Objective To study the effects of discoidin domain receptor 1 (DDR1) mediated phosphorylation of protein Tau on hypoxic-ischemic brain damage (HIBD) in neonatal rats and its possible mechanism.Methods Sixty-four seven-day-old male specific-pathogen-free Wistar rats were randomly divided into four groups with sixteen in each: Sham, HIBD, HIBD with normal saline (HIBD+NS) and HIBD with DDR1 inhibitor (HIBD+DI) groups. A rat model of HIBD was established by subjecting the rats to left common carotid artery ligation, followed by exposing them to hypoxia for two hours. In HIBD+DI group, the inhibitor of DDR1 was immediately injected into lateral cerebroventricles of the rats following modeling. Forty-eight hours after injection, tissues of left cerebral cortex were collected from each rat to evaluate histopathological changes with HE staining. Western-blotting was used to assess the phosphorylation levels of DDR1 and protein Tau. Enzyme-linked immunosorbent assay was performed to detect the concentrations of acetylcholine. Analysis of variance ort test were used for statistical analysis.Results (1) Damages in cerebral cortex: Percentages of abnormal neurons in the rats of HIBD group were higher than those in Sham group [(80.28±4.51)% vs (10.40±2.17)%,t=39.491,P<0.01]. Pyknotic or necrotic neurons in the rats of HIBD+DI group were less than those in HIBD+NS group [(31.91±3.05)% vs (82.01±7.20)%,t=18.123,P<0.01]. (2) Phosphorylation of DDR1 and protein Tau: Levels of phosphorylated DDR1 in the cerebral cortexes of rats in HIBD group were higher than those in Sham group (0.922±0.199 vs 0.095±0.023,t=10.379,P<0.01), and those levels in HIBD+NS group were higher than those in HIBD+DI group (1.200±0.171 vs 0.255±0.111,t=11.901, P<0.01). The phosphorylation of protein Tau was similar to that of DDR1 (0.919±0.228 vs 0.194±0.224 in HIBD and Sham groups,t=7.347; 1.100±0.167 vs 0.291±0.210 in HIBD+NS and HIBD+DI groups,t=9.447;bothP<0.01). (3) Levels of acetylcholine: Levels of acetylcholine in cerebral cortexes of rats in HIBD group were lower than those in Sham group [(3.685±0.472) vs (7.429±0.861) ng/g protein,t=10.781,P<0.01], and that levels in HIBD+DI group were higher than those in HIBD+NS group [(7.058±0.915) vs (2.521±0.723) ng/g protein,t=10.989,P<0.01].Conclusions Activation of DDR1 plays a key role in enhancing the phosphorylation of protein Tau and in reducing the secretion of acetylcholine in cerebral cortexes of rats with HIBD. Inhibitor of DDR1 could protect neonatal rats from HIBD through the decreasing of protein Tau phosphorylation and increasing of acetylcholine release by inhibiting the activation of DDR1.

