Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases in neonates especially in preterm infants. It is also the main reason leading to a poor prognosis. The prognosis of the neonates with BPD is unsatisfactory with current treatment strategies. Recent clinical trails have found that mesenchymal stem cell (MSC) transplantation might be effective and promising for treatment of BPD in neonates. This article outlines the characteristics of MSC and the potential mechanisms of MSC transplantation for BPD in vivo, and the safety and feasibility of MSC transplantation in BPD neonates, as well as the challenges in clinical trials on MSC transplantation for treatment of BPD.

Objective To investigate the physical development, incidence of common respiratory diseases, and motor development during infancy in preterm infants with bronchopulmonary dysplasia (BPD). Methods A retrospective analysis was performed on the clinical features and infantile outcomes of preterm infants with BPD who were admitted to the neonatal intensive care unit between January 2012 and December 2015. Preterm infants without BPD were used as controls who were admitted to the neonatal intensive care unit during the same period and had similar gestational age and birth weight. Physical development, number of hospital stays, the incidences of pneumonia and wheezing, and motor development during infancy were compared between the two groups. Results Compared with the control group, BPD infants had a significantly higher incidence of extrauterine growth retardation at discharge (48% vs 41%; P < 0.05); BPD infants were more susceptible to pneumonia, wheezing, eczema and rhinitis; BDP infants also had a significantly higher number of readmissions due to respiratory tract infection (P < 0.05). BPD infants had a significantly smaller head circumference than the control group at corrected ages of 3, 6, and 12 months (P < 0.05). BPD infants had significantly delayed gross, fine, and overall motor development than the control group at corrected ages of 6 and 9 months (P < 0.05). Conclusions Infants with BPD are susceptible to extrauterine growth retardation at discharge. Their head circumference growth is relatively slow. They are susceptible to pneumonia and wheezing during infancy. Moreover, they have delayed motor development when compared with those without BPD at corrected ages of 6 and 9 months.

Objective To explore the clinical value of arterial blood lactate level in predicting the prognosis of neonatal sepsis. Methods The clinical data of 301 cases of neonatal sepsis were collected, which mainly included biochemical indicators such as blood lactate on admission, C-reactive protein, and procalcitonin. ROC curves were plotted to evaluate the value of lactate level on admission in predicting the prognosis of neonatal sepsis. Results The mortality rate was significantly higher for full-term infants in the severely-elevated lactate group than in the mildly-elevated lactate group and the normal lactate group (26.1% vs 3.1% and 0%; P < 0.017). The poor prognosis group had a significantly increased lactate level on admission compared with the good prognosis group (6.5±5.1 mmol/L vs 3.6±1.7 mmol/L; P < 0.05). The sensitivity and specificity of blood lactate level on admission (cutoff value:6.15 mmol/L) were 0.545 and 0.919 respectively, in predicting the prognosis of neonatal sepsis. Conclusions Early blood lactate level can be used as a biochemical parameter to predict the prognosis of neonatal sepsis as it has a high specificity but a low sensitivity.

Objective To study the effect of red blood cell (RBC) storage duration on the clinical effect of exchange transfusion (ET) and internal environment in neonates with hyperbilirubinemia. Methods A retrospective analysis was performed for the clinical data of 135 neonates with hyperbilirubinemia who received ET between January 2015 and August 2018. According to RBC storage duration, the neonates were divided into short-term storage group (RBCs were stored for ≤ 7 days) with 56 neonates and long-term storage group (RBCs were stored for > 7 days) with 79 neonates. The two groups were compared in terms of serum total bilirubin (TBIL) level and the rate of TBIL reduction at 0 and 12 hours after ET, as well as the duration of continued phototherapy and rate of repeated ET. Routine blood test parameters, electrolytes, blood glucose, and blood gas parameters were measured before ET and at 0 hour after ET. Results At 0 hour after ET, there were no significant differences in the TBIL level and the rate of TBIL reduction between the two groups (P > 0.05). At 12 hours after ET, the long-term storage group had a significantly higher TBIL level and a significantly lower rate of TBIL reduction than the short-term storage group (P < 0.01). The long-term storage group had a significantly longer duration of continued phototherapy after ET than the short-term storage group (P < 0.05). Compared with the short-term storage group, the long-term storage group had significantly higher incidence rates of ET-related complications, including hyponatremia, hyperkalemia, and metabolic acidosis (P < 0.05). Conclusions The use of RBCs with a storage duration of > 7 days in ET for neonates with hyperbilirubinemia does not affect the immediate effect of ET, but these neonates tend to have a poor outcome after continued phototherapy and high risk of hyponatremia, hyperkalemia, and metabolic acidosis.

