Objective To investigate the incidence of late-onset sepsis (LOS) in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants in the neonatal intensive care unit (NICU) and the risk factors for LOS. Methods A retrospective analysis was performed for the clinical data of all VLBW and ELBW infants who were hospitalized in the NICU between January 2011 and December 2013. According to the presence or absence of LOS, these infants were divided into LOS group and non-LOS group. The incidence and mortality rates of LOS, common pathogenic bacteria, and risk factors for LOS were analyzed. Results Of the 226 VLBW and ELBW infants, 117 (51.8%) developed LOS, among whom 45 had a confirmed diagnosis of LOS and 72 had a clinical diagnosis of LOS. The LOS group had a significantly higher mortality rate than the non-LOS group[13.7% (16/117) vs 4.6% (5/109); P < 0.05]. Bacterial culture found 51 strains of pathogenic bacteria, among which 32 (63%) were Gram-negative bacteria, 16 (31%) were Gram-positive bacteria, and 3 (6%) were fungi. The multivariate logistic regression analysis showed that gestational age, small for gestational age (SGA), duration of parenteral nutrition, peripherally inserted central catheter (PICC) placement, and mechanical ventilation were independent risk factors for LOS in VLBW and ELBW infants (OR=0.84, 1.59, 1.34, 3.11, and 4.55 respectively; P < 0.05). Conclusions LOS has high incidence and mortality rates in VLBW and ELBW infants. Common pathogenic bacteria of LOS are Gram-negative bacteria. Low gestational age, long duration of parenteral nutrition, SGA, PICC placement, and mechanical ventilation may increase the risk of LOS in VLBW and ELBW infants.
Objective To investigate the relationship between serum 25-hydroxyvitamin D[25 (OH)D] levels at birth and respiratory distress syndrome (RDS) in preterm infants. Methods This retrospective study recruited preterm infants with gestational age of below 34 weeks who were born between January 2014 and December 2016. These preterm infants were divided into two groups:RDS (n=72) and control (n=40). Clinical data of the two groups were collected, including gestational age, birth weight, gender, delivery mode, Apgar scores at 1 minute and 5 minutes, incidence of maternal gestational diabetes mellitus, and use of prenatal steroid hormone. Peripheral blood samples were collected and 25 (OH)D levels were measured by chemiluminescence immunoassay. The association between serum 25 (OH)D levels at birth and RDS was analyzed by multivariate logistic regression. Results Apgar scores at 1 minute and 5 minutes and serum 25 (OH)D levels in the RDS group were significantly lower than those in the control group (P < 0.05), while the rates of neonatal asphyxia and vitamin D deficiency were significantly higher than those in the control group (P < 0.05). Multivariate logistic regression analysis showed that neonatal asphyxia (OR=2.633, 95%CI:1.139-6.085) and vitamin D deficiency (OR=4.064, 95%CI:1.625-10.165) were risk factors for RDS in preterm infants. Conclusions Vitamin D deficiency might be associated with increased risk of RDS in preterm infants. Reasonable vitamin D supplementation during pregnancy might reduce the incidence of RDS in preterm infants.
