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Objective:To investigate the clinical characteristics, pathogen distribution and risk factors of late-onset sepsis (LOS) in very low birth weight infants (VLBWI).Methods:In this retrospective case-control study, 107 VLBWIs diagnosed with LOS and hospitalized in Fujian Provincial Maternity and Children's Hospital from January 1, 2010 to December 31, 2015 were enrolled as LOS group. Another 107 VLBWIs without infection were assigned as control group with an allocation ratio of 1 to 1. The clinical data between groups were compared using two-independent sample t-test, Chi-square test, sum-rank test and univariate analysis of variance, and multivariate logistic regression was used to analyze the risk factors of LOS. Results:The incidence of LOS in VLBWI was 8.6% (107/1 239). Among the 107 cases with LOS, 87 recovered with a cure rate of 81.3%. Various clinical presentations were observed, and the most common included lethargy (83/107, 77.6%), abdominal distention (77/107, 72.0%) and dyspnea (76/107, 71.0%). Increased C-reactive protein (CRP) level was the most common laboratory markers (82/107, 76.6%). The blood cultures were positive in 45 (42.1%) cases and the dominant pathogen was Gram-negative bacteria (32/45, 71.1%), especially Klebsiella. The logistic regression analysis showed that mechanical ventilation ( OR=21.181, 95% CI: 1.542-290.948, P=0.022), feeding intolerance ( OR=12.480, 95% CI: 2.602-59.856, P=0.002), combined application of antibiotics before LOS occurs ( OR=22.457, 95% CI: 3.933-128.237, P<0.001), duration of antibiotic treatment before LOS occurs ( OR=1.388, 95% CI: 1.158-1.663, P<0.001) were the independent risk factors of LOS for VLBWI. Conclusions:The clinical presentation of LOS in VLBWI are diverse and non-specific. Increased CRP level is a sensitive laboratory marker. The main pathogen is Gram-negative bacteria. LOS are more prone to occur in VLBWI with mechanical ventilation, feeding intolerance, combined application of antibiotics or long duration of antibiotic treatment.
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Objective To investigate the clinical and molecular genetic features of neonatal congenital lipoid adrenal hyperplasia (CLAH) caused by mutations in steroidogenic acute regulatory protein (StAR) encoding gene.Methods This study retrospectively analyzed the clinical data of a CLAH neonate admitted to Fujian Provincial Matemity and Children's Hospital,Affiliated Hospital of Fujian Medical University in April 2017.StAR gene was analyzed using high-throughput sequencing and Sanger sequencing.Relevant literature retrieved from databases including China National Knowledge Infrastructure (CNKI),Wanfang and PubMed were reviewed,and the reported cases with relatively complete clinical data and results of serum hormone test and StAR gene mutation analysis were collected.Results The index patient presented with hyperpigrnentation and growth retardation soon after birth.Laboratory tests revealed hyponatremia,hyperkalemia,increased serum adrenocorticotrophic hormone (263.4 pmol/L) and decreased 17-hydroxyprogesterone (0.16 ng/ml),dehydroepiandrosterone (＜0.95 μmol/L),androstenedione (＜1.0 nmol/L),testosterone (＜0.025 ng/ml),progesterone (0.02 ng/ml) and cortisol (1.6 μ g/ml).High-throughput sequencing showed that the patient carried a compound heterozygous mutation of p.Thr240fs in exon 6 and p.Gln258X in exon 7,inherited from the father and mother,respectively.Sanger sequencing confirmed the diagnosis of CLAH caused by StAR gene mutation.After steroid replacement therapy,the patient's symptoms resolved and the concentrations of electrolytes returned to normal.The neonate was followed up to two years of age and no abnormality was found in physical or neurological development.Two Chinese and 11 English publications were retrieved and altogether 96 cases of neonatal CLAH,including the index one,were reviewed and 42 of them had detailed clinical data.The most common clinical manifestations were skin pigmentation (85.7％,36/42).Other manifestations included vomiting (35.7％,15/42) and growth retardation (14.3％,6/42).All patients with physical examination records had female external genitalia (100.0％,35/35).The common laboratory abnormalities included hyponatremia (95.2％,40/42),hyperkalemia (88.1％,37/42),elevated serum adrenocorticotrophic hormone (100.0％,37/37) and decreased 17-hydroxyprogesterone (90.5％,19/21),cortisol (86.2％,25/29),testosterone (9/10) and dehydroepiandrosterone (14/14).p.Gln258X was the most common StAR gene mutation in neonates in Eastern Asia,including China.Most cases had a good prognosis after appropriate steroid replacement.Conclusions CLAH should be considered for neonates with adrenocortical hypofunction,especially with female phenotypes and low 17-hydroxyprogesterone.Karyotyping and StAR gene analysis may be helpful in diagnosis.Timely and appropriate treatment could improve the prognosis.
