OBJECTIVE: To explore the circadian distribution of premature ventricular contractions (PVCs) in patients with viral myocarditis (VM) according to the theory of chronomedicine in traditional Chinese medicine (TCM) in order to find out the scientific evidence for a reasonable administration time. METHODS: Two hundred and forty patients with VM were enrolled and electrocardiograms were examined for all by Holter monitor. The circadian distribution of PVCs was evaluated according to the theory of chronomedicine of TCM about time periods corresponding to five zang viscera. RESULTS: PVCs mostly happened in periods of 3:00-5:00, 5:00-7:00, 7:00-9:00 and 9:00-11:00, in which 5:00-7:00 was the most serious time. Less PVCs happened in periods of 17:00-19:00, 19:00-21:00 and 21:00-23:00. The frequency of PVCs in midnight also increased with aging. The time periods of the frequency peak of PVCs in patients with different syndromes were also different. In patients with syndrome of pathogenic heat invading heart (PHIH), the PVCs mostly appeared in midday. In patients with syndrome of flaring of fire due to yin-deficiency (FFYD), the PVCs were most serious in daytime and aggravated at noon. And in patients with syndrome of insufficiency of heart-qi and yang (IHQY), the PVCs mostly happened in early morning or midnight. CONCLUSION: There was a manifest regulation of the pathological circadian rhythm of PVCs in patients with VM. The circadian distributions of PVCs were variable in patients with different syndromes. Therefore the theory of chronomedicine of TCM may be used to guide the treatment based on syndrome differentiation.

Objective To study the apoptosis of gallbladder carcinoma cell line GBC-SD induced by antisense oligodeoxynucleotide (ASODN) targeting survivin. Methods ASODN targeting survivin was transfected into GBC-SD cells mediated by lipofectin. Cultured cells were divided into 3 groups: control group,sense oligonucleotide (SODN) group and ASODN group. After transfected for 16 h, the cultured cells were harvested and the following texts were carried out. The expression of survivin mRNA was detected by RT-PCR. Flow cytometer were used to detect apoptosis. Morphological changes were observed by electron microscopy. Results The expression of survivin mRNA was decreased 47.83% in ASODN group while apoptosis was increased from (0.50?0.23)% to (26.28? 3.91)%. Abnormal morphological changes of cells were observed in ASODN group and apoptosis bodies were found in some gallbladder carcinoma cells. Conclusion The expression of survivin may be decreased in GBC-SD cells after ASODN transfection.ASODN targeting survivin could induce gallbladder carcinoma cells apoptosis effectively.

Objective To evaluate the usefulness of functional magnetic resonance imaging (fMRI) as a noninvasive method in recording the activities of the human brain as excited by low frequency current(LFC) stimulator. Methods The right common peroneal nerves of 6 healthy volunteers were stimulated with LFC (NMR-II stimulator). The activities of the brain were then recorded and evaluated during the scanning by the fMRI technique. Data obtained during the study were dealt with with the software SPM99. Results In both cerebral hemispheres, the area where the postcentral and superior temporal gyrus, inferior parietal lobule met were excited, and so were the operculum at both sides. Postcentral gyrus, superior parietal and paracentral lobule, and the precuneus in the left cerebral hemisphere, as well as the superior occipital gyrus and the superior parietal lobule in the right hemisphere,were involved as the excited areas. Conclusion fMRI is a useful tool for recording and evaluating the brain activities excited by LFC.

Objective: To investigate the effect of survivin and bcl-2 antisense oligodeoxynucleotides ( AsODN) combined transfection on the human gallbladder carcinoma cell line GBC-SD in vitro. Methods: Survivin and Bcl-2 protein expressions were detected by immunohistochemical method; Cultured cells were divided into 4 groups: Nomal control group, survivin antisense observed group, bcl-2 antisense observed group and combined group. After transfected for 24 h, the expression of survivin mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Cell morphological changes were observed under electron microscopy. Apoptosis index (AI) was examined by flow cytometry; Inhibitory rate (IR) was determined by the colorimetri MTT cell viability and proliferation assay. Results: Survivin and Bcl-2 protein were highly expressed in gall bladder carcinoma cells; The expression of survivin mRNA was decreased 47. 8%. Abnormal morphological changes of cells were observed in the three AsODN transfection groups; The AI in survivin antisense observed group,bcl-2 antisense observed group,and combined group was 11.38%?3.91% , 9.26%?4.15% , 28.45%?6.34% respectively and significantly higher than the nomal control group (P

