbilical vasculitis, and rate of antibiotic use; the PROM duration ≥72 hours group had a significantly higher incidence rate of moderate-to-severe chorioamnionitis than the control group (P < 0.05), while there was no significant difference between the PROM duration ≥72 hours group and the PROM duration < 72 hours group (P > 0.05). Compared with the control group and the PROM duration < 72 hours group, the PROM duration ≥72 hours group had significantly higher incidence rates of pneumonia and intracranial hemorrhage in preterm infants; the PROM duration ≥72 hours group had a significantly higher incidence rate of congenital infection and a significantly longer mean length of hospital stay compared with the control group (P < 0.05), while there were no significant differences between the PROM duration ≥72 hours group and the PROM duration < 72 hours group (P > 0.05). The multivariate analysis showed that PROM duration ≥72 hours was an independent risk factors for pneumonia (OR=2.200, 95%CI: 1.386-3.492) and intracranial hemorrhage (OR=2.331, 95%CI: 1.420-3.827) in preterm infants.Conclusions PROM duration ≥72 hours significantly increases the risk of placental infection in mothers and it is an independent risk factor for pneumonia and intracranial hemorrhage in preterm infants.

Objective To study the pathogen distribution and risk factors of nosocomial infection in very preterm infants, as well as the risk of adverse outcomes.Methods A retrospective analysis was performed for the clinical data of 111 very preterm infants who were born between January and December, 2016 and had a gestational age of < 32 weeks and a birth weight of < 1 500 g. According to the presence or absence of nosocomial infection after 72 hours of hospitalization, the infants were divided into infection group and non-infection group. The infection group was analyzed in terms of pathogenic bacteria which caused infection and their drug sensitivity. A multivariate logistic regression analysis was used to investigate the potential risk factors and risk of adverse outcomes of nosocomial infection in very preterm infants.Results Gram-negative bacteria were the main pathogens for nosocomial infection in very preterm infants and accounted for 54%, among which Pseudomonas aeruginosa was the most common one; the following pathogens were fungi (41%), among which Candida albicans was the most common one. The drug sensitivity test showed that Gram-negative bacteria were highly resistant to β-lactam and carbapenems and highly sensitive to quinolones, while fungi had low sensitivity to itraconazole and high sensitivity to 5-fluorocytosine and amphotericin B. Early-onset sepsis, duration of peripherally inserted central catheter, steroid exposure, and duration of parenteral nutrition were risk factors for nosocomial infection in very preterm infants (P < 0.05). Compared with the non-infection group, the infection group had significantly higher risks of pulmonary complications (P < 0.05), as well as a significantly longer length of hospital stay and a significantly higher hospital cost (P < 0.001).Conclusions Nosocomial infection in very preterm infants is affected by various factors and may increase the risk of adverse outcomes. In clinical practice, reasonable preventive and treatment measures should be taken with reference to drug sensitivity, in order to improve the prognosis of very premature infants.

Objective To investigate the value of combined determination of neutrophil CD64 and procalcitonin (PCT) in the early diagnosis of neonatal bacterial infection.Methods According to discharge diagnosis, 37 neonates with bacterial infection were divided into sepsis (n =15) and ordinary infection (non-sepsis) groups (n =22). Twenty-one neonates without infection who were hospitalized during the same period of time were enrolled as the control group. Venous blood samples were collected immediately after admission. Flow cytometry was used to measure the serum level of neutrophil CD64. Chemiluminescence and immune transmission turbidimetry were used to measure the serum levels of PCT and CRP respectively.Results The sepsis group had higher serum levels of neutrophil CD64, PCT, and CRP than the control group (P < 0.01), the ordinary infection group had a higher serum level of neutrophil CD64 than the control group (P < 0.01), and the sepsis group had higher serum levels of PCT and CRP than the ordinary infection group (P < 0.01). The areas under the ROC curve (AUC) of neutrophil CD64, PCT, and CRP in diagnosing bacterial infection were 0.818, 0.818, and 0.704 respectively, and the AUC of combined neutrophil CD64 and PCT was 0.926. A combination of neutrophil CD64 and PCT had a sensitivity of 97.29% and an accuracy of 89.65% in the early diagnosis of neonatal bacterial infection.The sensitivity and accuracy were higher than those of a combination of CRP and neutrophil CD64 or PCT as well as neutrophil CD64, PCT, or CRP alone for the early diagnosis of neonatal bacterial infection.Conclusions The combined determination of neutrophil CD64 and PCT can improve the sensitivity and accuracy in the diagnosis of neonatal bacterial infection, which helps with early identification of bacterial infection.