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Objective@#To investigate the clinical and molecular genetic features of neonatal congenital lipoid adrenal hyperplasia (CLAH) caused by mutations in steroidogenic acute regulatory protein (StAR) encoding gene.@*Methods@#This study retrospectively analyzed the clinical data of a CLAH neonate admitted to Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University in April 2017. StAR gene was analyzed using high-throughput sequencing and Sanger sequencing. Relevant literature retrieved from databases including China National Knowledge Infrastructure (CNKI), Wanfang and PubMed were reviewed, and the reported cases with relatively complete clinical data and results of serum hormone test and StAR gene mutation analysis were collected.@*Results@#The index patient presented with hyperpigmentation and growth retardation soon after birth. Laboratory tests revealed hyponatremia, hyperkalemia, increased serum adrenocorticotrophic hormone (263.4 pmol/L) and decreased 17-hydroxyprogesterone (0.16 ng/ml), dehydroepiandrosterone (<0.95 μmol/L), androstenedione (<1.0 nmol/L), testosterone (<0.025 ng/ml), progesterone (0.02 ng/ml) and cortisol (1.6 μg/ml). High-throughput sequencing showed that the patient carried a compound heterozygous mutation of p.Thr240fs in exon 6 and p.Gln258X in exon 7, inherited from the father and mother, respectively. Sanger sequencing confirmed the diagnosis of CLAH caused by StAR gene mutation. After steroid replacement therapy, the patient's symptoms resolved and the concentrations of electrolytes returned to normal. The neonate was followed up to two years of age and no abnormality was found in physical or neurological development. Two Chinese and 11 English publications were retrieved and altogether 96 cases of neonatal CLAH, including the index one, were reviewed and 42 of them had detailed clinical data. The most common clinical manifestations were skin pigmentation (85.7%, 36/42). Other manifestations included vomiting (35.7%, 15/42) and growth retardation (14.3%, 6/42). All patients with physical examination records had female external genitalia (100.0%, 35/35). The common laboratory abnormalities included hyponatremia (95.2%, 40/42), hyperkalemia (88.1%, 37/42), elevated serum adrenocorticotrophic hormone (100.0%, 37/37) and decreased 17-hydroxyprogesterone (90.5%, 19/21), cortisol (86.2%, 25/29), testosterone (9/10) and dehydroepiandrosterone (14/14). p.Gln258X was the most common StAR gene mutation in neonates in Eastern Asia, including China. Most cases had a good prognosis after appropriate steroid replacement.@*Conclusions@#CLAH should be considered for neonates with adrenocortical hypofunction, especially with female phenotypes and low 17-hydroxyprogesterone. Karyotyping and StAR gene analysis may be helpful in diagnosis. Timely and appropriate treatment could improve the prognosis.
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Objective To summarize the clinical features of neonatal lupus erythematosus (NLE) and to have a better clinical understanding. Methods We retrospectively analyzed the clinical data of 13 patients with NLE who were hospitalized in Fujian Provincial Maternity and Children's Hospital from September 2010 to September 2017. The pathogenesis, clinical manifestations, laboratory examinition, management and long term outcomes of these babies were summarized, and the relevant literatures were also reviewed. Descriptive statistical analysis was performed. ResuLts The 13 NLE cases included eight boys and five girls. Among them, skin lesions, cardiac impairment, hematological problems, hepatobiliary system damage, central nervous system involvement and renal function damage occurred in eight, seven (six cases were atrioventricular block), seven, three, one and one case, respectively. Antinuclear antibodies and anti-Sjogren's syndrome antigen A antibodies were positive in all neonates, anti-Sjogren's syndrome antigen B antibodies were positive in 11, and anti-double-stranded DNA antibodies were positive in two cases. Among the 13 mothers, three were diagnosed with Sjogren's syndrome and two had systemic lupus erythematosus(SLE) before pregnancy, two were diagnosed with Sjogren's syndrome and one developed SLE during pregnancy. Eight babies with skin lesions were asked to avoid light and the skin rash all gradually receded within 1-6 months after birth. Five cases with thrombocytopenia were treated with intravenous immunoglobulin and one anemic baby received erythrocyte transfusion. Within 2 to 3 months, the impaired blood system in these babies were back to normal. For the three babies with abnormal liver functions, hepatic protectants and jaundice relieving agents were given, and 2 to 6 months later they recovered. The 13 patients were followed up for five months to seven years, among which, seven improved with normal growth and development; five still had grade Ⅲ atrioventricular block; one installed an atrial pacemaker at 11 months. Three mothers who were asymptomatic during pregnancy were found to have autoimmune diseases after their babies were diagnosed with NLE, including one case of Sjogren's syndrome and two of SLE. ConcLusions NLE is mainly characterized by skin lesions and congenital heart block, while liver, blood system, central nervous system and other organs may also be involved. For high-risk mothers and babies, timely autoantibody screening and relevant examinations are suggested for early diagnosis and interventions. In addition, long term follow-up is required for affected cases.
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Objective To evaluate the effects of the quality-improving program on reducing the bloodstream infection of preterm infants in NICU.The program included emphasizing hand hygiene,strictly controlling the use of antibiotics and following the extubation indications of peripherally inserted central catheter (PICC).Method From October 2016 to March 2017,preterm infants admitted to NICU after the implementation of quality improvement program were assigned into the intervention group,and the infants admitted from April 2016 to September 2016 without the program were in the control group.The x2 test and t test were used to analyse the effects of the program,the rate of bloodstream infection and related complications.Result A total of 432 cases were enrolled in this study.Among them,221 cases were in the intervention group and 211 cases the control group.The rate of hand hygiene in the intervention group was significantly higher and the duration of antibiotic use per 1 000 hospitalization days and the average days of retaining the PICC were significantly shorter than the control group (P ＜ 0.001).The incidence of bloodstream infection in the intervention group was lower than the control group (5.9％ vs.11.4％,P =0.047),and the duration of non-invasive ventilation,parenteral nutrition,average hospitalization days,and the incidence of stage 11 and above necrotizing enterocolitis were lower than the control group (P ＜ 0.05).Conclusion The evidence-based quality improvement program has positive effects on reducing the bloodstream infections and related complications of preterm infants in NICU.