Objective To investigate the incidence and clinical presentation of breast milk transmitted cytomegalovirus (CMV) infection among preterm infants with birth weight≤1500 g.Methods Preterm infants enrolled in this study met the following inclusion criteria: birth weight≤1500 g, fed with CMV-positive breast milk and admitted into Neonatal Intensive Care Unit of Children's Hospital of Fudan University within 72 hours after birth from October 2015 to July 2016. And those with congenital digestive tract malformation or congenital CMV infection were excluded. Breast milk and infants' urine samples were regularly screened for CMV DNA by fluorescent quantitative polymerase chain reaction. Symptoms and laboratory findings in infants with CMV infection transmitted via breast milk were documented and analyzed. Differences in relevant parameters were analyzed usingChi-square test, Fisher's exact test,t test or Mann-WhitneyU test where appropriately.Results Sixty preterm infants breastfed with CMV DAN-positive milk were recruited. Among them, 19 (31.7%) developed breast milk-acquired CMV infection as their urine samples were positive for CMV DNA, while the others were negative for CMV DNA (infected group:n=19; non-infected group:n=41). The average CMV copies in breast milk, gestational age and birth weight of the infected group were all significantly higher than those of the non-infected group [3.76 (3.18-4.50) vs 3.47 (3.00-4.88) Log10 copies/ml,Z=-2.042;(30.4±2.1) vs (28.4±2.3) weeks,t=3.175; 1290 (750-1500) vs 1110 (575-1480) g,Z=-2.837; all P<0.05). Fewer infants in the infected group than in the non-infected group received blood transfusion [5/19 vs 56.1%(23/41),χ2=4.627,P<0.05]. Ages of the infants with CMV infection ranged from 26 to 164 days (median age of 92 days). Six out of the 19 infants had clinical symptoms concurrent with viral excretion in urine and the ages of these symptomatic infants of infection were earlier than those of the asymptomatic ones without significance [(72±34) vs (97±28) days,t=-1.710,P>0.05]. Four infants (21.1%, 4/19) had severe organ damage and/or positive IgM antibodies to CMV in serum, and were treated with antiviral therapy. Two had mild symptoms and were not given antiviral therapy. All of the six symptomatic infants were followed-up for one to six months, during which time the complete blood cell count and results of biochemical test and fundus examination were back to normal.Conclusions The incidence of breast milk-acquired CMV infection among preterm infants with birth weight≤ 1500 g was 31.7%, and no severe symptoms were reported in this study.

Objective To investigate the rate of termination of pregnancy (TOP) in gravidas with prenatally diagnosed fetal malformation and to analyze the influences of medical and non-medical factors on decision making.Methods This was a prospective cohort study. Gravidas who took part in a multidisciplinary consultation due to fetal malformation and finished a questionnaire after consulting from September 12, 2012 to May 2, 2013 were recruited. Exclusion criteria were chromosomal disorders and isolated abnormal ultrasound soft markers. The questionnaire survey was conducted to understand the patient's backgrounds and to collect their feedbacks on the consultation. Decisions of the gravidas on TOP were followed up by phone in 2014 and 2016. If a gravida chose to continue her pregnancy, her baby's outcome was also recorded.T test,Chi-square test or Fisher's exact test, or rank-sum tests (Mann-Whitney or Wilcoxon) or Logistic regression was used for statistical analysis.Results (1) Altogether 229 gravidas were recruited and 10 of them were lost to follow-up, so 219 cases were finally analyzed. Among the 219 cases, 35.6% (78/219) chose to terminate their pregnancies. (2) Neonatal prognosis was predicted based on the type and severity of the disease and was divided into four levels including good prognosis (122 cases, 55.7%), medium prognosis (20 cases, 9.1%), poor prognosis (17 cases, 7.8%) and unsure prognosis (60 cases, 27.4%). (3) Gravidas who chose to terminate their pregnancies were younger than their counterparts choosing to continue to term (average age: 27.8±4.1 vs 29.0±3.9,t=2.257,P<0.05). Gravidas who went to the consultation before the 24th gestational week carried double risk of TOP than those after the 24th gestational week [termination rate: 52.5% (31/59) vs 29.4% (47/160),χ2=10.089,P<0.01). (4) Gravidas with fetal growth restriction (FGR) were at triple risk of TOP than those without (OR=2.850, 95%CI: 1.323-6.140) after adjusting for maternal age, gestational age at consultation and prognostic evaluation. Comparing with the good prognosis group, in which the rate of TOP was 19%, the unsure (OR=2.354, 95%CI: 1.108-5.004), medium (OR=16.188, 95%CI: 4.732-55.372) and poor (OR=14.515, 95%CI: 3.61-58.359) prognosis groups had higher risk of TOP. (5) There were 63 women informed us their reasons for TOP (multiple choices), among which 57 (90.5%) were due to unsure neonatal outcomes, and 10 (15.9%) were due to emotional factors. (6) Maternal satisfaction with neonatal prognosis was 2 to 5 points (medium score, ten-point system) lower in gravidas choosing to TOP than in those choosing to continue pregnancy regardless of good, unsure, or medium neonatal prognosis. No significant difference in maternal satisfaction was found among gravidas with poor neonatal prognosis.Conclusions The rate of TOP in gravidas with prenatally diagnosed fetal malformation remains high in China. Factors that can negatively influence the rate of TOP are consultation after the 24th gestational week, better perceived neonatal prognosis and higher maternal satisfaction with neonatal prognosis. Uncertainty of the neonatal prognosis is the leading cause of maternal dissatisfaction.