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 neonatal infectious disease and brain injury.MethodsClinical data of 1266 newborns with infectious diseases were collected from Peking University First Hospital from November 2005 to August 2010.The occurrence of brain injury was summarized.Related factors of brain injury caused by infection and the risk factors for severe brain injury were analyzed by Logistic regression model. Results Among the newborns with neonatal infectious diseases, the incidence of brain injury was 8.6％(108/1266), including 101 (8.0％)mild cases and seven (0.6％) severe cases. The incidence of brain injury for the newborns with severe infectious diseases was higher than those with mild infectious diseases [38.7％(29/75) vs 6.7％(79/1191),x2=92.787,P=0.000].The incidence of brain injury for the newborns withobviousinflammatoryreactionwassignificantlyhigherthanthosewithout [(13.0％(26/200) vs 7.5％ (77/1025),x2=6.544,P=0.011].Severe infection was independent risk factor for severe brain injury by Logistic regression model analysis (OR =15.750,95％ CI:1.756-141.281,P=0.014).ConclusionsIniectious diseases could cause injury on central nervous system,especially when there are severe infections or inflammatory reactions. The severer the infection,the severer the brain injury,especially when complicated by some factors such as asphyxia and hypoglycemia.

Objective To explore risk factors of cerebral infarction in newborns by systematic reviews.Methods Case-control studies and case reports on risk factors of cerebral infarction in newborns from January 1997 to December 2011 were collected from database of CNKI,CQVIP,Wanfang Database,PubMed,OVID,Springer,Medline,Science Direct On Site,Besco and MD Consult.Meta analysis was performed on case-control studies with fixed or random effect model by Review Manager 5.0.Constitution ratio of risk factors of cerebral infarction in newborns in case reports was investigated.Results Two hundred and sixty-nine articles were found and among which,36 articles in English were selected for this study.Three case-control studies were found and adopted for meta analysis.Cumulative number of patients and control cases were 80 and 228,respectively.The pooled OR and 95 ％CI of selected factors were as follows:decreased fetal movement [7.10 (2.92-17.24)],abnormal fetal heart rate [4.45 (2.54-7.80)],vacuum delivery [2.99 (1.23-7.25)],resuscitation at birth [(3.14 (1.17-8.46)],premature rupture of membranes [2.40 (0.62-9.29)],cesarean section [2.64 (1.44-4.82)],preeclampsia [3.05 (1.44-6.43)],history of infertility [1.25 (0.18-8.67)],primiparous [1.79 (0.51-6.36)],oxytocin used [2.05 (0.99-4.25)],fetal growth restriction [0.99 (0.47-2.11)],meconium stained amniotic fluid [2.08 (0.94-4.58)],adverse pregnancy history [0.85 (0.43-1.68)] and breech presentation [0.38 (0.10-1.46)].Meta analysis showed that decreased fetal movement,abnormal fetal heart rate,vacuum extraction,resuscitation at birth,cesarean section and preeclampsia were risk factors of neonatal cerebral infarction.Decreased fetal movement,abnormal fetal heart rate and resuscitation at birth suggested that newborns suffered from perinatal hypoxia,vacuum extraction,cesarean section suggested abnormal delivery.It suggested that perinatal hypoxia and abnormal delivery were high risk factors of neonatal cerebral infarction.Among those factors,proportion of abnormal labor,fetal distress and hypercoagulabe state was 31.70％,21.13％ and 20.19％ respectively.Conclusions Abnormal birth,hypoxia,preeclampsia and hypercoagulation state might relate to neonatal cerebral infarction.

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.

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.

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.