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Objective To explore the efficacy and safety of high-dose second-generation fat emulsion usage on the very low birth weight premature infants.Methods A total of 88 premature infants with very low birth weight (VLBW) in Neonatal Intensive Care Unit (NICU)of Fujian Provincial Maternity and Children Hospital,Affiliated Hospital of Fujian Medical University from December 2013 to December 2014 were randomly divided into experimental group and control group,with 44 cases in each group according to the table of random number.The experimental group received intravenous nutrition with 200 g/L second-generation fat emulsion within 24 hours after birth,the initial dose was 2.0 g/(kg · d) with an increase of (0.5-1.0) g/(kg · d) daily,the maximum dose was 3.5 g/(kg · d);the control group received intravenous nutrition with 200 g/L second-generation fat emulsion 24 hours later after birth,the initial dose was 0.5 g/(kg · d) with an increase of 0.5 g/(kg · d) daily,the maximum dose was 3.5 g/(kg · d).The other intravenous nutrition methods were same.The general conditions at birth,blood biochemical parameters,growth parameters and complications were compared between the 2 groups.Results The mean value of intravenous nutrition duration,length of stay,the glucose infusion rates of postnatal days 6 and 7,the serum triglyceride levels of postnatal days 7,chest circumference of the fourth weeks,the incidence of the low triiodothyronine(T3) syndrome and parenteral nutrition associated cholestasis(PNAC) were (22.27 ± 7.17) d,(37.75 ± 12.28) d,(8.10 ± 0.92) mg/(kg · min),(8.49 ± 1.06) mg/(kg · min),0.18(0.03-0.59) mmol/L and (27.21 ± 1.62) cm in the experimental group respectively,but (27.36 ± 11.37) d,(44.36 ± 16.45) d,(7.98 ±0.79) mg/(kg · min),(8.22 ±0.76) mg/(kg · min),0.28 (0.07-0.99) mmol/L and (26.56 ± 0.96) cm in the control group,respectively,and the differences were statistically significant between the 2 groups (t =2.512,5.403,4.314,9.705,696.500,6.668,all P ＜ 0.05).The incidence of the T3 syndrome and parenteral nutrition associated cholestasis (PNAC) in the experimental group was 25.0％ (11/44 cases) and 0(0/44 cases),respectively,which were significantly lower than those in the control group[81.8％ (36/44 cases)and 9.1％ (4/44 cases)],and the differences were statistically significant between the 2 groups (x2 =28.542,5.736,all P ＜ 0.05).The 2 groups had no significant difference in the incidence rates of other complications such as necrotizing enterocolitis,infection,retinopathy of prematurity,bronchopulmonary dysplasia,and the duration of oxygen therapy and mechanical ventilation(all P ＞ 0.05).Conclusions The high-dose second-generation fat emulsion usage [the initial dose 2.0 g/(kg · d)] in VLBW infants is safe and well tolerated.Advisable parenteral nutrition support strategy can promote growth of VLBW infants,shorten the intravenous nutrition duration and length of stay,reduce the incidence of the low T3 syndrome and PNAC,which has no influence on the incidence rates of other complications.
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Objective To assess the association of single nucleotide polymorphisms (SNPs)of biliverdin reductase A (BLVRA) with neonatal hyperbilirubinemia from Fujian area.Methods A total of 286 patients with neonatal hyperbilirubinemia and 250 healthy controls were enrolled.Genotypes of 5 SNPs within BLVRA gene including rs699512,rs1802846,rs7738,rs1637530 and rs2302032 were determined with matrix-assisted laser desorption ionization/time of flight mass spectrometer.The frequencies of genotype,allele,haplotype and their differentiations were analyzed.Results All 5 SNPs had conformed to Hardy-Weinberg equilibrium (all P ＞ 0.05).rs699512 and rs1637530 showed a significant difference between the 2 groups in both allelic and genotypic frequencies (all P ＜ 0.05),but no significant differences were found in the other SNPs(all P ＞ O.05).In recessive model,the frequency of rs699512 GG genotype of patients was significantly lower than that of the healthy control group(OR =0.494,95％ CI:0.276-0.886,P =0.018),while in dominant model,the frequencies of rs699512 GG + AG and rs1637530 TT + CT genotype of patients were significantly lower than that of the healthy control group(OR =0.678,0.627;95％ CI:0.482-0.954,0.444-0.885;P =0.026,0.008).Based on linkage disequilibrium analysis and haplotype construction,rs1637530,rs2302032,rs699512 and rs1802846 locus in the same area.Based on haplotype CGAT,TGGT,CTAT and CGGT had significant differences between the 2 groups (all P ＜ 0.05),and could reduce the risk of high blood bilirubin (OR =0.588,0.687,0.501;95％ CI:0.434-0.797,0.496-0.952,0.250-1.004).Conclusions rs699512 and rs1637530 may be associated with neonatal hyperbilirubinemia,A allele in rs699512 and C allele in rs1637530 may be associated with significantly increased risk of neonatal hyperbilirubinemia.