Objective To establish the intrauterine growth curves of neonates in Shenzhen, China and to investigate the intrauterine growth of neonates in Shenzhen.Methods Cross-sectional cluster sampling was performed for an on-the-spot investigation of 16 887 neonates (9 418 males and 7 469 females) with a gestational age of 27-42 weeks who were born in two hospitals in Shenzhen from April 2013 to September 2015. The Lambda Mu Sigma (LMS) method was used for the curve fitting of body weight, body length, head circumference, chest circumference, and crown-rump length.Results The 3rd-97th percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length were plotted for the neonates with a gestational age of 27-42 weeks who were divided into three groups (male, female, and mixed). The male neonates had significantly higher curves for the five indices than the female counterparts. The pattern and changing trend of body weight curves of these neonates were basically consistent with those in China Neonatal Network.Conclusions The percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length in neonates with a gestational age of 27-42 weeks in Shenzhen which has been established can provide a reference for clinical practice in the department of neonatology.

Objective To investigate whether fetal growth restriction (FGR) has an adverse effect on white matter development.Methods A total of 28 full-term small for gestational age (SGA) infants were enrolled as study subjects and 15 full-term appropriate for gestational age infants were enrolled as control group. Conventional head magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed for all infants. The white matter was divided into 122 regions. The two groups were compared in terms of fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of different brain regions.Results Compared with the control group, the SGA group had a significantly lower fractional anisotropy in 16 brain regions (P < 0.01), a significantly higher mean diffusivity in 7 brain regions (P < 0.05), a significantly higher axial diffusivity in 8 brain regions (P < 0.05), and a significantly higher radial diffusivity in 16 brain regions (P < 0.05).Conclusions FGR may cause abnormalities in the maturity and integrity of white matter fiber tracts.

Objective To investigate penis development in children and adolescents aged 0-16 years, and to plot the percentile curve for penis development in different age groups.Methods A total of 3 024 normal male neonates, children, and adolescents aged 0-16 years in Chongqing, China were selected by simple random sampling and stratified cluster sampling. The length and diameter of the penis were measured for all subjects. A descriptive statistical analysis was used to investigate the data characteristics of the penis, and the GAMLSS fitting model was used to plot the percentile curves of P₃, P₁₀, P₂₅, P₅₀, P₇₅, P₉₀, and P₉₇ and obtain percentile reference values.Results The length and diameter of the penis grew rapidly before the age of 1 year, grew relatively slowly from 1 to 11 years old, and entered a rapid growth period from 11 years old. The length of the penis was positively correlated with its diameter (r=0.961, P < 0.01). The percentile reference values of penis length and diameter were obtained and the percentile curve was plotted.Conclusions The growth and development of penis length is consistent with that of penis diameter in male children and adolescents in Chongqing, and 0-1 year and 11-16 years are rapid growth periods of penis length and diameter. The percentile curve of penis length and diameter in children and adolescents aged 0-16 years in Chongqing which has been established will provide a reference for further studies on sexual development in children and adolescents.

Objective To investigate the neurocognitive function of children with acute lymphoblastic leukemia (ALL) and long-term disease-free survival and related influencing factors.Methods A total of 40 ALL children with long-term disease-free survival were enrolled as study group, and 40 healthy children were enrolled as control group. The Chinese Wechsler Intelligence Scale for Children (C-WISC), continuous performance test (CPT), and Stroop test software were used for the evaluation of all children. Neurocognitive function was compared between groups and influencing factors were analyzed.Results Compared with the control group, the study group had significantly lower full intelligence quotient, verbal intelligence quotient, and performance intelligence quotient in C-WICS (P < 0.05) and significantly higher numbers of mistakes and misses in CPT (P < 0.05). There were no significant differences in the numbers of correct answers, mistakes, and misses of word-color consistency between the study group and the control group (P > 0.05), while the study group had significantly higher numbers of mistakes and misses of word-color contradiction and irrelevance (P < 0.05). The total dose of high-dose methotrexate and ALL risk classification were associated with the reduction in intelligence quotient, and children's younger age at diagnosis of ALL was associated with the higher numbers of misses and mistakes. Girls tended to have a significantly lower performance intelligence quotient than boys (P < 0.05).Conclusions ALL children with long-term disease-free survival have neurocognitive impairment, which may be associated with the dose of chemotherapeutic drugs, age at diagnosis, and sex.

