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Special Topic and Discussion

Original Papers

  • The validation of the classification criterion of waist and waist-to-height ratio for cardiometabolic risk factors in Chinese school-age children
  • MENG Ling-hui,MI Jie
  • 2008 Vol. 3 (5): 324-332. DOI:
  • Abstract ( 3886 ) PDF (1355KB)( 3795 )
  • Abstract Objective To restudy and identify the cutoffs for waist circumference and waist-to-height ratio that indicate increased risk of cardiovascular risk factors and their clustering that would be consistent with central adiposity in Chinese school-age children.Methods The author of this paper had brought forward 80th percentile of waist circumference by age and gender and waist-to-height ratio equal to 0.46 as the primary cutoffs of school-age children and adolescents central adiposity in the BCAMS study, which was a cross-sectional representative population based survey on Metabolic Syndrome for Children and Adolescents in Beijing. But the cardiovascular risk factors results were based on the finger-stick capillary test in that study. This time a total of 3 525 schoolage children aged 6-18 years were recruited from the BCAMS study. 1 454 schoolchildren aged 7-18 years were recruited from 8 schools in district of Haidian in Beijing. Data of anthropometric measures including weight, height, waist circumference and blood pressure were collected. Venous blood samples were obtained after a 12-hour fast, and the levels of fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoproteincholesterol (HDL-C) were measured. In this study high blood pressure (HBP) was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥95 th percentile for age and gender of schoolchildren in Beijing in 2004. Impaired fasting glucose (IFG) was diagnosed according to updated ADA standard of USA (2005, FG≥5.6 mmol·L-1), blood levels of TG≥1.7 mmol·L-1, blood levels of TC≥5.2 mmol·L-1, HDLC≤1.03 mmol·L-1 were defined as raised TG, raised TC and Low HDLC, respectively. For the 1 454 recruited children in Haidian, liver were tested by ultrasonographic, and abnormal hepatic sonograms were diagnosed additionally. Elevated glutamatepyruvate transaminase was diagnosed by ALT≥40.0 U·L-1 and elevated glutamicoxalacetic transaminase was determined by AST≥45.0 U·L-1. Nonalcoholic fatty liver was diagnosed according to the diagnostic criteria of nonalcoholic fatty liver disease recommended by the Fatty Liver and Alcoholic Liver Disease Study Group of Chinese Liver Disease Association. 70 th, 75 th, 80 th, 85 th, 90 th and 95 th percentiles by gender and age for WC, WHtR equal to 0.42, 0.44, 0.46, 0.48, 0.50 and 0.52 were selected as temporary criterions based on primary screening cutoffs brought forward in the last paper of the author. Statistic methods included the followings, measurement data were expressed by mean and standard deviation and analyzed with independent sample t-test, categorical data were compared with chisquare analyze, analysis of covariance adjusted by gender, age and puberty status was used to compare the level of cardiovascularity in stratification, and classical screening study. A probability level of P < 0.05 was used to indicate statistical significance.ResultsMean BMI, systolic blood pressure, diastolic blood pressure, triglyceride and total cholesterol levels were incrementally higher and mean HDL-cholesterol values were incrementally lower with each unit increase in waist circumference and waist-to-height ratio. And the abnormal rates of the cardiovascular risk factors and their clustering increased with WC and WHtR. Both the points at which sensitivity and specificity were equally perfect at sex, agespecified 85th percentile of waist circumference and a waist-to-height ratio of 0.48 optimal cutoffs. At those points positive predictive value and negative predictive value were all optimal.Conclusions Cutoffs of waist circumference at 85th percentile by age and gender and waist-to-height ratio equal to 0.48 are needed in the identification of Chinese school-age children and adolescents at high risk of cardiovascular risk factors and their clustering.