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Objective To investigate the prevalence of DUOX2 mutations in Chinese patients with congenital hypothyroidism (CH) and to discuss the inheritance pattern of DUOX2 gene.Methods Blood samples were collected from 91 CH children and their genomic DNA was extracted from peripheral blood leukocytes.All exons and exon-intron boundaries of DUOX2 were analyzed by target next-generation sequencing and family trios was established to study the inheritance pattern of DUOX2 gene.Results Fifty-four out of 91 children with CH carried DUOX2 mutation, with a prevalence of 59.34%.Of the 54 CH children, 36 carried DUOX2 biallelic mutations.In all 12 family trios with probands carrying biallelic DUOX2 mutations, the parents carried heterozygous DUOX2 mutations while still showing normal thyroid function, suggesting that CH caused by DUOX2 mutations is inherited in an autosomal recessive manner.Conclusion DUOX2 gene is one of the most frequently mutated genes in Chinese CH patients and its inheritance pattern is an autosomal recessive one.
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Objective To establish a simple, reliable and reproducible animal model of neonatal hypoxic-ischemic encephalopathy (HIE) with similar clinical pathological process to neonates.Methods Seven days after birth, 180 Sprague-Dawley (SD) rats were randomly divided into six groups: blank control group, experimental control group and four hypoxia groups (8, 10, 12 and 14 min hypoxia groups). Those in the experimental groups were locally anesthetized with 5％ lidocaine to separate their tracheas through blunt dissection, followed by tracheal clamping with vascular clamp for 8, 10, 12 and 14 min, respectively. Rats in the experimental control group were only treated with blunt dissection of trachea. No intervention was given to the blank control group. Due to significant reduction in rat survival rate after 14 min of hypoxia, no further morphological or behavioral examination was performed in this group. Rat brain tissue sections were stained with hematoxylin-eosin (HE) 12 h after modeling. Three days after modeling, the rat brain was weighted and the apoptosis of neural cells was detected with terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick end labeling (TUNEL). Morris water maze was used to screen cognitive impairment in these rats at the age of two months. One-way analysis of variance was used for statistical analysis. SNK test and Dunnett 's T3 test were performed to compare homogeneous and non-homogeneous data between groups.Results Systemic cyanosis, loss of consciousness, paled body, urinary and fecal incontinence, twitching of the limbs and tail and other abnormal behavior were induced by hypoxia. Ischemic necrosis, bleeding, nucleus shrinkage in a large number of neurons and hyperchromatic nuclei were observed in the 8, 10 and 12 min hypoxia groups. Three days after modeling, brain weights of rats in the 8, 10 and 12 min hypoxia groups were lower than those of the blank control group and experimental control group [(1.16±0.07), (1.04±0.06), (0.97±0.12), (1.31±0.06) and (1.28± 0.09) g,F=36.437,P<0.001]. However, the numbers of apoptotic cortical [(22.83±4.52), (30.25±3.02), (39.18±5.04), (7.96±2.24) and (8.86±2.49)/400 scope field,F=164.532,P<0.001]and hippocampal CA3 neurons of that three hypoxia groups were higher than those of the two control groups [(14.63±2.26), (20.25±3.02), (24.81±1.98), (4.75±2.66) and (6.67±1.78)/400 scope field,F=141.026,P<0.001]. At the age of two months, rats in the 8, 10 and 12 min hypoxia groups had longer escape latency [(17.99±6.48), (23.07±9.90), (38.94±32.46), (14.37±6.06) and (12.78±7.21) s,F=26.912,P<0.001]and fewer times of platform crossings than those in the control group and experimental control group [(5.00±1.41), (4.90±1.29), (3.75±1.83), (7.57±1.16) and (7.14±1.15) times,F=14.336,P<0.001].Conclusions Pathological changes in brain tissues and behaviors of rats after modeling are in line with the characteristics of classic animal model of HIE and similar to the clinical pathology and physiology of HIE, and this could be a new, simple, reliable and reproducible animal model of HIE, being capable of controlling the duration of hypoxia accurately.
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Objective To study the levels of interleukin-6 (IL-6) and C-reactive protein(CRP) in umbilical cord serum of the newborns with premature rupture of membrane(PROM)and to explore the value of IL-6 and CRP in the diagnosis of early onset neonatal sepsis (EONS).Method A total of 187 term newborns with PROM ＞ 12 h who were born normal vaginally in our Hospital from April 2015 to December 2015 were enrolled in this study as the PROM group and another 50 term infants without PROM and infection as the control group.The levels of IL-6 and CRP in umbilical cord serum were quantified by ELISA,the results of which were compared between groups.Receiver operating characteristics (ROC) curves were drawn to find out the cut-off value of IL-6 and CRP for the diagnosis of EONS.Result The levels of IL-6 and CRP in umbilical cord serum in the PROM group were significantly higher than those in the control group [IL-6 20.3 (9.5,35.8) pg/ml vs.9.3 (6.9,27.5) pg/ml,CRP 0.42 (0.25,0.78) mg/L vs.0.33 (0.18,0.45) mg/L,P ＜ 0.05].The levels of IL-6 and CRP in the newborns whose mother had chorioamnionitis were significantly higher than those in the newborns whose mother was without chorioamnionitis [IL-6 62.5 (35.2,92.7) pg/ml vs.10.8 (9.3,33.4) pg/ml,CRP 0.86 (0.44,1.95) mg/L vs.0.35 (0.20,0.62) mg/L,P ＜0.05].The levels of IL-6 and CRP in the infants with PROM≥18 h was significantly higher than those in the infants with PROM ＜ 18 h [IL-6 32.1 (9.9,42.2) pg/ml vs.10.7 (9.2,32.6) pg/ml,CRP 0.44(0.29,0.86) mg/L vs.0.35 (0.23,0.61) mg/L,P ＜ 0.05].The levels of IL-6 and CRP in the neonates with EONS was significantly higher than those in the neonates without EONS [IL-6 92.0 (58.3,161.0) pg/ml vs.20.0(9.4,35.2)pg/ml,CRP 1.94(0.47,2.73) mg/L vs.0.38(0.24,0.67) mg/L,P ＜ 0.05].ROC curve analysis showed that the cut-off value of IL-6 and CRP for the diagnosis of EONS were 81.lpg/ml (sensitivity 76.5％,specificity 90.6％) and 1.88mg/L (sensitivity 64.7％,specificity 89.4％).With the combination of IL-6 and CRP levels,the sensitivity was 88.2％ and the specificity was 84.1％ for the diagnosis of EONS.Conclusion To measure the IL-6 and CRP levels in umbilical cord serum is helpful for the early diagnosis of EONS,and the combined detection of the 2 items may improve the sensitivity of diagnosis.