Objective To investigate the association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71.Methods A total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children.Results The rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (P < 0.01). Children with severe HFMD caused by enterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (P < 0.05). Compared with the cured patients, the patients with poor prognosis had significant increases in the frequencies of TT genotype and T allele in the rs9722 locus of the S100B gene (P < 0.05). Among the 74 children with HFMD, the children with TT genotype had the highest serum level of S100B protein, and those with CC genotype had the lowest level (P < 0.01).Conclusions T allele in the rs9722 locus of the S100B gene might be a risk factor for severe HFMD caused by enterovirus 71 infection.

Objective To investigate the myocardial protective effect of L-carnitine in children with hand, foot and mouth disease (HFMD) caused by Coxsackie A16 virus and possible mechanisms.Methods A total of 60 HFMD children with abnormal myocardial enzyme after Coxsackie A16 virus infection were enrolled and randomly divided into L-carnitine group and fructose-1,6-diphosphate group (fructose group), with 30 children in each group. The two groups were given L-carnitine or fructose diphosphate in addition to antiviral and heat clearance treatment. Another 30 healthy children who underwent physical examination were enrolled as control group. The changes in myocardial zymogram, malondialdehyde (MDA), superoxide dismutase (SOD), and apoptosis factors sFas and sFasL after treatment were compared between groups.Results There was no significant difference in treatment response between the L-carnitine group and the fructose group (P > 0.05). One child in the fructose group progressed to critical HFMD, which was not observed in the L-carnitine group. Before treatment, the L-carnitine group and the fructose group had significantly higher indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significantly lower level of SOD than the control group (P < 0.05), while there were no significant differences in these indices between the L-carnitine group and the fructose group (P > 0.05). After treatment, the L-carnitine group and the fructose group had significant reductions in the indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significant increase in the level of SOD (P < 0.05); the fructose group had a significantly higher level of creatine kinase (CK) than the control group and the L-carnitine group, and there were no significant differences in other myocardial enzyme indices, MDA, sFas, and sFasL between the L-carnitine group and the fructose group, as well as between the L-carnitine and fructose groups and the control group (P > 0.05). SOD level was negatively correlated with aspartate aminotransferase, lactate dehydrogenase (LDH), CK, and creatine kinase-MB (CK-MB) (r=-0.437, -0.364, -0.397, and -0.519 respectively; P < 0.05), and MDA level was positively correlated with LDH and CK-MB (r=0.382 and 0.411 respectively; P < 0.05).Conclusions L-carnitine exerts a good myocardial protective effect in children with HFMD caused by Coxsackie A16 virus, possibly by clearing oxygen radicals and inhibiting cardiomyocyte apoptosis.

Infantile liver failure syndrome type 1 (ILFS1) is a Mendelian disease due to biallelic mutations in the cytoplasmic leucyl-tRNA synthetase gene (LARS). This study aimed to report the clinical and molecular features of the first non-caucasian ILFS1 patient, providing reliable evidences for the definite diagnosis of ILFS1. The 2 years and 9 months old male patient was referred to the hospital with hepatosplenomegaly over 1 year. At age 17 months, he was found to have hepatosplenomegaly and anemia. Since then, he had been managed in different hospitals. The laboratory tests showed liver dysfunction, hypoproteinemia, coagulopathy and anemia, along with histologically-confirmed cirrhosis and fatty liver; however, the etiology remained undetermined. The subsequent SLC25A13 mutation analysis by means of prevalent mutation screening and Sanger sequencing only revealed a paternally-inherited mutation c.1658G > A, and no aberrant SLC25A13 transcripts could be detected from the maternal allele on cDNA cloning analysis, ruling out the possibility of citrin deficiency. Further target exome high-throughout sequencing of genes relevant to genetic liver diseases detected a paternal c.2133_2135del (p.L712del) and a maternal c.1183G > A (p.D395N) mutation in LARS gene. This finding was then confirmed by Sanger sequencing, and ILFS1 was thus definitely diagnosed. The child has been followed up till age 4 years, and his condition became stabilized.