Objective To investigate the prenatal diagnosis and postnatal clinical outcomes of fetal congenital choledochal cyst (CCC) to improve the recognition and treatment of fetal CCC.Methods Clinical data of 23 cases of fetal CCC which were diagnosed during routine prenatal ultrasonic examination in Jinhua Municipal Central Hospital from June 2009 to May 2015 were retrospectively analyzzed. Maternal age, gestational age at diagnosis of CCC, location and size of cyst, postnatal examination, age at operation and follow-up outcomes were recorded and statistically analyzed by Wilcoxon rank-sum test.Results (1) Among the 23 cases, six (26%) were terminated and the rest 17 continued their pregnancies (74%). (2) Results of the prenatal ultrasonography of the 23 cases indicated that hepatic portal cysts were closely related to hepatic portal veins or arteries. Six of the cysts communicated with gall bladder and eight connected to intrahepatic bile duct. The maximum diameter of the cysts in the 23 cases was 16.0-31.0 mm, averagely (24.7±3.7) mm. The maximum diameter of cysts diagnosed in the third trimester was significantly larger than that in the second trimester [ 27.0 (22.0-31.0) vs 23.0 (21.0-25.0) mm,Z=-2.134,P<0.05]. (3) Among the 17 cases of continued pregnancy, one underwent cesarean section at 35+ weeks of gestation and 16 delivered at term with the average gestational age at delivery of (38.2±1.1) weeks. All neonates were re-examined by abdominal ultrasound at 1-2 postnatal weeks and confimed prenatal diagnosed of CCC. (4) The 17 neonates were re-examined by abdominal ultrasound during the second postnatal week and the results showed that cyst size remained the same in four, decreased in one and gradually increased with the gestational age in 12 neonates. Among the 16 cases of confirmed CCC, 12 received surgery, including 11 (Ⅰa, 6;Ⅰc, 3;Ⅳb, 2) within one year-old and one (Ⅰc) around 18 months old. The prognosis was uneventful. Four out of the 16 cases rejected surgical operation and were followed up in outpatient. One neonate was diagnosed with congenital biliary atresia and transferred to Children's Hospital for operation.Conclusions When fetal abdominal cyst presented with hepatic portal cyst which communicates with gallbladder or intra-hepatic duct in ultrasonography, a congenital choledochal cyst should be taken into consideration by excluding the possibility of biliary atresia in the first place. Surgery for CCC infants without symptoms or signs is suggested to be performed around three months after birth. The postoperative prognosis of CCC is favorable, so termination is not recommended for gravidas with fetal CCC in prenatal consultation.