  • Expression and distribution of glial cell derived neurotrophic factor, interstitial cells of Cajal and Connexin 43 in Hirschsprung′s disease
  • WANG Bao-xi, HOU Yu, YANG Ye
  • 2008 Vol. 3 (5): 333-339. DOI:
  • Abstract ( 2337 ) PDF (3745KB)( 2829 )
  • Abstract Objective To investigate the relationship between the gene expression of GDNF and the distribution of interstitial cells of Cajal(ICC),Connexin 43(Cx43) and the mechanism of development of Hirschsprung′s disease (HD). Methods Fortytwo pairs of full thickness specimens(aganglionic segments and ganglionic segments)were from Hirschsprung′s disease patients diagnosed pathologically, immediately after operation. Another five colon specimens were obtained from intussusception patients as control.The GDNF mRNA expression and the distribution of ICC,Cx43 were detected in different parts of HD segments.Results ①GDNF mRNA expression in the aganglionic segments were decreased, compared with the ganglionic segments and the control group(P<0.05〉.There were no statistical differences in GDNF mRNA expression between control group and the ganglionic segments group. Of all the aganglionic segments group, GDNF mRNA expression in short segment aganglionosis group were less than that in long segmenttype Hirschsprung′s disease group(P<0.05)。There were no statistical differences of GDNF mRNA expression in dilated segment between long segmenttype and short segmenttype group. ②ICC were mainly distributed in submucosal plexus (ICSM) and myenteric plexus (ICMY) of the distal colon, and also distributed in circular muscle layer and longitudinal muscle layer (ICIM). ICMY were distributed continuously between the circular and longitudinal muscle layers and formed a network;(2).In the segments of HD,ICC were decreased obviously in aganglionic segments group (P<0.001)compared with the control group. The ICMY network was disappeared, and the configuration of the residual ICC was abnormal. In the transitional zone group, ICC were reduced than those of ganglionic segments group and the control group(P<0.05), but were more than those of the aganglionic segments group (P<0.001). Their configuration was close to normal,but the ICMY did not form a normal network. There was no difference in the distribution of ICC between ganglionic segments group and the control group (P>0.05).③There was no immunoreactivity of Cx43 in the muscle layers of aganglionic segment in HD,which had significant difference in Cx43 expression between ganglionic segment of HD and normal bowels.Moderate immunostainning of Cx43 was observed at the circular muscle and the region between the circular and longitudinal layer in migratory segment from patients with HD,which had significant difference in Cx43 expression between ganglionic and aganglionic segment of HD.Moderate to strong immunostainning of Cx43 was observed at the circular muscle and the region between the circular and longitudinal layer in ganglionic segment from patients with HD and in normal bowels.There was no significant difference in Cx43 expression between ganglionic segment of HD and normal bowels.Conclusions The abnormal expression of GDNF mRNA, the decrease and paramorphia of ICC , the lack of expression of Cx43 in the aganglionic bowel of HD and the destruction of the gap junction indicated that the impaired intercellular substance exchange.The disorder of intercellular communication between cells might partly be responsible for the motility dysfunction in HD.