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Objective To investigate the effect of baicalin on the behavioral characteristics of rats with attention deficit hyperactivity disorder (ADHD), and to provide a basis for further research on baicalin in the treatment of ADHD.Methods A total of 40 SHR rats were randomly divided into model group, methylphenidate hydrochloride (MPH) group, and low-, medium-, and high-dose baicalin groups, with 8 rats in each group. Eight WKY rats were selected as normal control group. The rats in the MPH group (0.07 mg/mL) and the low- (3.33 mg/mL), medium- (6.67 mg/mL), and high-dose (10 mg/mL) baicalin groups were given the corresponding drugs (1.5 mL/100 g) by gavage twice a day, and those in the normal control group and the model group were given an equal volume of normal saline by gavage twice a day. The course of treatment was 4 weeks for all groups. The open field test was performed to observe total moving distance and average moving speed on day 0 of experiment and at 7, 14, 21, and 28 days after gavage and to evaluate the control effects of drugs on hyperactivity and impulsive behavior. The Morris water maze test was used to observe the latency, time spent in the target quadrant, and number of platform crossings and to evaluate the effects of drugs on attention.Results The open field test showed that the model group and the drug treatment groups had a significantly longer total moving distance and a significantly higher average moving speed than the normal control group on day 0 (P < 0.05). On day 7, the MPH group had significant reductions in total moving distance and average moving speed compared with the model group (P < 0.05). On day 14, the MPH group and the high-dose baicalin group had significant reductions in total moving distance and average moving speed compared with the model group (P < 0.05). The data on days 21 and 28 showed that compared with the model group, the low-, medium-, and high-dose baicalin groups had gradual reductions in total moving distance and average moving speed (P < 0.05). The water maze test showed that compared with the model group, the MPH group and the medium- and high-dose baicalin groups had a significantly longer time spent in the target quadrant (P < 0.05), and the MPH group and the high-dose baicalin group had a significantly higher proportion of the moving distance in the target quadrant in total moving distance (P < 0.05). The high-dose baicalin group had the highest number of platform crossings among all groups (P < 0.05).Conclusions Both baicalin and MPH can regulate the motor ability and learning and memory abilities of SHR rats with ADHD and thus control the core symptoms of ADHD, i.e., hyperactivity, impulsive behavior, and inattention. Baicalin exerts its effect in a dose-dependent manner, and high-dose baicalin has the most significant effect, but compared with MPH, it needs a longer time to play its therapeutic effect.

Objective To investigate the expression of autophagic gene and circadian gene in the neurons of neonatal rats after hypoxic-ischemic brain damage and the mechanism of nerve injury induced by hypoxia/ischemia.Methods Twelve Sprague-Dawley (SD) rats were randomly divided into hypoxic-ischemic (HI) group and sham-operation group, with 6 rats in each group. Ligation of the right common carotid artery and hypoxic treatment were performed to establish a model of hypoxic-ischemic brain damage. Western blot was used to measure the expression of the circadian protein Clock in the cortex and hippocampus. The neurons of the rats were cultured in vitro and randomly divided into oxygen glucose deprivation (OGD) group and control group. The neurons in the OGD group were treated with DMEM medium without glucose or serum to simulate ischemic state, and hypoxic treatment was performed to establish an in vitro model of hypoxic-ischemic brain damage. Western blot was used to measure the expression of autophagy-related proteins Beclin1 and LC3 and Clock protein at different time points. The changes in the expression of Beclin1 and LC3 were measured after the expression of Clock protein in neurons was inhibited by small interfering RNA technique.Results The expression of autophagy-related proteins Beclin1 and LC3Ⅱ in neurons cultured in vitro displayed a rhythmic fluctuation; after OGD treatment, the expression of Beclin1 and LC3Ⅱ gradually increased over the time of treatment and no longer had a rhythmic fluctuation. Compared with the sham-operation group, the HI group had a significant reduction in the expression of Clock protein in the cortex and hippocampus (P < 0.05). After OGD treatment, the neurons cultured in vitro had a significant reduction in the expression of Clock protein (P < 0.05). Compared with the negative control group, the Clock gene inhibition group had significant reductions in the expression of Beclin1 and LC3Ⅱ (P < 0.05).Conclusions Hypoxia/ischemia induces the disorder in the expression rhythm of autophagy-related proteins Beclin1 and LC3, and the mechanism may be associated with the fact that the circadian protein Clock participates in the regulation of the expression of Beclin1 and LC3.

Acute lymphoblastic leukemia (ALL) is the most common malignant hematological disease in childhood. Glucocorticoids are frequently used in the chemoradiotherapy regimen for ALL and can induce the apoptosis of ALL cells through several signaling pathways, but about 10% of ALL children have poor response to glucocorticoids. Studies have revealed that glucocorticoids induce the apoptosis of ALL cells by upregulating the expression of BIM gene, and BIM gene is associated with glucocorticoid resistance in childhood ALL. This article reviews the recent studies on glucocorticoid resistance in childhood ALL, especially the role of BIM and its expression products in this process.