Objective To explore the value and significance of the clinical application of whole exome sequencing (WES) in monogenic hereditary disorders in critically ill newborns. Methods The critically ill newborns in the neonatal intensive care unit with suspected hereditary diseases or unclear clinical diagnosis from June 2016 to December 2018 were enrolled. The whole blood samples from both newborns and parents were collected for WES. The detected genetic mutations were classified, the mutations associated with clinical phenotypes were searched for, and Sanger sequencing was performed to verify the mutations. Results A total of 45 newborns were enrolled, including 22 males and 23 females, and the median age of onset was 2.0 days. Of the 45 newborns, 12 (27%) were confirmed with monogenic hereditary disorders by molecular diagnostics, and the median age at diagnosis was 31.5 days. Of the 12 newborns with monogenic hereditary disorders, 5 (42%) were partially associated with clinical phenotypes but confirmed with monogenic hereditary disorders by additional information supplement and analysis. The improvement rate of newborns with monogenic hereditary disorders was 67% (8/12) after treatment. Conclusions WES technology is a powerful tool for finding genetic mutations in monogenic hereditary disorders in critically ill newborns and can play a crucial role in clinical decision-making. However, a comprehensive interpretation of sequence data requires physicians to take the clinical phenotypes and the results of WES into consideration simultaneously.

Objective To study the clinical characteristics, drug sensitivity of isolated strains, and risk factors of drug resistance in children with invasive pneumococcal disease (IPD). Methods The clinical characteristics and drug sensitivity of the isolated strains of 246 hospitalized children with IPD in nine grade A tertiary children's hospitals from January 2016 to June 2018 were analyzed. Results Of the 246 children with IPD, there were 122 males and 124 females. Their ages ranged from 1 day to 14 years, and among them, 68 (27.6%) patients were less than 1 year old, 54 (22.0%) patients were 1 to 2 years old, 97 (39.4%) patients were 2 to 5 years old, and 27 (11.0%) patients were 5 to 14 years old. Pneumonia with sepsis was the most common infection type (58.5%, 144/246), followed by bloodstream infection without focus (19.9%, 49/246) and meningitis (15.0%, 37/246). Forty-nine (19.9%) patients had underlying diseases, and 160 (65.0%) had various risk factors for drug resistance. The isolated Streptococcus pneumoniae strains were 100% sensitive to vancomycin, linezolid, moxifloxacin, and levofloxacin, 90% sensitive to ertapenem, ofloxacin, and ceftriaxone, but had a low sensitivity to erythromycin (4.2%), clindamycin (7.9%), and tetracycline (6.3%). Conclusions IPD is more common in children under 5 years old, especially in those under 2 years old. Some children with IPD have underlying diseases, and most of the patients have various risk factors for drug resistance. Pneumonia with sepsis is the most common infection type. The isolated Streptococcus pneumoniae strains are highly sensitive to vancomycin, linezolid, moxifloxacin, levofloxacin, ertapenem, and ceftriaxone in children with IPD.

