ObjectiveTo recognize risk factors, types and prognosis of cerebral white matter injury i n preterm infants. MethodsThrough image examination, we obse rved the development of periventricular white matter injury in 64 preterm infant s. Follow-up was done to evaluate the mental development of them. We also anal yzed the perinaltal risk factors (maternal complications during pregnancy, and n eonatal diseases at early age) that related to periventricular leukomalacia (PVL ). Results Sixty-four preterm infants showed different d egrees of periventricular white matter injury: (1) Eighteen infants had PVL, of whom 6 had multi-site PVL, and 12 presented local PVL; (2) Eight infants had pe rsistent periventricular hyperecho; (3) Thirty-eight infants had transient abno rmality. Forty-six infants were followed up. The incidence of DQ≤75 was 100% a nd 33 33% in 6 infants with multi-site PVL and in 6 infants with local PVL res pectively. Logistic analysis showed that intraventricular hemorrhage (IVH) combi ned with expanded ventricle coorrelated with cerebral white matter injury. Babie s of mother who had pregnant complications had high incidence of PVL. ConclusionPeriventricular white matter injury, especially PVL is har mful in the prognosis of preterm infant. IVH combined with ventricular expansion is an important high risk factor of periventricular white matter injury.

Objective To study the changes of neuron-specific-enolase (NSE), S100B protein and neuropeptide Y (NPY) levels in serum and cerebrospinal fluid of children with viral encephalitis and their clinical significance. Methods The NSE, S100B protein and NPY levels in the serum and cerebrospinal fluid of 50 children with viral encephalitiswere were measured, and another 20 children without central nervous system infection were selected as controls. Results The NSE, S100B protein and NPY levels in the serum and cerebrospinal fluid of children with viral encephalitis[serum: (18.90 ± 5. 50)μg/L, (0. 57 ±0. 26) μg/L, (267. 3 ± 54. 7 ) μg/L; GSF: ( 10. 45 ± 4. 40) μg/L, (0. 93 ± 0. 53 ) μg/L, (347.2 ± 60. 6) μg/L] were higher than those in control group [serum: ( 10. 35 ± 2. 49 ) μg/L, ( 10 ± 0. 06 ) μg/L, ( 67. 8 ±22.5)μg/L;GSF:(3.96 ± 1.57)μg/L,(0. 29 ±0. 18)μg/L,(102.6 ±38.9) μg/L] ( P <0.01). The levels of serum and CSF NSE S100B protein and NPY in critical patient[serum: (21.93 ±5.39)μg/L,(0.71 ±0. 31)μg/L, (32. 5 ± 62. 8) μg/L;GSF: (13.05 ±4.41)μg/L, (1.23 ± 0. 66) μg/L, (407.3 ±68. 1 ) μg/L] were higher than ordinary patients [serum: ( 15.93 ± 4. 02 ) μg/L, ( 0. 42 ± 0. 14 ) μg/L,(234.7 ±51.2)μ.g/L;GSF:(8.05 ± 1.77) μg/L,(0. 63 ±0.26)μg/L, (320.2 ±59.5) μg/L] ( P <0. 01 ). Conclusion NSE, S100B protein and NPY can be used to evaluate encephalitis condition, brain damage degree and prognosis of viral encephalitis.

Objective To investigate the effect of neonatal hypoxic myocardial injury and bradycardia on cerebral hemodynamics and brain tissue regional oxygen saturation (rSO2),and to provide patho-physiological evidence for treatment of neonatal hypoxic-ischemic encephalopathy (HIE) in acute phase.Methods Ninety nine full-term newborns admitted into Department of Neonatology,Peking University First Hospital from December,2005 to December,2008 were enrolled in this study.There were 18 newborns with both myocardial injury and HIE (group 1),31 newborns with HIE but without myocardial injury (group 2) and 50 cases of neonatal jaundice (control group).From 3 to 7 days after birth,Doppler ultrasound was used to measure systolic velocity (Vs),diastolic velocity (Vd) and resistance index (RI) of the anterior cerebral artery; and brain tissue rSO2 was detected by near infrared spectroscopy.The differences among groups were compared by variance analysis and LSD test.Brain tissue rSO2 before and after treatment of 20 newborns with bradycardia for various causes were detected and the difference was compared by paired t test.Results (1) Vs of group 1,group 2 and the control group was (19.35±5.13),(29.35±4.28) and (32.62±7.47) cm/s respectively; Vd was (6.43±2.98),(11.21±3.16) and (11.50±3.03) cm/s; RI was 0.68±0.10,0.62±0.03 and 0.64±0.06; brain tissue rSO2 was (52.4± 2.8)％,(54.6±3.1)％ and (62.1±1.9)％.There were significant differences among the three group(F=29.999,19.393,5.283 and 137.952,P＜0.01).Vs,Vd and rSO2 of group 1 were lower than that of group 2 and the control group (P＜0.05).RI of group 1 was higher than that of group 2 and the control group (P＜0.05).Vs and rSO2 of group 2 were lower than that of control group,but there were no differences between the two groups in Vd and RI.(2) The brain tissue rSO2 of newborns with bradycardia after treatment was higher than that before treatment [(58.7±4.6)％ vs (50.9±3.2)％,t=6.239,P＜0.01].Conclusions The disturbance of cerebral hemodynamics and cerebral oxygenation in HIE newborns are aggravated by hypoxic myocardial injury.Stable heart rate might be very important to early treatment for HIE.