Objective To investigate the association between high-frequency oscillatory ventilation (HFOV) and the incidence of brain injury in premature infants(BIPI) with respiratory distress syndrome (RDS).Methods A total of 136 premature infants who were diagnosed as RDS and treated with mechanical ventilation between January 1,2014 and June 30,2016 were enrolled.Atter stratified by gestational age of 36-34 weeks,33-32 weeks,31-28 weeks and ≤ 27 weeks,the neonates were randomly divided into two groups (68 cases each):conventional mechanical ventilation (CMV) and HFOV groups.Duration of ventilation and changes in blood gas parameters following 24,48 and 72 hours of ventilation were monitored and compared between the two groups.Incidences of BIPI and complications in the two groups were calculated and their associations with gestational age and birth weight were analyzed.Moreover,incidences of cure rates in the two groups were comparatively analyzed.Independent samples t-test,two-way analysis of variance,Chi-square test or Fisher's exact test was used for statistical analysis.Results (1)Significant difference was observed neither in the perinatal factors (prenatal glucocorticoid usage,and incidences of premature rupture of membrane and gestational diabetes mellitus),nor in the severity of RDS between the two groups (all P＞0.05).(2) The average duration of ventilation in the CMV group was higher than that of the HFOV group [(68.44±10.3) vs (64.7±8.5) h,t=2.285,P＜0.05].No significant difference in the values of pH,partial pressure of carbon dioxide (PaCO2) or partial pressure of oxygen (PaO2) before and after 24,48 or 72 hours of ventilation treatment was found between the two groups (all P＞0.05).(3) Neither the incidence of hemorrhagic brain injury nor that of non-hemorrhagic brain injury showed any significant difference between the CMV and HFOV groups [36.8％ (25/68) vs 39.7％ (27/68);16.2％ (11/68)vs 14.7％ (10/68),both P＞0.05].The total incidence of BIPI showed no significant difference [44.1％(30/68) vs 45.8％(33/68),22=0.266,P=0.606].The smaller gestational age at birth and the lower birth weight,the higher incidence of BIPI,although no significant difference was shown in the incidence of BIPI when compared among different gestational age groups and different birth weight groups (all P＞0.05).(4) The incidence of complications in the CMV group was higher than that in HFOV group [25.0％(17/68) vs 11.8％(8/68),22=3.970,P=0.044],while the cure rate of RDS was similar [94.1％(64/68) vs 95.6％(65/68),x2=0.151,P=0.703].Conclusions HFOV is a safe and reliable therapy for preterm infants with RDS.Compared with CMV,HFOV can shorten the duration of ventilation and reduce the incidence of complications without increasing the risk of BIPI.However,the cure rate of RDS is not increased by HFOV.

Objective To investigate the levels of antibody to pertussis toxin (PT) IgG in newborns in Shunyi Women and Children's Hospital of Beijing Children's Hospital in 2016.Methods A total of 419 newborns were enrolled in this study.Umbilical cord blood sample was collected from each subject and detected by enzyme-linked immunosorbent assay to measure the concentration of PT-IgG.Besides,all newborns were followed up to January 31,2017.Chi-square test was used for statistical analysis.Results The detectable rate of umbilical cord blood samples for PT-IgG accounted for 30.1％ (126/419).The median antibody level was ＜ 5 U/ml,and the 90th and the 95th percentile were 14.3 and 24.0 U/ml,respectively.No cases of pertussis occurred at the end of follow-up.Conclusions The newborns born in Shunyi Women and Children's Hospital of Beijing Children's Hospital are generally lack of protective PT antibody.

Objective To identify the epidemiological changes in invasive fungal infection (IFI) in a neonatal intensive care unit (NICU) to provide information for prevention and treatment of IFI.Methods A total of 102 cases who were diagnosed with IFI among 42 187 neonates hospitalized in the NICU of Affiliated BaYi Children's Hospital,Chinese People's Liberation Army General Hospital from January 1,2009 to December 31,2014 were enrolled in this study.Since January 1,2012,the divisions of our NICU were more specific and intravenous fluconazole was administered as a routine preventive measure for high-risk infants.Clinical information of the IFI cases including general features,incidence,distribution of pathogens and drug (Amphotericin B,Fluconazole,Flucytosin,Itraconazole and Voriconazole) sensitivity were analyzed between former period (January 1,2009 to December 31,2011) and latter period (January 1,2012 to December 31,2014) by Chi-square test.Results The total incidence