Objective To determine the high-risk factors for early failure of high-flow nasal cannula (HFNC) oxygen therapy in children with acute respiratory insufficiency (ARI). Methods The clinical data of 123 children with ARI were reviewed who received HFNC oxygen therapy in the pediatric intensive care unit from January to June, 2018. The children who did not require an upgrade of respiratory support during hospitalization and were successfully weaned from HFNC were classified as HFNC success group (69 cases). Of the remaining children (54 cases) who required an upgrade of their respiratory support during hospitalization, those that needed to upgrade their respiratory support within 48 hours of receiving HFNC were classified as early HFNC failure group (46 cases). Risk factors for early failure of HFNC were determined using multivariate logistic regression analysis. Results The incidence rates of shock, sepsis, intracranial hypertension syndrome, and multiple organ dysfunction syndrome were significantly higher in the early HFNC failure group than in the HFNC success group (P < 0.05). Before implementation of respiratory support, the early HFNC failure group had significantly lower Glasgow coma score, pH value, and oxygenation index and significantly higher Pediatric Risk of Mortality (PRISM) score and PaCO₂/PaO₂ ratio than the HFNC success group (P < 0.05). Multivariate logistic regression analysis showed that PRISM score > 4.5 and PaCO₂/PaO₂ ratio > 0.64 were independent risk factors for early HFNC failure (OR=5.535 and 9.089 respectively; P < 0.05). Conclusions Pediatric ARI patients with PRISM score > 4.5 or PaCO₂/PaO₂ ratio > 0.64 have relatively high risk of early HFNC failure.

Objective To compare the effect and safety of prednisolone and adrenocorticotropic hormone (ACTH) in the treatment of infantile spasms (IS). Methods Cochrane Library, Embase, PubMed, China Biology Medicine Disc, CNKI, and Wanfang Data were searched for clinical studies on the comparison between prednisolone and ACTH in the treatment of IS. Literature screening, data extraction, and quality assessment were performed. Review Manager 5.3 was used for Meta analysis. Results Five clinical studies were included according to the inclusion criteria and exclusion criteria. Meta analysis showed that there was no significant difference in the spasm remission rate, spasm remission time, complicating infection rate, and irritability rate between the prednisolone and ACTH treatment groups (P > 0.05), but the disappearance rate of hypsarrhythmia in the electroencephalogram was higher in the ACTH treatment group than in the prednisolone treatment group (P < 0.05). Conclusions The available evidence shows no difference in the clinical efficacy of prednisolone versus ACTH in the treatment of IS. However, ACTH is superior to prednisolone in stabilizing EEG. The two therapies have no difference in the incidence of adverse reactions such as infection and irritability.

Objective To investigate the composition of gut microbiota and its correlation with the severity of behavior symptoms in children with autism spectrum disorder (ASD). Methods A total of 30 children with ASD were enrolled as the ASD group, and 20 healthy children matched for age and sex were enrolled as the healthy control group. Related clinical data were analyzed. The V3-V4 hypervariable regions of the bacterial 16S rRNA gene in fecal samples were sequenced. The severity of behavior symptoms in children with ASD was assessed using the autism behavior checklist. The Spearman's correlation analysis was used to investigate the correlation between gut microbiota and the severity of behavior symptoms in children with ASD. Results There was a significant difference in the composition of gut microbiota between the two groups. Compared with the healthy control group, the ASD group had significant reductions in Shannon index and Shannoneven index (P < 0.05), as well as a significant reduction in the percentage of Firmicutes and a significant increase in the percentage of Acidobacteria in feces (P < 0.05). In the ASD group, the dominant bacteria were Megamonas, Megasphaera, and Barnesiella, while in the healthy control group, the dominant bacteria were Eubacterium_rectale_group, Ezakiella, and Streptococcus. In the children with ASD, the abundance of Megamonas was positively correlated with the scores of health/physical/behavior and language communication (P < 0.05). Conclusions The development of ASD and the severity of behavior symptoms are closely associated with the composition of gut microbiota.

Objective To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT). Methods Children with a clinical diagnosis of early-onset CMT were selected for the study. Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed. Results A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (15%) had novel mutations. The new variant c.394C > G (p.P132A) of the MPZ gene was rated as "possibly pathogenic" and the new variant c.326A > G (p.K109R) of the MFN2 gene was rated as "pathogenic". Conclusions Early-onset CMT is mainly caused by PMP22 gene duplication mutation and MPZ gene mutations. The clinical phenotype is mainly CMT type 1, among which Dejerine-Sottas syndrome accounts for a considerable proportion.