Objective To investigate the correlation between hypoglycemia and brain injury of newborns.Methods Medical records and follow-up data of 110 newborns with hypoglycemia (blood glucose level≤2.2 mmol/L) who admitted into neonatal department of Peking University First Hospital from December 2006 to December 2009 were studied.All patients were divided into 3 groups:no brain injury group,mild and severe brain injury group according to their clinical manifestation,cerebral radiological characteristics and cerebral functional tests.By using receiver operating characteristic (ROC) curve and x2 test,the potential optimal blood glucose level and duration of hypoglycemia for predicting brain injury were confirmed.Multivariate Logistic regression was taken to determine independent predictors for brain injury.The analyzed factors included gender,preterm/small for gestational age,hyperbillirubinemia,fetal distress,asphyxia,infection,seizures and maternal hypertensive disorder complicating pregnancy and hyperglycemia.Results Among the 110 hypoglycemia newborns,33 (30.0％) infants suffered from brain injury,of which 23 were mild and 10 were severe.Blood glucose ≤1.7 mmol/L had high specificity (73％) and sensitivity (60％)for predicting brain injury.When blood glucose≤ 1.7 mmol/L,the incidence of brain injury and severe brain injury was 43.6％ (24/55) and 18.2％ (10/55),which was higher than those [16.4％(9/55) and 0.0％ (0/55)] of patients whose glucose level ＞1.7 mmol/L(x2 =9.74 and 11.00,P＜0.01 respectively).Blood glucose ≤ 1.2 mmol/L had high specificity (100％) and sensitivity (81％) for predicting severe brain injury.When blood glucose ≤1.2 mmol/L,the incidence of severe brain injury was higher than that of the patients whose glucose level was higher than 1.2 mmol/L [34.5％ (10/29) vs 0.0％ (0/81),x2 =30.72,P＜0.01].Duration of hypoglycemia ≥12 h had specificity (100％) and sensitivity (36 ％) for predicting brain injury.When duration of hypoglycemia ＜12 h,the incidence of brain injury was lower than that of the patients whose duration of hypoglycemia≥12 h [21.4％ (21/98) vs 6/6,x2 =27.69,P＜0.01].Multivariate Logistic regression showed that fetal distress (OR=4.69,95％CI:1.47-14.97,P=0.009),glucose level≤1.2 mmol/L (OR =5.16,95％CI:1.56-17.03,P=0.007),duration of hypoglycemia≥12 h (OR=8 885 220 297.12,95％CI:0.00-∞,P =0.000) and maternal hyperglycemia (OR =3.34,95％CI:1.01-11.02,P=0.048) were independent risk factors for neonatal brain injury.Conclusions Low blood glucose level and prolonged hypoglycemia might induce injury of neurol system.Fetal distress and maternal hyperglycemia might increase the incidence of brain injury in newborns with hypoglycemia.

Objective To determine the prognosis and risk factors of neonatal cerebral infarction.Methods From January 2002 to December 2010,44 newborn infants were diagnosed with cerebral infarction by imaging examinations at Peking University First Hospital.The neurodevelopmental outcomes of these newborn infants were followed up and evaluated by clinical manifestations,Gesell development scale,cranial imaging,electroencephalogram and auditory evoked potential.Factors related to prognosis were analyzed with single and multi-factor Logistic regression analysis.Results Thirty-eight (86％) cases were followed up,and of these cases,five children died and the results of three were inconclusive due to small age (less than 6 months old).Among the remaining 30 children,neurodevelopmental outcome was normal in 15 cases and abnormal in the remaining 15 cases,thus,the incidence of sequelae was 50％ (15/30) and the mortality rate was 13％ (5/38).Of the 15 abnormal cases,all had cerebral palsy and movement retardation,eight cases had cognitive impairment,eight cases had epilepsy and five had visual impairment.The incidence of large cerebral infarction (more than one lobe) was 14/15,worse cranial imaging outcome (one month after treatment,cerebral infarction lesion still present or had expanded)was 13/15,and severe complications was 8/15 in the newborns with sequelae,which were higher than in those without sequelae (4/15,5/15 and 1/15,respectively) (x2=13.889,8.889 and 7.778,all P＜0.05).Logistic regression analysis showed that large cerebral infarction was a risk factor for sequelae (OR=38.500,95％C1:3.749-395.407,P=0.002),however,worse cranial imaging outcome (OR=8.563,95％CI:0.909-80.683,P=0.061) and severe complications (OR=18.024,95％CI:0.516-630.163,P=0.111) were not risk factors for sequelae.Cerebral infarction with middle cerebral artery injury had a high risk of movement retardation (OR=6.000,95％CI:1.172-3.725,P=0.025),and those with a large cerebral infarction were more likely to have epilepsy (x2=7.273,P=0.010).The incidence of large cerebral infarction in the newborn infants with cognitive impairment was 8/8,which was much higher than in those without cognitive impairment (46％,10/22),thus,infarct area may be related to cognitive ability (x2=7.273,P=0.010).Conclusions Neonatal cerebral infarction might result in many types of sequelae,with motor impairment being the most common form.A large cerebral infarction is more likely to result in abnormal neurodevelopmental outcome.