  • Molecular epidemiology of norovirus infection in hospitalized children with diarrhea in partial areas of Shanghai, China, 2001-2005
  • XU Jin, SUN Jia-e, DING Yun-zhen, SU Li-yun, YANG Yi
  • 2008 Vol. 3 (5): 340-344. DOI:
  • Abstract ( 3726 ) PDF (1287KB)( 3394 )
  • Abstract Objective As a genus of human calicivirus, norovirus has been recognized as the most common cause of foodborne and nosocomial outbreaks of acute nonbacterial gastroenteritis in humans worldwide and the secondly important pathogen for viral diarrhea in hospitalized children. The aim of the present study was to evaluate the prevalence of norovirus in hospitalized children under 5 years old with acute gastroenteritis in the biggest pediatric hospital in Shanghai, China over a long period. The information will provide important data and theoretical basis for development of norovirus vaccine and control of norovirus infection.Methods A total of 5 534 stool samples were collected from hospitalized children with acute diarrhea in children's hospital, Fudan University during 2001 to 2005. 96% of the samples were collected within 5 days after illness onset. After all the samples were tested for rotavirus antigen, systematic sampling was applied to collect 484 samples from all the rotavirus negative stools. RNA was purified from 10% (W/V) of fecal suspensions using TRIzol. RT-PCR was applied for determination of norovirus. A multiple sequence alignment of 170nt nucleotide sequence from region B of the polymerase region sequence was constructed using Clustal W. Phylogenetic trees were constructed using Mega 4.1 software by the neighborjoining methods. Results Of the 45 norovirus infected children, more than onethird (35.6%) were at 6-11 months of age, followed by 12-23 months (22.2%) and 0-5 months (20%). The monthly distribution of norovirus infection illustrated a seasonal peak from August (17%) to November (9.8%). Another small peak was found in May and June. Among the 6 norovirus positive samples in 2001, 2 were identified to be GⅡ-7, one was GⅡ-3 and the other 3 strains were GⅡ-4 genotype. 1 sample belonged to GⅡ-3 and the other 3 were GⅡ-4 in the years of 2002. All the 27 samples during the years of 2003 to 2005 were identified to be GⅡ-4 genotype.Conclusions A seasonal and age distribution of norovirus infections was found in hospitalized children in Shanghai. GⅡ-4 was the most predominant genocluster circulating in the 5 years. Our findings will provide useful data for prevention of norovirus diseases in children in Shanghai.

  • Preliminary study on the activities of terminal ileum mucosal brush border peptidase and disaccharidase in children with persistent diarrhea and chronic diarrhea
  • YE Li-ping, GONG Si-tang,OU Wen-ji, HUANG Hai, HE Wan-er, PAN Rui-fang, GENG Lan-lan, CHEN Pei-yu, LIU Li-ying, CHEN Bao-xin, HUO Xiao-he, WANG Feng-hua, ZHENG Xiu-xia
  • 2008 Vol. 3 (5): 345-349. DOI:
  • Abstract ( 3263 ) PDF (932KB)( 3077 )
  • bstract Objective To investigate the changes of terminal ileum brush border peptidase and disaccharidase activities in persistent diarrhea and chronic diarrhea children. To investigate the relationship between ileum mucosal histology and the ileal brush border peptidase and disaccharidase activities.Methods The terminal ileal mucosal specimens were collected from children who were taken enteroscopy during July 2007 to March 2008 in our hospital.Two ileal mucosal specimens were obtained from the terminal ileum endoscopically. One was stored intact at -80℃ for assaying of brush border peptidases and disaccharidase activities,and another was placed in 10% formalin for histologic examination. All children were divided into two groups, persisting diarrhea and chronic diarrhea group and nondiarrhea group. The terminal ileal mucosal histologic changes were graded according to the Marsh classification as follows: normal villus, mild villous atrophy, moderate villous atrophy and severe villus atrophy. If there was no villous atrophy, they were classified into two groups according to McHugh : normal terminal ileum mucosa and chronically inflamed terminal ileum mucosa. The ileal brush border peptidase and disaccharidase activities of persistent diarrhea and chronic diarrhea group were compared to nondiarrhea group with normal mucosa. Protein concentrations in homogenates were determined according to the method of BCA. Enzyme activities in homogenates were expressed as international units per gram of protein .One unit corresponded to the hydrolysis of 1 μmol of substrate per minute under the assay conditions. All data were analyzed by SPSS version 14.The normality of brush border disaccharidases activities were determined by KolmogorovSmirnov test, if the data were not normally distributed, a logarithmic transformation was performed to normalize the data. All the results were represented as mean±standard deviation. Differences between groups were determined by twogroup ttest, P values <0.05 was considered to be significant.Results Terminal ileal mucosal specimens were collected from 27 children, 12 chilidren were persistent diarrhea and chronic diarrheas. Fifteen children were nondiarrhea group who accepted colonoscopy owing to the gastrointestinal symptoms such as hemafecia,abdominal pain, swollen, polypus, pale, etc. Of the 27 children,20 were boys and 7 were girls(2.86∶1). Ages ranged from 1 to 12 years (mean age, 5 years).All ileal mucosal villi were normal, but there were 17 children with normal terminal ileum mucosa and 10 children with chronically inflamed terminal ileum mucosa. In the diarrhea group, there were 6 children with normal mucosa and 6 children with chronically inflamed mucosa.In other disease group, there were 11 children with normal mucosa and 4 children with chronically inflamed mucosa. No differences statistically in ileum peptidase and disaccharidases activity values were observed between diarrhea group and control group. No differences statistically in ileum brush border peptidase and disaccharidases activity values were observed between normal terminal ileum mucosa and chronically inflamed terminal ileum mucosa. Conclusions The level of ileal mucosa peptidase and disaccharidases activities were not changes in persistent diarrhea and chronic diarrhea children with normal villi. There were no obvious changes in the level of peptidase and disaccharidases activities in chronically inflamed terminal ileum mucosa if the villus was normal.