of IFI was 2.42‰ (102/42 187),and among the 102 IFI cases,73.5％ (75/102) were preterm infants and 75.5％ (77/102) were low birth weight infants.The incidence ofIFI in the latter period was lower than that in the former period [1.8‰ (48/26 046) vs 3.3‰ (54/16 141),x2=9.329,P＜0.01].The incidences of IFI in neonates with gestation age ＜28,≥ 28-＜32 and ≥ 32-＜37 weeks in latter period were decreased as compared with those in former period [10.6 ‰ (3/284) vs 76.9 ‰ (9/117),x2=12.569;6.1‰ (13/2 134) vs 21.9‰ (28/1 277),x2=16.868;1.4‰ (12/8 706) vs 1.9‰ (10/5 256),x2=7.165] (all P＜0.01).Altogether 103 pathogen strains were identified from 102 IFI cases as one Candida parapsilosis strain and one Laurent cryptococcus strain were both isolated from one patient.The most prevalent three pathogens were Candida albicans [51.5％ (53/103)],Candidaparapsilosis [24.3％ (25/103)] and Candida glabrata [8.7％ (9/103)].The isolated rates of Candida albicans and Candida glabrata strains in the latter period were higher than those in the former period [63.3％ (31/49) vs 40.7％ (22/54),x2=5.218;18.4％ (9/49) vs 0.0％ (0/54),x2=10.868],while the isolated rate of Candida parapsilosis strain was lower in the latter period than that in the former period [12.2％(6/49) vs 35.2％(19/54),x2=7.355] (all P＜0.05).All pathogen strains were sensitive strains except one Candida krusei strain which was isolated in the former period and was resistant to Fluconazole.Conclusions Premature infants born at lower gestational ages or with low birth weights are still at high-risk of IFI,but the incidence of IFI has declined in recent years.Routine administration of fluconazole in high-risk infants in NICU could prevente IFI without increasing drug resistance.Candida albicans is the predominant pathogen ofIFI.

Objective To explore the influence of delivery mode and feeding pattern on cytomegalovirus (CMV) infection on infants born ≥ 32 gestational weeks,and to observe the outcomes after CMV infection.Methods In this retrospective study,378 pregnant women with positive CMV IgG and negative CMV IgM,and their offsprings (384 cases,including six pairs of twins),who got visited at five hospitals of our collaboration group during March 2013 and February 2016,were enrolled.Serum samples were retrieved from a previous study of these participants for CMV IgM and IgG detection with enzyme-linked immunosorbent assay.All participants were divided into exclusive artificial feeding (EAF) and breastfeeding groups (BF),and the latter included exclusive breastfeeding (EBF) and mixed feeding (MF).T or Chi-square or Fisher's exact tests were performed for statistical analysis.Results (1) Among the 378 pregnant women,there were 186 mothers and 190 infants (4 pairs of twins) in BF group,and the other 192 mothers and 194 infants (2 pairs of twins) in EAF group.The percentage of male infants were 54.7％(104/186) and 56.2％(109/194) in the BF and EAF group,respectively.The mean birth age was (38.9± 1.4) and (38.7± 1.7) weeks,and the age at followingup was (9.8± 2.2) and (10.5± 2.9) months,respectively.(2) The CMV IgG positive rate of infants in BF group was higher than in the EAF group [62.6％(119/190) vs 29.9％ (58/194),x2=41.403,P＜0.001].CMV IgG levels in infants were higher than the mothers [(537.1 ±249.5) vs (416.2±241.2) U/ml,t=4.609,P＜0.001].In infants with positive CMV IgG,the positive rates of CMV IgM were similar in the two groups [21.0％(25/119) vs 19.0％ (11/58),x2=0.101,P=0.751].(3) The positive rate of CMV IgG in vaginally born infants was higher than those born by caesarean section [55.2 (95/172) vs 38.7％ (82/212),x2=10.472,P=0.001].Further analysis in the EAF group showed that those infants born vaginally had a higher positive rate ofCMV IgG than those born by caesarean section [42.9％ (33/77) vs 21.4％ (25/117),~=10.231,P=0.001],while this figure did not show statistical difference in the BF group.(4) Infants with positive or negative CMV IgG were in similar age and gender proportion,as well as their height and weight.Among 36 infants with both positive CMV IgG and IgM,three failed in alanine aminotransferase (ALT) test due to hemolysis.However,among the other 33 cases,15.1％ (five cases) presented with lightly elevated ALT (42-107.2 U/L),which was similar to those infants with positive CMV IgG and negative CMV IgM (14/98,14.3％) and those with both negative CMV IgG and IgM (20/144,13.9％),(x2=0.036,P=0.982).Conclusions Although breastfeeding and vaginal birth may increase CMV infection rate in neonates and infants,but no obviously adverse prognosis was reported in those born over 32 gestational weeks.So we should encourage vaginal birth and breastfeeding in these population.