Objective To compare the levels of short-chain fatty acids in enterobacteria-related metabolites in feces between infants with cholestatic hepatopathy and healthy infants. Methods Thirty infants with cholestatic hepatopathy were enrolled in this study as the disease group, while 30 healthy infants were enrolled as the control group. Fecal specimens were collected from the disease group before and after treatment and from the control group. Gas chromatography was used to quantitatively determine the content of short-chain fatty acids in the feces of both groups including acetic acid, propionic acid, butyric acid, isobutyric acid, and isovaleric acid. Results There were no significant differences in the concentrations of acetic acid and propionic acid between the control and disease groups before and after treatment, as well as no significant changes in the two markers in the disease group after treatment (P > 0.05). The disease group had a significantly increased concentration of butyric acid after treatment (P < 0.05). The concentrations of isobutyric acid and isovaleric acid in the control group were significantly higher than those in the disease group before and after treatment (P < 0.05). Conclusions Intestinal protein metabolites in infants with cholestatic hepatopathy are significantly different from those in healthy infants, whereas there is no significant difference with respect to carbohydrate metabolites.

Objective To preliminarily investigate the relationship between stimulatory G protein α subunit (GNAS) and thyroid hormone receptor α (THRA) gene mutations and clinical phenotypes in children with congenital hypothyroidism (CH). Methods A total of 70 children with CH diagnosed by neonatal screening were enrolled. Their peripheral blood samples were collected to extract genomic DNA. GNAS and THRA genes were screened for mutations using next-generation sequencing. Bioinformatics software was used to analyze the pathogenicity of gene mutations. Results Of the 70 children with CH, nine missense mutations (three known mutations and six novel mutations) in the GNAS gene were detected in three patients (4%), and one gene polymorphism, c.508A > G(p.I170V), in the THRA gene was detected in four patients. The analysis results of bioinformatics software and ACMG/AMP guidelines showed that the two GNAS gene mutations[c.301C > T(p.R101C) and c.334G > A(p.E112K)] were more likely to be pathogenic. Three children with GNAS gene mutations showed different degrees of hypothyroidism. Conclusions GNAS gene mutations are related to the development of CH, and children with CH have different clinical manifestations. THRA gene mutations may not be associated with CH.

This paper reports the clinical and genetic characteristics of a case of combined pituitary hormone deficiency type I (CPHD1) caused by POU domain, class 1, transcription factor 1 (POU1F1) gene variation. A 2 years and 3 months old girl mainly presented with short stature, special facial features of prominent forehead, enophthalmos, and short mandible, loose skin, central hypothyroidism, complete growth hormone deficiency, and anterior pituitary hypoplasia. Gene analysis identified a novel heterozygous mutation, c.889C > T (p.R297W), in POU1F1 gene, and this locus of her parents was wild-type. This mutation was analyzed as a possible pathogenic variant according to the guidelines of the American College of Medical Genetics and Genomics, which has not been previously reported in the literature and conforms to the autosomal dominant inheritance. This child was diagnosed with CPHD1. Her height increased by 19.8 cm and showed a catch-up growth trend after one year of combined treatment with growth hormone and euthyrox. This study enriches the mutation spectrum of POU1F1 gene and has important significance for the diagnosis and classification of combined pituitary hormone deficiency.