  • Clinicopathological characteristics and prognosis of embryonal rhabdomyosarcoma of the head in children
  • LIN Lan, WANG Shu-yi, WANG Jian
  • 2008 Vol. 3 (5): 350-355. DOI:
  • Abstract ( 2536 ) PDF (3876KB)( 2684 )
  • Abstract Objective Embryonal rhabdomyosarcoma(ERMS) is probably the most common sarcoma arising in the head and neck in children. The clinical behavior of this particular rhabdomyosarcoma is known to be highly aggressive, and its eventual outcome is dismal. Our purpose was to study the clinicopathological characteristics and to discuss the correlation of clinicopathological features of ERMS and prognosis.Methods We conducted a retrospective study of children diagnosed for embryonal rhabdomyosarcoma of the head and neck at EENT Hospital of Fudan University between the years 2004 and 2007 in accordance with the diagnostic criteria of International Academy of Pathology(IAP 2002) and botryoid rhabdomyosarcoma(BERMS) was included in ERMS.The tumours were staged according to the Intergroup Rhabdomyosarcoma Study. The clinical, pathological and immunohistochemical features of 18 cases of embryonal rhabdomyosarcoma were evaluated.Results There were 12 boys and 6 girls, aged from 5 months to 18 years,among them,12 cases were younger than 10 years. Clinically, most patients presented with a mass in the mouth,nose or ear regions and symptoms were related to tumor invasion ,such as nasal obstruction,trachyphonia and facial paralysis. Seven cases belonged to stage Ⅰ-Ⅱ ,while 11 cases were in stage Ⅲ-Ⅳ. CT scan or MRI usually showed a soft tissue tumor with expansive growth, associated with bone erosion or destruction. Before surgery, 5 cases were misdiagnosed as benign lesions. They were polyps,inflammation mass,nasopharyngeal angiofibroma,cholesteatoma and tympanic paraganglioma respectively. Histologically, the tumors consisted of a variable admixture of undifferentiated and differentiated cells (rhabdomyoblasts). Among them, 4 cases belonged to the botryoid variant which typically had a cambium layer. The tumor was totally or subtotally removed in 5 cases, partially removed in 2 cases, and biopsied only in 11 cases. Followup information of 10 patients showed 4 cases died of diseases belonged to stage Ⅲ, and 6 cases alived without disease adopted multimodal therapy with combination of surgery,chemotherapy and radiation.Conclusions Embryonal rhabdomyosarcoma of the head in children is a highly malignant tumor which grows quickly. In early stage, it may be misdiagnosed. Early and precise diagnosis and combined management is crucial to improve the survival rate.