Objective To investigate the etiology,clinical characteristics and prognostic indicators of neonatal refractory seizures.Methods Forty-six newborns admitted to the neonatology ward of Peking University First Hospital from January 1,2000 till July 31,2011 with refractory seizures were chosen as the subject,and another 42 newborns with nonrefractory seizures who were admitted at the same period were chosen as the nonrefractory seizures group.The etiologies,clinical characteristics and prognosis of newborns in the two groups were compared.The newborns with refractory seizures were further divided into two subgroups:one was composed of 11 newborns with normal prognosis,and the other was composed of 35 newborns with unfavorable prognosis.The etiologies and clinical characteristics of seizure in thses two subgroups were also compared.Chi-square or Fisher's exact test was applied to compare the difference between groups; Logistic regression analysis was applied to determine the risk factors of refractory seizures and its prognosis.Results (1) The first three common causes of neonatal refractory seizures were severe perinatal brain damage (8/46,17.4％),encephalodysplasia (7/46,15.2％) and congenital metabolic diseases (3/46,6.5％).Seizure attack every day,severe abnormal electroencephalogram,statural convulsivus and unfavorable prognosis were significantly higher in the refractory seizure group than that in the nonrefractory seizures group [91.3％ (42/46) vs 57.1％ (24/42) ; 55.6％ (25/45) vs 5.4％ (2/37) ;17.4％(8/46) vs 0.0％(0/42) ; 76.1％(35/46) vs 21.4％(9/42),x2 =13.665,23.123,Fisher's exact test and 26.236,respectively,all P＜0.01].Seizure attack everyday (OR=3.811,95％CI:1.019-14.258,P =0.047) and severe abnormal electroencephalogram (OR =16.384,95％ CI:3.421-78.472,P=0.000) were independent risk factors of refractory seizures.(2) Among those newborns with refractory seizures and unfavorable prognosis,the failure rate of phenobarbital administration was 80.0％(28/35),higher than those with normal prognosis (4/11) (Fisher's exact test,P=0.010).Therefore,poor phenobarbital therapeutic efficacy indicated an unfavorable prognosis (OR=12.444,95％CI:2.530-61.217,P=0.002).Conclusions The common causes of neonatal refractory seizures are perinatal brain damage,encephalodysplasia and congenital metabolic diseases.The clinical characteristics of refractory seizure are frequent seizure attacks (more than once a day),severe abnormal electroencephalogram and statural convulsivus,and unfavorable prognosis is common.Poor therapeutic effect of phenobarbital prompts adverse outcome.

Two kinds of different functional groups modified RuBpy-doped silica fluorescent nanoprobes Probe A and B that conjugated with avidin were prepared for the recognition of liver cancer cells. Firstly RuBpy-doped silica nanoparticles were synthesized by reverse microemulsion and modified with different functional groups, then Probe A was prepared by the conjugation of avidin with carboxyl modified nanoparticles through covalent binding using 1-ethyl-3-( 3-dimethylamino propyl ) carbodiimide hydrochloride ( EDC )/sulfo-NHS, whereas Probe B was prepared by the conjugation of avidin with the polyethylene glycol ( PEG) linkers on the surface nanoparticles using cyanogen bromide method. Therefore, compared with Probe A, Probe B was obtained by coupling avidin to the nanoparticles through long-chain PEG molecules. The two probes were incubated with liver cancer cells respectively, and microscopic fluorescence imaging shows that Probe B which contained PEG molecules could be more effectively applied for the recognition of tumor marker carcinoembryonic antigen ( CEA) in liver cancer cells.