Objective To study the clinical features of acute lymphoblastic leukemia (ALL) in children with IKAROS family zinc finger 1 (IKZF1) deletion, and to observe the effect of increasing the intensity of chemotherapy on the prognosis of this disease. Methods A total of 278 children diagnosed with ALL between December 2015 and February 2018 were systematically treated according to the Chinese Children's Leukemia Group-ALL 2008 protocol (CCLG-ALL 2008). The patients were divided into an IKZF1-deleted group and a control group according to the presence or absence of IKZF1. The IKZF1-deleted group was treated with the regimen for high-risk group (HR) in the CCLG-ALL 2008 protocol, while the control group received different intensities of chemotherapy according to clinical risk classification. The clinical features and event-free survival rate (EFS) were compared between the two groups. Results A total of 24 (8.6%) cases of 278 children were found to have large deletions of exons of the IKZF1 gene. The IKZF1-deleted group had significantly higher proportions of cases with white blood cell count ≥ 50×10⁹/L at initial diagnosis, BCR-ABL1 fusion gene positive, minimal residual disease ≥ 10% on the 15th day of induction remission treatment, minimal residual disease-high risk and clinical risk classification-high risk compared with the control group (P < 0.05). The 3-year EFS rate (76%±10%) in the IKZF1-deleted group was lower than that in the control group (84%±4%), but with no significant difference between the two groups (P=0.282). The estimated 3-year EFS rate in the IKZF1-deleted-non-HR group (actually treated with the chemotherapy regimen for HR in the CCLG-ALL 2008 protocol) was 82%±12%, which was lower than that in the control-non-HR group (86%±5%), but there was no significant difference (P=0.436). Conclusions ALL children with IKZF1 deletion have worse early treatment response, and increasing the intensity of chemotherapy might improve the prognosis.

Objective To examine the changes in T wave and ST segment amplitude in the supine and standing electrocardiograms (ECG) of children with orthostatic hypertension (OHT) and to determine their clinical significance. Methods A total of 49 children with OHT were included in the OHT group. Forty-three age-and sex-matched healthy children were included in the control group. Heart rate and T wave and ST segment amplitude were measured in both groups. T wave amplitude and ST segment amplitude in supine ECG were compared with those in standing ECG within each group. The differences in supine vs standing T wave amplitude and ST segment amplitude were compared between the OHT and control groups. Results In the control group, T wave amplitude in leads aVR, V₁, and V₄-V₆ were significantly lower in standing ECG than in supine ECG (P < 0.05); ST segment amplitude in leads V₄ and V₅ were significantly higher in standing ECG than in supine ECG (P < 0.05). In the OHT group, T wave amplitude in leads Ⅱ, aVR, aVF, and V₄-V₆ were significantly lower in standing ECG than in supine ECG (P < 0.05); ST segment amplitude in lead Ⅱ was significantly higher in standing ECG than in supine ECG (P < 0.05). The differences in T wave amplitude in lead Ⅱ and V₆ between supine and standing ECG were significantly higher in the OHT group than in the control group (P < 0.05). Difference in T wave amplitude in lead V₆ between supine and standing ECG was a significant diagnostic marker for OHT (P < 0.05). This marker had 72.10% sensitivity and 57.10% specificity for the diagnosis of OHT at the optimal cut-off value of 0.105 mV. Conclusions Difference in T wave amplitude in lead V₆ between supine and standing ECG has certain diagnostic value for OHT.

Objective To study the structural features of intestinal flora in preterm rats with cognitive impairment and the association of the change in intestinal flora with cognitive impairment in preterm rats. Methods Sprague-Dawley rats at 16-17 days of gestation were intraperitoneally injected with lipopolysaccharide for two consecutive days to establish a model of cognitive impairment, and the rats treated with intraperitoneally injected phosphate-buffered saline were established as the control group. Cesarean section was performed on day 21 of gestation, and preterm rats were randomly assigned to healthy maternal rats for feeding. The place navigation test in the Morris water maze was used to evaluate cognition on day 30 after birth. According to the result, the preterm rats were divided into cognitive impairment group with 21 rats and normal control group with 10 rats. Hematoxylin and eosin staining was used to observe pathological changes of the hippocampus, and fecal samples were collected for 16S rRNA sequencing and analysis. A principal component analysis (PCA) was performed for intestinal flora. Results Compared with the normal control group, the cognitive impairment group showed degeneration and necrosis of a large number of neurons in the hippocampus. Compared with the normal control group, the cognitive impairment group had significant reductions in the abundance and diversity of intestinal flora (P < 0.05), with a significant increase in the abundance of Proteobacteria at the phylum level (P < 0.05), as well as significant reductions in the abundance of Prevotella and Lactobacillus and significant increases in the abundance of Staphylococcaceae and Oligella at the order, family, and genus levels (P < 0.05). PCA showed a significant difference in the composition of intestinal flora between the two groups. Conclusions There is a significant change in the structure of intestinal flora in preterm rats with cognitive impairment, which provides a basis for the treatment and intervention of microecological changes due to cognitive impairment after preterm birth.