  • Analysis of the laboratory study indices based on the epidemiological data of the children with Kawasaki disease in Beijing in six years
  • Beijing Kawasaki Disease Cooperative Research Group:LU Wei-hui,DU Zhong-dong,ZHAO Di,DU Jun-bao,LU Shan,YAN Zong-rong,YI Jing-mei,HOU An-cun,ZHOU Zhong-shu,DING Guo-fang
  • 2008 Vol. 3 (5): 356-361. DOI:
  • Abstract ( 3413 ) PDF (593KB)( 3064 )
  • Abstract Objective Up to now, there has been no gold test for the diagnosis of Kawasaki disease (KD). Some children might present as incomplete KD. This study sought to perform a statistical description for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count (PLT), plasma albumin (ALB), alanine transaminase (ALT), hemoglobin (Hb), leukocyte count (WBC) and discuss the relationships among these laboratory indices and coronary ectasia and KD nonresponder, respectively.Methods A questionnaire form and the 5th revised diagnostic guideline for KD were sent to all hospitals with pediatric inpatient beds in Beijing and its suburbs. According to the diagnostic criteria of KD, all hospitalizations for patients less than 18 years of age with KD were included. The laboratory examination indices of patients with KD hospitalized during the years 2000 to 2005 were recorded and statistically described. ESR>20 mm·h-1,CRP>8 mg·dL-1,PLT >300×109·L-1,ALB<30 mg·L-1,ALT>40 U·L-1,Hb<110 g·L-1,WBC>10×109·L-1 were defined as abnormal. The differences among the abnormal rates of ESR, CRP, PLT, ALB, ALT, Hb and various ages were evaluated by chisquare test. Patients were divided into two groups, one without coronary complications, the other with coronary artery dilation or aneurysm. The laboratroy indexes were coded by their severity. Chi-square test and non-conditional logistic regression were used to estimate the relationship between these lab indexes and coronary artery lesion. Patients were further divided into IVIG refractory group and IVIG response group. Chisquare test and nonconditional logistic regression were used to estimate the relationship between these lab indexes and IVIG refractory KD. Results Totally 1 335 children with KD were enrolled, including 868 boys and 467 girls, with the ratio of 1.86:1. Their ages varied from 1 month to 13 years (92.9% were younger than 5 years old). The incidences of elevated ESR, CRP, PLT, WBC and lower ALB, Hb abnormalities in KD were 96.0%, 90.0%, 92.2%, 80.4% and 45.7%, 48.8%. ESR varied from 2 to 160 mm·h-1 (mean 80.01 mm·h-1). CRP varied from <0.06 mg·dL-1 to 433 mg·dL-1 (mean 77.83 mg·dL-1). PLT varied from 127 to 1 456×109·L-1(mean 556.1×109·L-1). ALB varied from 12-55 mg·L-1(mean 31.36 mg·L-1). Hb varied from 58-184 g·L-1(mean 111.33 g·L-1). WBC varied from 3.2×109-63.3×109·L-1(mean 15.7×109·L-1). Pearson chi-square test showed that the abnormal rate of Hb was related with age, lower Hb and ALB were related with CAL, higher CRP, ALT, WBC and lower ALB, Hb were related with KD nonresponders (P﹤0.05). Logistic regression analysis found ALB(B=0.301,P=0.02,95%CI:1.049-1.742), Hb(B=-0.210,P=0.001,95% CI:0.719-0.913) were related with coronary impairment and CRP(B=0.193,P=0.018,95%CI:1.034-1.422), WBC(B=0.353,P﹤0.000 1,95%CI:1.170-1.731), Hb(B=-0.330,P﹤0.000 1,95%CI:0.627-0.825), ALT(B=0.460,P=0.001,95%CI:1.204-2.085) were related with IVIG non-responders(P﹤0.05).Conclusions The incidences of more than 90% ESR, CRP, PLT, and WBC elevation were seen in acute KD, which might be helpful for the diagnosis of acute KD. Younger KD patients had more possibility of anemia. Physicians should pay more attention to KD patients with lower ALB and Hb levels to prevent coronary impairment. KD patients with CRP,ALT and WBC elevation, Hb decrease should be taken care of IVIG nonresponders.