Objective To analyze the incidence,risk factors,clinical characteristics and pregnant outcomes of perinatal pulmonary embolism(PPE).Methods Clinical data of eight patients who were admitted to Beijing Friendship Hospital of Capital Medical University for PPE from January 2006 to March 2016 were collected.General condition,symptoms,laboratory examinations,images,treatments and outcomes of these patients were analyzed retrospectively.Results The ten-year incidence of PPE was 0.029％ (8/27 560) in this hospital.Among the eight cases,two cases were diagnosed in the first trimester,and treated successfully by thrombolytic therapy.But one of two cases stopped growth,while the other one was premature labor.There were one case in the third trimester who had successful anticoagulant therapy and five cases in the postpartum period after cesarean delivery.Among the five cases,three cases were recovered after anticoagulant therapy,one case was recovered after thrombolytic therapy and one case died.All of the eight patients were immobilized before the onset of PPE,and five of them were diagnosed after cesarean section.Four out of the eight patients were obese.Five patients had three or more high-risk factors for pulmonary embolism and the other three had two.Conclusions It is necessary to pay close attention to gravidas who have two or more high-risk factors of PPE due to its fatal outcome.

Objective To study the epidemiological and clinical characteristics ofpertussis in infants younger than three months.Methods Infants younger than three months were enrolled from January 1,2011 to December 31,2015 with one or more of the following symptoms:persistent cough,spasmic cough,cyanosis of unknown causes,asphyxia and apnea.Multiplex polymerase chain reaction(PCR) assay was performed to identify Bordetella pertussis and enzyme-linked immunosorbent assay was used to detect antibody to pertussis toxin.Clinical features,complications,treatments and prognosis of the infants confirmed with pertussis were analyzed.Results Altogether 202 cases were enrolled in the five years,and 59 (29.2％) of which were positive for pertussis confirmed by multiplex PCR.Among the 59 cases,37 were boys and 22 were girls.The youngest baby was 13 days and the oldest one was 85 days.Length of stay ranged from 7 to 21 days.Twelve cases had a contact history with family members having chronic cough.Symptoms occurred in spring or summer in 46 cases (78.0％),and in autumn or winter in 13 (22.0％) cases.Symptoms of spasmic cough,cyanosis after coughing,vomiting after coughing and conjunctival hemorrhage were respectively found in 41 (69.5％),36 (61.0％),39 (66.1％)and 33 (55.9％) cases,while only six (10.2％) presented with inspiratory whooping sound on coughing.Fortynine cases (83.1％) showed increased lymphocyte count (≥ 10 × 109/L).Twenty-eight cases (47.5％) developed severe pertussis.Complications including apnea and bradycardia after coughing,respiratory failure and heart failure,pertussis encephalopathy as well as highly increased leucocyte count (≥ 60× 109/L) occurred in 23 (39.0％),18 (30.5％),five (8.5％) and four (6.8％) cases,respectively.Twenty-four cases with severe pertussis required respiratory support,of which six received invasive ventilation and 18 received non-invasive ventilation.Fifty-eight infants were recovered and discharged,while one baby died.Conclusions Bordetella pertussis infection is an important cause of persistent cough in unimmunized infants under three months of age.The symptoms of pertussis in infants are untypical,but the incidence of severe pertussis is high.Thus early diagnosis and timely treatment are necessary.