Objective To construct the recombinant adenoviral vector carrying the rat interleukin-10 (rIL-10) gene, and to investigate whether it is stably expressed in bone marrow mesenchymal stem cells. Methods The rIL-10 gene was amplified by PCR from template rIL-10 cDNA, and the recovered 656 bp rIL-10 DNA fragment was cloned into pcDNA3.1 to construct pcDNA3.1-IL-10. Then HEK293 cells were transfected with pcDNA3.1-IL-10 and adenoviral vector for homologous recombination, and sequencing and PCR were used to evaluate whether recombination was successful. HEK293 cells were lysed by repeated freeze-thaw cycles, and bone marrow mesenchymal stem cells were infected with the virus solution containing the rIL-10 gene. Western blot was used to measure the expression of rIL-10 in bone marrow mesenchymal stem cells. Results Sequencing and PCR verified that the rIL-10 adenoviral vector was successfully constructed, with a virus titer of 4×10⁹ PFU/mL. The expression of IL-10 was detected after bone marrow mesenchymal stem cells were infected by the virus solution containing the rIL-10 gene. Conclusions The constructed rIL-10 recombinant adenovirus can mediate the stable expression of rIL-10 gene in bone marrow mesenchymal stem cells, which provides a basis for gene transplantation therapy of inflammatory bowel disease.

Patients with pertussis can have a variety of complications, including pneumonia and subconjunctival hemorrhage. Severe complications, such as pulmonary hypertension and encephalopathy, can be life-threatening. Younger children with pertussis may lack the characteristic clinical manifestations of pertussis, and therefore, a deeper understanding of the complications of pertussis may help to improve the diagnosis, treatment, and prognosis of pertussis. However, there is still no standard for the diagnosis and treatment of pertussis complications, and there are great differences in diagnostic name, basis, and data used in different reports. This article reviews the complications of pertussis which have been reported so far, such as pulmonary complications (pneumonia, pulmonary hypertension, pneumothorax, and mediastinal or subcutaneous emphysema), fractures, hernias, circulatory system complications, nervous system complications (convulsion, encephalopathy, hemorrhage, and hematoma), urinary system complications, and secondary infections, so as to provide a reference for the clinical diagnosis and treatment of pertussis complications, scientific research on pertussis complications, and the promotion of standardized diagnosis and treatment of pertussis complications.

Mammalian target of rapamycin (mTOR) is an intracellular signaling pathway molecule which regulates various fundamental physiological processes. The mTOR signaling pathway plays an important role in synaptic plasticity, information transmission and processing, and neuroregulation. Dysregulation of the mTOR signaling pathway is generally considered to be related to the pathogenesis of autism spectrum disorder (ASD); meanwhile, the mTOR inhibitor can ameliorate the symptoms of ASD. The role of mTOR in the pathogenesis of ASD is summarized in this article to provide a theoretical basis for targeted therapy of ASD.

The development of invasive mechanical ventilation technology provides effective respiratory support for critically ill children. However, respiratory support is not the end of treatment as the ultimate goal is successful extubation in children. At present, some evaluation indicators before extubation including rapid shallow breathing index, maximal inspiratory pressure, and work of breathing are of high clinical value in predicting adult extubation outcome, but their evidence of evidence-based medicine is not sufficient in the field of pediatric intensive care. This paper reviews the current research on the validity of predictors for extubation outcomes in children. It shows that there is still a lack of indicators with good sensitivity and specificity for assessment before extubation in children. The studies are still in a small-sample size and single-center stage. Therefore, how to optimize evaluation before extubation and improve the success rate of extubation is the direction of joint efforts of doctors in the pediatric intensive care unit and rehabilitation medicine department.