  • Evaluation of the efficacy of physio-psychological treatment for primary nocturnal enuresis and its follow-up in children
  • MA Jun, JIN Xing-ming, ZHANG Yi-wen, WU Hong, JIANG Fan
  • 2008 Vol. 3 (5): 362-367. DOI:
  • Abstract ( 2645 ) PDF (875KB)( 2733 )
  • Abstract Objective To Study the clinical longterm efficacy of physiopsychological treatment in children with primary nocturnal enuresis(PNE) and analyze the mechanism of this treatment.Methods The study objects were 68 children who were diagnosed as primary nocturnal enuresis(PNE) and applied physiopsychological treatment in the Department of Developmental and Behavioral Pediatrics of Shanghai Children's Medical Center from September 2003 to January 2006, including 41 boys and 27 girls; The age range was from 5 to 16 years, mean age was (8.28±2.01) years. PNE diagnosis strictly followed International Classification of Diseases, the 10th edition (ICD10). The clinical data were analysed retrospectively including general conditions, clinical manifestations, clinical history, birth history, developmental and behavioral history, family history, psychological and social environments, outcomes of psychological tests(including Achenbach children behavioral checklist, Wechsler intelligence scale for childrenRevised, Wechsler preschool and primary scale of intelligence), ultrasonic graph of bladder capacity(before and after treatment), outcomes of laboratory tests(such as urine routine, nocturnal urine specific gravity, x-ray graph of lumbar and sacral vertebrae, ultrasonic graph of urinary system etc.), diagnosis, treatment procedure, the change in bedwetting frequency, frequency of getting up for urination by themselves at night just responding to the sense of full bladder. All patients were followed up 6 months after stopping treatment. During treatment period, they were followed up per 2 weeks. After stopping treatment, they were followed up every 1 month. The longterm efficacy of physiopsychological treatment was calculated. Logistic-multi-factor-analysis was applied to find out the risk factors that influenced clinical efficacy of physio-psychological treatment.Results The longterm efficacy of physiopsychological treatment in 68 children with PNE during this period was just as follows: 43(63.2%)were cured,18(26.5%)significantely improved,5(7.4%)partially improved,2(2.9%)not improved. The average frequency of enuretic onsets before treatment was (6.12±1.32) times per week,while the average frequency of enuretic onsets 6 months after treatment was (1.23±0.18) times per week (t= 2.65,P=0.011 )。The average frequency of getting up by themselves at night responding to the sense of full bladder before treatment was (0.72±0.15) times per week,while the average frequency of getting up by themselves at night responding to the sense of full bladder 6 months after treatment was (6.83±1.16) times per week (t= 2.25,P=0.026 ).The bladder capacity/body weight before treatment was (4.13±0.98) mL·kg-1,while the bladder capacity/body weight after treatment was (8.69±1.96) mL·kg-1(t= 2.58,P=0.016). Logistic regression analysis showed the risk factors that decreased longterm efficacy of physio-psychological treatment were patients younger than 8 years(RR=3.24,95%CI:2.54-4.83),comorbided other behavioral problems(RR=2.95,95%CI:1.33-4.16),less than 5 mL·kg-1 of the bladder capacity(RR=1.75,95%CI:1.03-2.67),never getting up by themselves at night responding to the sense of full bladderbefore treatment(RR=1.25,95%CI:1.04-2.17).Conclusions It could be relatively soon to develop children's ability to control the bladder at night when the physio-psychological treatment was applied to children with PNE. Moreover, the bladder capacity was increased during this treatment period. So the longterm efficacy was ensured.