Objective To analyze and summarize clinical manifestations of inflammatory bowel disease (IBD) in neonates.Methods From 2007 to 2013,three neonates were diagnosed with IBD in Peking University First Hospital.Data on these three cases with neonatal IBD were analyzed.The coding region of the interleukin 10 receptor A (IL10RA) gene was detected using direct Sanger sequencing in one of the patients.The literature was reviewed.Results The three newborns were 4-12 days old,all had symptoms of diarrhca,mucosanguineous feces and oral ulcers,accompanied by hypoalbuminemia and a family history.Two of these infants had perianal lesions,and one had liver damage and scizures.All three patients had elevated white blood cells and were anti-proteinase 3 positive.Two had elevated C-reactive protein and erythrocyte sedimentation rate,and one had positive antinuclcar antibodies and double stranded DNA antibodies.Colonoscopy showed multiple ulcers affecting the ileocecum and colon.The infants received treatment including antibiotics,switching formula feeding and 5-aminosalicylic acid.After treatment,one infant was cured,one died although glucocorticoids and azathioprine were used,and the other with a IL10RA gene mutation recovered,this infant had a compound heterozygous mutation with c.301C ＞ T (p.Arg101Trp),c.421G ＞ A (p.Gly141Arg) and whose parents were carriers.The literature review showed that fever and abnorrnal defecation were the main clinical features,and examination of serum antibodies showed a lower positive rate.The patients had a poor response to medications and most required surgery.IL10RA gene mutations were detected in some patients.Conclusions Neonates with diarrhea and a family history may have IBD and should undergo colonoscopy as early as possible.

Objective To study the clinical features,diagnosis and treatment of neonatal very early onset inflammatory bowel disease(VEO-IBD) to improve the diagnosis and treatment of the disease.Method From Jan 2013 to Dec 2015,five infants with VEO-IBD admitted to Peking University First Hospital were reviewed and analyzed.Their clinical data included general condition,clinical symptoms,laboratory tests,autoimmune antibodies (ANCA,dsDNA,ANA and ENA),colonoscopy,pathological results and therapeutic response.Interleukin-10 receptor A (IL-10RA) gene was examined in all patients.All the patients were followed up for more than 1 year.Result Three of the five patients had a family history.Persistent diarrhea was the most common presenting symptom.One of them received surgery because of intestinal necrosis and developed typical symptoms of IBD half a year later.Bloody stool or positive fecal occult blood test were found in all infants.Fever,anemia,oral ulcer,perianal lesions and malnutrition were common concomitant symptoms.Most of the patients had elevated WBC,CRP and ESR,and 4 of them had positive autoimmune antibodies.Colonoscopy showed multiple ulcers affecting the colon.Intestinal biopsies revealed acute and chronic inflammation.4 of patients were found to have cryptitis and crypt abscesses.Gene sequencing revealed IL-10RAgene mutation in all five patients,including 1 case with homozygous mutation and 4 heterozygous mutations.4 patients received steroid and mesalazine therapy and only 1 patient's symptoms were controlled.However,the colonoscopy result was still abnormal in this patient.4 patients had poor response to further infliximab and (or) thalidomide therapy.1 of them received surgery because of intestinal obstruction at 2-year-old.Conclusion Neonatal VEO-IBD was associated with IL-10RA gene mutation.The patients had severe symptoms and poor response to conventional medications.The effects of biological agents and thalidomide were still not sure.

ObjectiveTo analyze the characteristics of neonatal hyperammonemia and citrullinemia caused by argininosuccinate lyase (ASL) gene mutations, and to have a better understanding of this disease. MethodsA neonatal patient with the onset of hyperammonemia and citrullinemia admitted to the Department of Pediatrics of Peking University First Hospital on April 2, 2014, was retrospectively studied. Peripheral blood leukocyte DNA of the patient and his parents was collected to detectASS1,ASL andSLC25A13 gene mutations. The literature related to neonatal hyperammonemia, citrullinemia and argininosuccinic aciduria was reviewed. ResultsThe baby in this case appeared lethargic, had weaker crying and food refusal since three days after birth, and analysis of blood amino acid found a marked increase in blood ammonia (1 332μmol/L) and a significant rise in citrulline (759.12μmol/L). Sanger sequencing detection revealed compound heterozygous mutations in theASL gene (c.434 A>G, c.857A>C) and this c.857A>C mutation was the first reported case in China. This case of hyperammonemia and citrullinemia was confirmed as argininosuccinic aciduria caused by ASL gene mutations. A protein-limited diet and the treatment of arginine and L-carnitine were given. His blood ammonia decreased to normal level and there was a significant improvement in physical and intellectual progress at five months old. Unfortunately, he had an intestinal infection when he was over five months old and the blood ammonia level tested in the local hospital was 480μmol/L. Gradually there was a disturbance of consciousness, then coma, and he finally died after active rescue in the local hospital.ConclusionsHyperammonemia and citrullinemia in neonates are likely to be argininosuccinic aciduria and a gene mutation test may be helpful for diagnosis.