Objective To compare the efficacy and safety of different analgesic and sedative treatments in children with mechanical ventilation in the pediatric intensive care unit (PICU). Methods Eighty children with mechanical ventilation in the PICU who needed analgesic and sedative treatments were equally and randomly divided into midazolam group and remifentanil+midazolam group. The sedative and analgesic effects were assessed using the Ramsay Scale and the Face, Legs, Activity, Cry and Consolability (FLACC) Scale. The following indices were recorded for the two groups:vital signs, ventilator parameters, organ function, total doses of remifentanil and midazolam, duration of mechanical ventilation, length of PICU stay, PICU cost, and incidence of adverse events. Results Satisfactory sedation was achieved in the two groups, but the remifentanil+midazolam group had a significantly shorter time to analgesia and sedation than the midazolam group. The remifentanil+midazolam group had a significantly higher percentage of patients with grade 3-4 on the Ramsay Scale and a significantly lower dose of midazolam than the midazolam group (P < 0.05). Both groups showed decreases in heart rate (HR), mean arterial pressure (MAP), and spontaneous breathing frequency (RRs) after treatment. However, the remifentanil+midazolam group had significantly greater decreases in HR at 3-24 hours after treatment and MAP and RRs at 3-12 hours after treatment than the midazolam group (P < 0.05). Compared with the midazolam group, the remifentanil+midazolam group had significantly higher ventilator tidal volume and transcutaneous oxygen saturation at 6 and 12 hours after treatment and significantly lower end-tidal carbon dioxide partial pressure at 6 and 12 hours after treatment (P < 0.05). The remifentanil+midazolam group had significantly shorter time to awake, extubation time, duration of mechanical ventilation, and length of PICU stay than the midazolam group (P < 0.05). There were no significant differences in PICU cost, incidence of adverse events, and hepatic and renal functions before and after treatment between the two groups (P > 0.05). Both groups showed a significant decrease in fasting blood glucose level after treatment (P < 0.05). Conclusions For children with mechanical ventilation in the PICU, remifentanil+midazolam treatment can rapidly achieve analgesia and sedation, improve the effect of mechanical ventilation, and reduce the dose of sedative compared with midazolam alone, and is well tolerated.
Objective To investigate the short-term clinical outcomes of neonates of secundiparous mothers, and to provide a reference for the clinical practice after the change in birth policy. Methods A cohort study was performed for the parturients and their neonates born in Yongkang Maternal and Child Health Care Hospital in Zhejiang, China between June 2015 and April 2016. According to the parity of the mother, the neonates were divided into primiparous group and secundiparous group. The short-term clinical outcomes of neonates were compared between the two groups. Results A total of 4 091 neonates who met the inclusion criteria were enrolled, and there were 2 023 neonates in the primiparous group and 2 068 in the secundiparous group. In the secundiparous group, most mothers (57.16%) were aged 26-34 years, and 16.49% were aged above 35 years. Compared with the primiparous group, the secundiparous group had a significantly higher rate of births by cesarean section (42.55% vs 25.06%; P < 0.05). The percentages of neonatal respiratory distress syndrome (NRDS; 8.6% vs 3.4%) and transient tachypnea of the newborn (TTN; 7.2% vs 2.6%; P < 0.05) in hospitalized neonates from the secundiparous group were significantly higher than in those from the primiparous group. Conclusions Elderly parturient women are not the major population of secundiparous parturients. The neonates of secundiparous mothers have a higher rate of births by cesarean section, which might be associated with increased percentages of NRDS and TTN in hospitalized neonates from the secundiparous mothers.
Objective To study the gene mutation profile of primary carnitine deficiency (PCD) in neonates, and to provide a theoretical basis for early diagnosis and treatment, genetic counseling, and prenatal diagnosis of PCD. Methods Acylcarnitine profile analysis was performed by tandem mass spectrometry using 34 167 dry blood spots on filter paper. The SLC22A5 gene was sequenced and analyzed in neonates with free carnitine (C0) levels lower than 10 μmol/L as well as their parents. Results In the acylcarnitine profile analysis, a C0 level lower than 10 μmol/L was found in 10 neonates, but C0 level was not reduced in their mothers. The 10 neonates had 10 types of mutations at 20 different sites in the SLC22A5 gene, which included 4 previously unreported mutations:c.976C > T, c.919delG, c.517delC, and c.338G > A. Bioinformatics analysis showed that the four new mutations were associated with a risk of high pathogenicity. Conclusions Tandem mass spectrometry combined with SLC22A5 gene sequencing may be useful for the early diagnosis of PCD. Identification of new mutations enriches the SLC22A5 gene mutation profile.