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Objective To explore the effect of exogenous recombinant human erythropoietin (rhEPO) on neuronal apoptosis in neonatal rats after hyperoxia brain injury.Methods Thirty neonatal Wistar rats were randomly divided into 3 groups by random number table method:rhEPO treatment + 800 mL/L hyperoxia group (group A),9 g/L saline +800 mL/L hyperoxia group (group B),9 g/L saline + air group (group C).Group A was given subcutaneous injection of rhEPO 1 000 IU/kg for 5 days.Group B and group C received the same dose of 9 g/L saline.Group A and group B were continuously exposed to atmospheric pressure hyperoxia model cabin to maintain the oxygen concentration in the container (800 ± 30) mL/L for 5 days.During the course of the experiment,the general situation and weight changes in rats were observed.After 5 d,all rats were sacrificed and brain tissues were taken.Neuronal apoptosis in hippocampal structural region of the newborn rats was observed by terminal deoxynucleotidyl transferase dUTP nick and labeling(TUNEL) staining.Immunohistochemical method was used to detect the expression of 5-lipoxygenase in hippocampal structural region of newborn rats.Results The weight gain and brain weight of group B were lower than those of group C,the weight gain and brain weight of group A were higher than those of group B,and the differences were statistically significant(F =11.179,8.140,all P ＜ 0.05).In group A and group B were found that the neuronal nucleus of the hippocampal neurons was partially contracted,deeply dyed,and the neuronal arrangement was loose,even with local neuron deletions and focal necrosis,but in group A neuron density was higher with less necrosis than that in group B.The neuronal cells in hippocampal structural region were neat and intact in group C.The number of TUNEL positive cells in hippocampal structural region of group B[(6.20 ± 1.93) number/high power field] was significantly higher than that in group C [(1.80 ± 0.79) number/high power field],the number of TUNEL positive cells in hippocampal structural region of group A [(4.20 ± 1.32) number/high power field] was significantly lower than that in group B,and the difference was statistically significant (F =23.912,P ＜ 0.05).The number of 5-lipoxygenase positive cells in group B [(6.90 ± 1.29) number/high power field] was significantly higher than that in group C [(1.00 ± 0.67) number/high power field],the number of 5-lipoxygenase positive cells in group A [(5.60 ± 0.97)number/high power field] was significantly lower than that in group B,and the difference was statistically significant (F =95.044,P ＜ 0.05).Conclusion rhEPO has a protective effect on neonatal rats with hyperoxia brain injury,and alleviates brain cell apoptosis caused by hyperoxia brain injury,which may interfere with the 5-lipoxygenase pathway.
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Objective To evaluate the role of ibuprofen and hydrocortisone in early treatment of patent ductus arteriosus ( PDA ) in premature infants with low cortisol level . Method A prospective randomized controlled trial on 144 very low birth weight infants in the Hospital within 24 hours after birth with gestational age of 28~32 weeks and birth weight of 1000~1499 grams,who had asymptomatic PDA diagnosed by echocardiography , introducing early administration of drugs including ibuprofen and /or hydrocortisone within the first 24 ~48 hours after birth.According to the baseline of serum cortisol level measured prior to the administration of drugs , the preterm were assigned into two groups .The low cortisol level group ( the cortisol level <150μg/L) were further subdivided into four groups each being allocated to hydrocortisone or ibuprofen or both of hydrocortisone and ibuprofen combined or placebo treatment .The high cortisol level group ( the cortisol level≥150μg/L) were allocated to either ibuprofen or placebo treatment in randomization.Diameter of ductus arteriosus and cortisol value were measured again after treatment , and the follow-ups were undertaken till discharge .All data was collected and analyzed by statistical software .Result A total of 91 cases were in low cortisol level group ( 22 cases of hydrocortisone , 23 cases of ibuprofen , 21 cases of both hydrocortisone and ibuprofen , and 25 cases of placebo ) and 53 cases in high cortisol level group (26 cases of placebo and 27 cases of Ibuprofen ).Low cortisol level group , combined therapy , closure of the ductus at a rate of 81.0%, was higher than other methods of therapy ( P<0.05);high cortisol level group, the ductus arteriosus closed in 20 patients of ibuprofen therapy ( 74.1%) and in 13 patients of placebo treatment (50.0%) (P<0.05).Early treatment did not significantly increase the drug adverse effects, including impaired renal function , gastrointestinal bleeding , hyperglycemia and others. After comparisons between laboratory changes in early targeted groups and non-early targeted groups after treatment, findings were as follows: decrease in the incidence of apnea , myocardial damage , feeding intolerance , intraventricular hemorrhage and reduce the duration of phototherapy .Conclusion This trial proved the efficacy and safety of early therapy with ibuprofen and hydrocortisone for closure of ductus arteriosus in premature infants with low cortisol level and the decreasing incidence of complications due to PDA without increasing the risk of adverse effects .