The patient was a girl aged 3 years and 8 months with normal body length and body weight at birth. The girl had feeding difficulty after birth. Her height, body weight, and head circumference were below the 3rd percentile. She had intellectual disability and an unusual facies manifesting as arched shaggy eyebrows, down-slanting palpebral fissures, and broad nasal bridge, but had no a beaked nose, broad thumbs, or big toes. These clinical manifestations were basically consistent with Rubinstein-Taybi syndrome (RSTS). Gene sequencing identified a heterozygous splice site mutation, c.3779T+1G > T, in the CREBBP gene, which did not exist in her parents. Therefore, a definite diagnosis of RSTS was made. The mutation c.3779T+1G > T had not been reported in the Human Gene Mutation Database and was identified as a novel pathogenic mutation. Then the girl was given rehabilitation training for delayed language and motor development. The girl has been followed up for 3 months in the outpatient department, but the effect of rehabilitation treatment has not been evaluated.
The aim of the study was to provide a descriptive analysis of familial male-limited precocious puberty (FMPP), which is a rare inherited disease caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR). The patient was a ten-month-old boy, presenting with penile enlargement, pubic hair formation, and spontaneous erections. Based on the clinical manifestations and laboratory data, including sexual characteristics, serum testosterone levels, GnRH stimulation test, and bone age, this boy was diagnosed with peripheral precocious puberty. Subsequently the precocious puberty-related genes were analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. Genetic analysis revealed a novel heterozygous missense mutation c.1732G > C (Asp578His) of the LHCGR gene exon11 in the patient, which had never been reported. His parents had no mutations. After combined treatment with aromatase inhibitor letrozole and anti-androgen spironolactone for six months, the patient's symptoms were controlled. The findings in this study expand the mutation spectrum of the LHCGR gene, and provide molecular evidence for the etiologic diagnosis as well as for the genetic counseling and prenatal diagnosis in the family.
Objective To examine serum 25-hydroxyvitamin D levels in children with tic disorders (TD) and to explore the relationship between vitamin D level and TD. Methods One hundred and thirty-two children who were diagnosed with TD between November 2016 and May 2017 were enrolled as the TD group, including 8 cases of Tourette syndrome, 32 cases of chronic TD, and 92 cases of transient TD. One hundred and forty-four healthy children served as the control group. Peripheral venous blood samples were collected from each child. Serum levels of 25-hydroxyvitamin D were measured using HPLC-MS/MS. The categories of vitamin D status based on serum 25-hydroxyvitamin D level included:normal ( > 30 ng/mL), insufficiency (10-30 ng/mL) and deficiency ( < 10 ng/mL). Results Mean serum level of 25-hydroxyvitamin D in the TD group was significantly lower than that in the control group (P < 0.01). The rate of vitamin D insufficiency or deficiency in the TD group was significantly higher than in the control group (P < 0.01). Mean serum level of 25-hydroxyvitamin D in the transient tic group was higher than in the TS group (P < 0.05). Conclusions Vitamin D insufficiency or deficiency might be associated with the development of TD, and the level of serum 25-hydroxyvitamin D might be related to the classification of TD.
The clinical manifestations of five children with paroxysmal kinesigenic dyskinesia (PKD) were retrospectively analyzed and their gene mutations were analyzed by high-throughput sequencing and chromosome microarray. The 5 patients consisted of 4 males and 1 female and the age of onset was 6-9 years. Dyskinesia was induced by sudden turn movement, scare, mental stress, or other factors. These patients were conscious and had abnormal posture of unilateral or bilateral extremities, athetosis, facial muscle twitching, and abnormal body posture. The frequency of onset ranged from 3-5 times a month to 2-7 times a day, with a duration of < 30 seconds every time. Electroencephalography showed no abnormality in these patients. Three patients had a family history of similar disease. The high-throughput sequencing results showed that a heterozygous mutation in the PRRT2 gene, c.649_650insC (p.R217PfsX8), was found in two patients; the mutation c.436C > T (p.P146S) was found in one patient; a splice site mutation, IVS2-1G > A, was found in one patient. The two mutations c.436C > T and IVS2-1G > A had not been reported previously. The chromosome microarray analysis was performed in one patient with negative results of gene detection, and the chromosome 16p11.2 deletion (0.55 Mb) was observed. Low-dose carbamazepine was effective for treatment of the 5 patients. PKD is a rare neurological disease. The detection of the PRRT2 gene by multiple genetic analysis can help the early diagnosis of PKD.
Objective To investigate the significance of flexible bronchoscopy in children with respiratory diseases. Methods A retrospective analysis was performed for the clinical data of 80 children who were hospitalized due to respiratory diseases (including severe pneumonia, Mycoplasma pneumoniae pneumonia with atelectasis/lung consolidation/local emphysema, protracted pneumonia, coughing and wheezing of unknown cause, chronic cough of unknown cause, and laryngeal stridor) and who underwent flexible bronchoscopy/alveolar lavage. Results Bronchoscopy found that all the 80 children had endobronchial inflammation, among whom 28 children had severe airway obstruction by secretion. Twenty-four children had congenital airway dysplasia besides endobronchial inflammation, and three children had bronchial foreign bodies. In the children with coughing and wheezing of unknown cause and laryngeal stridor, some had congenital airway dysplasia or bronchial foreign bodies. Among the 27 children with Mycoplasma pneumoniae pneumonia, 26 had severe airway obstruction/embolization by secretion; 25 children (93%) underwent chest imaging again at 2 weeks after alveolar lavage, and the results showed complete or partial lung recruitment. Among the 80 children who underwent bronchoscopy, 3 had severe hypoxemia during surgery, 1 had epistaxis, 1 had minor bleeding during alveolar lavage, 3 had transient bronchospasm, and 5 had postoperative fever; these children were all improved after symptomatic treatment. Conclusions Flexible bronchoscopy is safe and reliable in children with respiratory diseases. Early alveolar lavage under a flexible bronchoscope is recommended for children with severe/refractory Mycoplasma pneumoniae pneumonia to improve prognosis. Flexible bronchoscopy is recommended for children with recurrent coughing and wheezing and persistent laryngeal stridor, in order to directly observe the throat and airway under an endoscope.
Objective To investigate the association of drug resistance of Mycoplasma pneumoniae (MP) with DNA load and genotypes in children with MP pneumonia. Methods A total of 230 children who were hospitalized and diagnosed with MP pneumonia between January 2012 and December 2016 were enrolled. Throat swabs were collected from the 230 children, and a rapid drug sensitivity assay was used to determine the sensitivity of clinical isolates of MP to nine commonly used antibacterial agents. Quantitative real-time PCR was used to measure MP-DNA load in throat swabs. PCR sequencing was used to determine the genotype of 2063 locus of the MP 23S rRNA V domain. Results Of the 230 children, 86 (37.4%) had genotype A in 2063 locus, 134 (58.3%) had genotype G, 8 (3.5%) had genotype C, and 2 (0.9%) had genotype T. Mutant strains (genotype G+C+T) had a significantly higher MP-DNA load than wild-type strains (genotype A) (P < 0.05). The strains resistant to erythromycin, azithromycin, clarithromycin, and clindamycin had a significantly higher MP-DNA load than non-resistant strains (P < 0.05). MP had a high drug resistance rate to macrolide antibiotics. More than 60% of the cases with resistance to macrolides were found to have A2063G mutations. MP was rarely resistant to quinolones (less than 2%). Conclusions Mutations in 2063 locus of the MP 23S rRNA V domain may result in the resistance of MP to macrolides and the change in DNA load and can be used as a basis for selecting drugs for MP.