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Objective@#To investigate the incidence and pathogen distribution of ventilator-associated pneumonia (VAP) among preterm infants admitted to level Ⅲ neonatal intensive care units (NICU) in China.@*Method@#A prospective study was conducted in 25 level Ⅲ NICU, enrolling all preterm infants <34 weeks gestational age admitted to the participating NICU within the first 7 days of life from May 2015 to April 2016. Chi-square test, t test and Mann-Whitney U test were used for statistical analysis.@*Result@#A total of 7 918 patients were enrolled, within whom 4 623(58.4%) were males. The birth weight was (1 639±415) g and the gestational age was (31.4±2.0) weeks; 4 654(58.8%) infants required non-invasive mechanical ventilation and 2 154(27.2%) required intubation. Of all the mechanically ventilated patients, VAP occurred in 95 patients. The overall VAP rate was 7.0 episodes per 1 000 ventilator days, varying from 0 to 34.4 episodes per 1 000 ventilator days in different centers. The incidence of VAP was 9.6 and 6.0 per 1 000 ventilator days in children′s hospitals and maternity-infant hospitals respectively, without significant differences (t=1.002, P=0.327). Gram-negative bacilli (76 strains, 91.6%) were the primary VAP microorganisms, mainly Acinetobacter baumannii (24 strains, 28.9%), Klebsiella pneumonia (23 strains, 27.7%), and Pseudomonas aeruginosa (10 strains, 12.0%).@*Conclusion@#The incidence of VAP in China is similar to that in developed counties, with substantial variability in different NICU settings. More efforts are needed to monitor and evaluate the preventable factors associated with VAP and conduct interventions that could effectively reduce the occurrence of VAP.
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Objective@#To establish a simple, reliable and reproducible animal model of neonatal hypoxic-ischemic encephalopathy (HIE) with similar clinical pathological process to neonates.@*Methods@#Seven days after birth, 180 Sprague-Dawley (SD) rats were randomly divided into six groups: blank control group, experimental control group and four hypoxia groups (8, 10, 12 and 14 min hypoxia groups). Those in the experimental groups were locally anesthetized with 5% lidocaine to separate their tracheas through blunt dissection, followed by tracheal clamping with vascular clamp for 8, 10, 12 and 14 min, respectively. Rats in the experimental control group were only treated with blunt dissection of trachea. No intervention was given to the blank control group. Due to significant reduction in rat survival rate after 14 min of hypoxia, no further morphological or behavioral examination was performed in this group. Rat brain tissue sections were stained with hematoxylin-eosin (HE) 12 h after modeling. Three days after modeling, the rat brain was weighted and the apoptosis of neural cells was detected with terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick end labeling (TUNEL). Morris water maze was used to screen cognitive impairment in these rats at the age of two months. One-way analysis of variance was used for statistical analysis. SNK test and Dunnett 's T3 test were performed to compare homogeneous and non-homogeneous data between groups.@*Results@#Systemic cyanosis, loss of consciousness, paled body, urinary and fecal incontinence, twitching of the limbs and tail and other abnormal behavior were induced by hypoxia. Ischemic necrosis, bleeding, nucleus shrinkage in a large number of neurons and hyperchromatic nuclei were observed in the 8, 10 and 12 min hypoxia groups. Three days after modeling, brain weights of rats in the 8, 10 and 12 min hypoxia groups were lower than those of the blank control group and experimental control group [(1.16±0.07), (1.04±0.06), (0.97±0.12), (1.31±0.06) and (1.28±0.09) g, F=36.437, P<0.001]. However, the numbers of apoptotic cortical [(22.83±4.52), (30.25±3.02), (39.18±5.04), (7.96±2.24) and (8.86±2.49)/400 scope field, F=164.532, P<0.001] and hippocampal CA3 neurons of that three hypoxia groups were higher than those of the two control groups [(14.63±2.26), (20.25±3.02), (24.81±1.98), (4.75±2.66) and (6.67±1.78)/400 scope field, F=141.026, P<0.001]. At the age of two months, rats in the 8, 10 and 12 min hypoxia groups had longer escape latency [(17.99±6.48), (23.07±9.90), (38.94±32.46), (14.37±6.06) and (12.78±7.21) s, F=26.912, P<0.001] and fewer times of platform crossings than those in the control group and experimental control group [(5.00±1.41), (4.90±1.29), (3.75±1.83), (7.57±1.16) and (7.14±1.15) times, F=14.336, P<0.001].@*Conclusions@#Pathological changes in brain tissues and behaviors of rats after modeling are in line with the characteristics of classic animal model of HIE and similar to the clinical pathology and physiology of HIE, and this could be a new, simple, reliable and reproducible animal model of HIE, being capable of controlling the duration of hypoxia accurately.