Objective To investigate the distribution characteristics of serum specific IgE (sIgE) for inhaled allergens in children with different airway allergic diseases. Methods Fluorescent enzyme-linked immunosorbent assay on the UniCAP250 system was performed to measure serum sIgE for 9 common inhaled allergens in 256 children aged 3-14 years with different airway allergic diseases. According to the clinical diagnosis, these children were divided into rhinitis group (37 children with allergic rhinitis), asthma group (82 children with bronchial asthma), and rhinitis-asthma group (137 children with allergic rhinitis complicated by bronchial asthma). The three groups were compared in terms of the detection rates of 9 inhaled allergens, sensitization level, and number of allergens. Results The detection rate of serum sIgE for inhaled allergens was 57.3% (47/82) in the asthma group, 86.5% (32/37) in the rhinitis group, and 82.5% (113/137) in the rhinitis-asthma group (P < 0.05). The most common allergen in the asthma, rhinitis, and the rhinitis-asthma groups was mould fungi (32.9%, 54.1%, and 48.9% respectively), followed by dust mites (30.5%, 45.9%, and 46.0% respectively), pollen (26.8%, 35.1%, and 32.8% respectively), pets (12.2%, 27.0%, and 18.2% respectively), and cockroach (9.8%, 5.4%, and 5.8% respectively). The rhinitis group and the rhinitis-asthma group had a significantly higher detection rate of mould fungi (mx2) than the asthma group (P < 0.0166). There were no significant differences in the sensitization level of 9 allergens and number of allergens between the three groups. Conclusions In children with either bronchial asthma, allergic rhinitis, or bronchial asthma complicated by allergic rhinitis, the three most common inhaled allergens are mould fungi, dust mites, and pollens. Compared with bronchial asthma, allergic rhinitis may be more closely associated with sensitization by mould fungi. The three common airway allergic diseases have similar distribution characteristics of inhaled allergens.
No abstract available
Objective To analyze the perioperative clinical data of children with congenital heart disease complicated by acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery, and to explore potential factors influencing the prognosis. Methods A retrospective analysis was performed among 118 children with congenital heart disease who developed AKI within 48 hours after CPB surgery. Results In the 118 patients, 18 died after 48 hours of surgery. Compared with the survivors, the dead children had significantly higher incidence of cyanotic disease and Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) scores before surgery; during surgery, the dead children had significantly longer CPB time and aortic cross-clamping time, a significantly higher proportion of patients receiving crystalloid solution for myocardial protection, and a significantly higher mean blood glucose level. Within 48 hours after surgery, the dead children had significantly higher positive inotropic drug scores, significantly higher creatinine values, a significantly higher incidence of stage 3 AKI, a significantly higher proportion of patients receiving renal replacement the, and significantly higher usage of blood products (P < 0.05). The mortality rate of the patients increased with increased intraoperative blood glucose levels (P < 0.05). Patients with intraoperative blood glucose levels > 8.3 mmol/L had a significantly lower postoperative cumulative survival rate and a significantly shorter mean survival time than those with blood glucose levels ≤ 8.3 mmol/L (P < 0.05). Conclusions Intraoperative blood glucose levels are associated with the prognosis in children with congenital heart disease complicated by AKI after CPB surgery. Maintaining good intraoperative blood glucose control can improve the prognosis of the children.
Objective To explore the effects of rat bone mesenchymal stem cell (BMSC) transplantation on retinal neovascularization, and to observe the changes of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factors (VEGF) in rats with oxygen-induced retinopathy (OIR). Methods Seventy-two seven-day-old Sprague-Dawley rats were randomly divided into three groups:normal control (CON), model (OIR) and BMSC transplantation. In the BMSC transplantation group, BMSCs were transplanted 5 days after oxygen conditioning. The phosphate buffered saline of the same volume was injected in the CON and OIR groups. The OIR model was prerpared according to the classic hyperoxygen method. At seven days after transplantation, retinal neovascularization was examined by retinal flat-mount staining and hematoxylin eosin (HE) staining. The expression of HIF-1α and VEGF proteins was examined by immunohistochemistry staining and Western blot analysis. Results The retinal flat-mount staining results showed that the vessels were well organized in the CON group, but the vessels were irregularly organized, and lots of nonperfusion areas were observed in the OIR group. The large vessels were a bit circuitous, the retinal vessels were relatively organized, and less nonperfusion areas were noted in the BMSC transplantation group. The HE staining results showed that many neovessels and preretinal neovascular (pre-RNC) cells were observed on the internal limiting membrane in the OIR group. There were less pre-RNC cells in the BMSC transplantation group compared with the OIR group (P < 0.01). The immunohistochemistry analysis showed that more HIF-1α+ and VEGF+ cells were observed in the OIR group compared with the CON group, and less HIF-1α+ and VEGF+ cells were observed in the BMSC transplantation group compared with OIR group (P < 0.05). The Western blot analysis showed the expression of HIF-1α and VEGF proteins in the OIR group was significantly higher than that in the CON group. The expression of HIF-1α and VEGF proteins in the BMSC transplantation group was lower than that in the OIR group (P < 0.01). Conclusions BMSC transplantation therapy could alleviate retinal neovascularization in OIR rats, and its mechanisms might be associated with the inhibition of the expression of HIF-1α and VEGF proteins.
Objective To investigate the effect of oridonin on the human acute lymphocytic leukemia cell line Jurkat and its mechanism. Methods Jurkat cells were cultured in vitro and treated with various concentrations (0, 1.25, 2.5, 5, and 10 μmol/L) of oridonin for different lengths of time (24, 48, and 72 hours). The proliferation of Jurkat cells was analyzed by MTT assay. The changes in nuclear morphology were evaluated by fluorescence microscopy at 12 hours after treatment with various concentrations of oridonin. The expression levels of Brg1, P53, and C-myc were determined by semi-quantitative Western blot in Jurkat cells treated with various concentrations of oridonin for 24 hours or 5 μmol/L oridonin for various lengths of time (0, 2, 6, 12, and 24 hours). The expression levels of P53 and C-myc and proliferation of Jurkat cells were evaluated after Brg1 expression was knocked down by Brg1-specific siRNA. Results Compared with the control group, the proliferation of oridonin-treated Jurkat cells was significantly inhibited in a concentration-and time-dependent manner (P < 0.05). According to the florescence microscopic analysis, oridonin treatment led to nuclear pyknosis in Jurkat cells. Compared with the control group, Jurkat cells treated with 5 μmol/L oridonin had reduced expression of Brg1 and C-myc but elevated expression of P53. Brg1 knock-down led to a significant reduction in proliferation of Jurkat cells (P < 0.05), up-regulated expression of P53, and down-regulated expression of C-myc. Conclusions Oridonin can inhibit the proliferation of Jurkat cells, probably via the Brg1 signaling pathway.
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a subtype of B-lineage ALL (B-ALL) that displays a gene expression profile (GEP) similar to Philadelphia chromosome-positive ALL (Ph+ ALL). It has a diverse range of genetic alterations that activate cytokine receptor genes and kinase signaling pathways, frequently accompanied by abnormal transcription factors related to lymphatic development. Children with Ph-like ALL account for 15% of children with high-risk B-ALL. It has adverse clinical features and a poor prognosis. Tyrosine kinase inhibitors combined with chemotherapy can significantly improve the prognosis of children with Ph+ ALL, suggesting that targeted therapy based on the molecular cytogenetic abnormalities of Ph-like ALL has good research prospects. This paper expounds the genetic alterations, pathogenesis, clinical features, diagnostic measures, and potential therapeutic approaches of Ph-like childhood ALL based on recent research progress in Ph-like ALL.
Nowadays, the 5-year survival rate of childhood cancer patients can be more than 80%, but some patients with relapse and refractory cancers have shown no good response to traditional strategies. Chimeric antigen receptor engineered T (CAR-T) cell therapy is promising for these patients. CAR-T cells recognize the tumor-associated antigens in a non-major histocompatibility complex-restricted manner, so their anti-tumor ability is enhanced. There are four generations of CAR-T cells now. The complete remission rate of pediatric patients with relapse and refractory acute lymphoblastic leukemia can be as high as 90% when treated with CD19-targeting CAR-T cells. Furthermore, CAR-T cell therapy can also be used to bridge to transplantation and donor CAR-T cell infusion can be a strategy to prevent relapse after hematopoietic stem cell transplantation. As to solid tumors, only patients with neuroblastoma present good response to the GD2-targeting CAR-T cell therapy. The toxic or side effects of CAR-T cell therapy include cytokine release syndrome, off-tumor effect, tumor lysis syndrome, and insertion mutation. Although the CD19-targeting CAR-T cell therapy for childhood cancer can result in a high remission rate, the relapse rate is high, including CD19+ and CD19- relapse. The mechanisms for relapse merit further investigation.