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Objective To study the clinical characteristics of inherited metabolic disease(IMD) in the neonatal intensive care unit and to improve the ability of early diagnosis of the disease.Methods A total of 5 590 newborns were hospitalized in the Neonatal Intensive Care Unit (NICU),Fujian Maternity and Children Hospital between January 2012 and April 2015,and 340 neonates who were suspected of IMD consecutively were recruited.Tandem mass spectrometry and gas chromatography-tandem mass spectrometry were used to diagnose IMD.A retrospective study of analyzing the clinical characteristics of the patients of IMD in the NICU was conducted.Results Fifteen neonates were diagnosed as IMD,among whom methylmalonic academia,maple syrup urine disease,hyperphenylalaninemia,citrin deficiency,propionic acidemia,glutaric academia,ornithine transcarbamylase deficiency and primary carnitine deficiency were 5,2,2,2,1,1,1 and 1,respectively.Sixty-six point seven percent (10/15 cases) of IMD onset in the first week after birth were severe.Clinical presentations include the nervous was severe,digestive system and respiratory system symptoms,such as poor response,coma,lethargy,dystonia,convulsion,shortness of breath,dyspnea,milk refusal,diarrhea,jaundice,and so on.The main early manifestations were anorexia,lethargy,seizures and shortness of breath,which were nonspecific.Conclusions Clinical manifestations of IMD are nonspecific.The earlier onset of the disease is more serious,and early tandem mass spectrometry and gas phase chromatography-mass spectrometry are useful for early diagnosis and may guide early clinical intervention.
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Objective To identify the risk factors for nosocomial sepsis in preterm infants.Methods A case-control study (1 ∶ 2) was conducted in 81 preterm infants with nosocomial sepsis and 162 preterm infants without nosocomial sepsis as age-matched controls (admission time was the most closely) hospitalized in Fujian Maternity and Children Hospital from January 1,2007 to December 31,2011.Data of preterm infants including maternal,delivery and neonatal records were collected.Risk factors for nosocomial sepsis were analyzed using t test,x2 test and multivariate Logistic regression.Results Nosocomial sepsis occurred in 81 preterm infants with an incidence rate of 1.50％ (81/5 392).Univariate analysis showed that the gestational age [(31.8 ±2.4)vs(33.8 ± 1.8)weeks,t=-7.260,P＜0.01] and birth weight [(1 545± 349) vs (2 174±465) g,t=-10.750,P＜0.01] of neonates with nosocomial sepsis were lower than those in the controls.Compared with the controls,the neonates with nosocomial sepsis had higher incidence of small for gestational age [27.2％ (22/81) vs 11.7％ (19/162)],multiple birth [35.8％ (29/81) vs 21.6％ (35/162)],neonatal asphyxia [19.8％(16/81)vs 8.6％(14/162)],admission to neonatal intensive care unit [81.5％(66/81) vs 49.4％ (80/162)],incubator usage [87.7％ (71/81) vs 29.0％ (47/162)],intracranial hemorrhage [27.2％ (22/81)vs 14.2％ (23/162)],noninvasive ventilation [35.8％ (29/81)vs 14.8％ (24/162)],feeding intolerance [64.2％ (52/81) vs 17.9％ (29/162)],using probiotics [65.4％ (53/81) vs 37.0％ (60/162)],duration of parenteral nutrition ＞7 days [77.8％ (63/81) vs 16.0％ (26/162)],combined administration of antibiotics [61.7％(50/81) vs 43.8％(71/162)],duration of antibiotics administration ＞7 days [65.4％(53/81) vs 9.3％ (15/162)],intravenous immunoglobulin [76.5％ (62/81) vs 46.9％ (76/162)] and central vena catheterization [16.0％ (13/81) vs 1.2％ (2/162)] (all P＜0.05).The Logistic regression analysis showed that low birth weight (OR=2.087,95％CI:1.074 4.057),duration of parenteral nutrition ＞7 days (OR=3.075,95％CI:1.158 8.164),feeding intolerance (OR-4.328,95％CI:1.776-10.544) and duration of antibiotic administration ＞7 days (OR=18.443,95％CI:5.084-66.913) were independent risk factors for nosocomial sepsis in preterm infants (all P＜0.05).Conclusions Preterm infants with low birth weight,long duration of parenteral nutrition,long-term antibiotic treatment and feeding intolerance have high risk for nosocomial sepsis.
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Objective To study the change of Yes-associated protein (YAP) expression in rectal cancer and to explore the significance of YAP in rectal cancer.Methods Reverse transcriptase polymerase chain reaction(PT-PCR) and Western bloting technology were used to detect mRNA and protein expression of YAP in 30 patients with rectal cancer and 10 cases of normal rectal mucosa tissue.Results The expressions of mRNA and protein of YAP in rectal cancer were significantly higher than those in normal rectal mucosa tissue (73.2 ± 1 1.1 vs.10.4 ± 4.1,65.7 ± 9.5 vs.9.2 ± 4.3,P ＜ 0.05).Conclusion YAP high expression is related to the occurrence of rectal cancer.
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Objective To compare the efficacy and safety of oral ibuprofen and indomethacin for the closure of patent ductus arteriosus (PDA) in preterm infants and investigate the factors affecting the effect of indomethacin.Methods Two hundred and four preterm infants with symptomatic PDA were enrolled in this retrospective study.They were divided into two groups accroding to the admission date.From Jan.1,2007 to Dec.30,2009,44 infants orally administered ibuprofen (one course:first dose was 10 mg/kg,followed by two doses of 5 mg/kg at 24 h intervals) were as ibuprofen group.From Dec.31,2009 to Jan.31,2011,160 infants orally administered indomethacin (one course:0.2 mg/kg,at 12 h and 24 h intervals for three times) were as indomethacin group.Chisquare test,t test and rank sum test were used to compare the rate of ductal closure,side effects and complications of two groups.Influence factors of indomethacin therapy were analyzed with Logistic regression.Results There were no differences of overall ductal closure rate [77.3％ (34/44) vs 70.6％ (113/160),x2 =0.757,P＞0.05],one course therapy [68.2％ (30/44) vs 63.8％(102/160),x2=0.297,P＞0.05] and two courses therapy closure rate [9.1％ (4/44) vs 6.9％(11/160),x2 =0.030,P＞0.05] between i buprofen group and indomethacin group.The incidences of oliguria [＜1 ml/(kg ? h)] and high serum creatinine (＞88 μmol/L) of indomethacin group were higher than those in ibuprofen group [21.3％ (34/160) vs 6.8％ (3/44),x2=4.841,P=0.028;26.9％ (43/160) vs 9.1％ (4/44),x2=6.156,P=0.013].Logistic regression analysis showed that small gestational age (OR=2.563,95％CI:1.099-5.976,P=0.029),neonatal respiratory distress syndrome (OR=2.407,95％CI:1.023-5.664,P=0.044)and septicemia (OR=4.575,95％CI:1.782-26.768,P=0.009) were unfavorable factors for ductal closure in preterm infants underwent indomcthacin therapy,while antenatal steroid (OR=0.530,95％CI:0.312-0.901,P=0.018) was a favorable factor.Conclusions Oral ibuprofen have the same effects as indomethacin on PDA treatment in preterm infants,but with fewer side effects on renal function in terms of urine output and serum creatinine level.Some factors such as septicemia may affect the theraputic effects.
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Objective To determine the relationship between the levels of serum cortisol and patent conducted.Thirty-eight pairs of preterm infants were selected from January 1 to December 31 in 2009.Thirty-eight preterm infants developed PDA.And we also selected 38 non-PDA preterm infants as the controls,who had the corresponding gestational age,same exposure to antenatal steroid and sameechocardiography examination time.The serum cortisol concentrations of these infants were measured twice by chemiluminesence immunoassay.All data were analyzed via SPSS 13.0.Results No significant difference was found between PDA and control groups in demographic characteristics and influence factors for serum cortisol.The first mean level of serum cortisol in PDA group was (261.9± 229.6) nmol/L,significantly lower than that in control group [(379.8 ± 236.3) nmol/L] (t = 2.20,P = 0.03).Logisticregression analysis showed low serum cortisol concentrations at birth was risk factor for PDA in preterm infants(OR = 0.916,95% CI:0.854-0.983,P = 0.015).The second adjusted mean levels (95 % CI) of serum cortisol in PDA and control groups were 300.0 nmol/L(232.4-367.4 nmol/L) and 263.6 nmol/L (196.2-331.2 nmol/L),respectively.There was no significant difference between the two groups (t=0.537,P=0.466).Conclusions Low serum cortisol concentrations at birth is a risk factor for PDA in preterm infants,while the serum cortisol value may be not affected by PDA.
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Objective To investigate the effect of patent ductus arteriosus(PDA)on myocardial injury of premature infants.Methods From May 1,2010 to January 31,2011,110 preterm infants with gestational age from 28 to 36 weeks accepted echocardiography examination,and their blood samples were collected to determine cardiac troponin T(cTnT)and creatine kinase MB isoenzyme (CK-MB)levels 72 h and 3 d after deliveries.All subjects were divided into two groups according to the echocardiogram results:PDA group(n=44)and control group(n=66).The infants with PDA were treated with ibuprofen,and then echocardiography was taken again.cTnT and CK-MB were re-measured in both groups.Chi-square test,t-test,multi-variate linear regression and Spearman rank correlation test were perfomed for statistical analysis.Results Before treatment,cTnT[(0.259±0.134)μg/L]and CK-MB[(7.31± 2.69)μg/L]level of PDA group were significantly higher than those[(0.083±0.054)μg/L and(5.71±1.88)μg/L]of control group(t=9.557 and 2.588,P＜0.01 and ＜0.05,respectively).For 34 infants with successful treatment,cTnT and CK-MB levels decreased markedly to(0.062 ± 0.039)μg/L and(5.34 ± 1.50)μg/L,respectively(t =9.268 and 5.974,all P＜0.05),compared with those levels before treatment.For the ten infants failed to close ductus,the cTnT and CK-MB levels[(0.193±0.049)μg/L and(6.93±1.63)μg/L,respectively],were lower than those before treatment(t=1.525 and 0.766,all P＞0.05),while higher than those of the control group(t=9.068 and 4.055,P＜0.05).Level of cTnT positively related to the duration of ventilation,PDA and respiratory distress syndrome,while did not relate to gender,gestational age and birth weight.CK-MB level was associated to gender,gestational age,birth weight,duration of ventilatory support and PDA.In PDA group,the cTnT level was positively related to the diameter of the ductus,but not related to any indicators in echocardiography.Conclusions Symptomatic PDA could cause myocardial injury in preterm infants.The changes of blood cTnT and CK-MB were consistent with the severity of PDA.Serial measurements of blood cTnT and CK-MB might help to make early diagnosis and treatment for premature infants with PDA and myocardial injury.