  • A study of inhibition on expression of VEGF by antisense oligonucleotides and its biological effect on LA-N-5 cells
  • YU Fang, TANG Suo-qin, FENG Chen, YIN Hua, CAI Zheng-ju
  • 2008 Vol. 3 (5): 368-373. DOI:
  • Abstract ( 2717 ) PDF (1247KB)( 2643 )
  • Abstract ObjectiveT o investigate if VEGF ASODN transfection to LA-N-5 cells inhibits VEGF mRNA expression, thus affects its differentiation and proliferation.Methods LA-N-5 cells were transfected with VEGF ASODN or MSODN alone, ordelivered by LipofectamineTM2000, respectively, VEGF mRNA pre- and post transfection expression was detected by semi-quantitative RT-PCR, MTT was employed for evaluation of differentiation and proliferation of cells in each group.Results ①The semiquantitative RT-PCR detection showed VEGF165 and VEGF121 mRNA expression were of 0.275±0.035, and 0.165±0.017 respectively in group of ASODN+LipofectamineTM2000, compared to 0.346±0.029 and 0.227±0.036 respectively in group of ASODN, after 72 hours.VEGF mRNA expression in groups of ASODN and ASODN+ LipofectamineTM2000 were significantly inhibited and the inhibition with ASODN+LipofectamineTM2000 was more significant compared with that in ASODN (P<0.05).②MTT assay at 0,12, 24, 36, 48, 60, and 72 hours after transfection showed that cellular proliferation was significantly inhibited in the groups of ASODN and ASODN+LipofectamineTM2000.After 48 hours the inhibition rate reached (39.92±2.74)% and(55.80±2.52)%, especially in later group, the inhibition was more significant than that in ASODN group(t=-12.065,P=0.00, P<0.05). The growth and proliferation of LA-N-5 cells in groups of MSODN and MSODN+ LipofectamineTM2000 did not show any difference compared to control group(P>0.05).Conclusions VEGF ASODN is capable of suppressing VEGF mRNA expression and cellular proliferation in LA-N-5 cells, and LipofectamineTM2000 can significantly strengthen this inhibition.

  • Genomic and bioinformatics analysis of the subventricular zone in 3-day old rats after ischemia
  • GAO Yan-yan,SUN Jin-qiao,SHA Bin,YANG Yi,YAO Ming-zhu,SHAO Xiao-mei,ZHOU Wen-hao
  • 2008 Vol. 3 (5): 374-380. DOI:
  • Abstract ( 3042 ) PDF (2410KB)( 2889 )
  • Abstract Objective As the largest pool of neural stem cells in mammalian animals, the subventricular zone (SVZ) persists through lifetime and retains the potency of selfrenewing, cell proliferation and differentiation. After brain ischemia, this potency can be recaptured and neurogenesis be accomplished, which provides a potentially significant therapeutic strategy for ischemic injury not only in adult brain but also in premature brain. A specialized milieu supports neurogenesis and regeneration after injury in SVZ. Stem cells frequently reside in niches that regulate their selfrenewal, activation and differentiation. Understanding the molecular component changes after ischemia in neural stem cell niche is crucial to delineating the function of neural stem cells and ultimately their therapeutic potential.Methods To investigate the effect of brain ischemia on premature SVZ, 3-day old SpragueDawley rats were employed, both bilateral carotid arteries were occluded for experimental group and rats with unoccluded arteries were used as the control group and animals were killed at the chosen time point: 1 day, 4 days and 7days after surgery. After SVZ culture was isolated,RNA was extracted and processed, microarrays containing approximately 28 000 known genes were applied to get the data about gene expression changes, and three methods were used to analyze this data bulk: differential expression analysis, cluster analysis based on time series and gene regulatory network based on function similarity . The expression of TGF-β1 and its downstream protein Smad2 were certificated by RealTime PCR.Results ① By differential expression analysis, 17 genes were found to be changed in SVZ niche after ischemia, among them, 10 were up-regulated and 7 were down-regulated. These genes were associated with multiple functions including signal transduction, inflammation and cellular structure, etc.②By cluster analysis based on time series, TGF-β among all the genes participating in cell proliferation and apoptosis, was found to take an important role in the gene expression changes. It was found that both TGF-β1 and Smad2 mRNA increased at each of three time points, and the peak increase occurred at 7 days after the ischemic injury.③In the gene network based on function similarity composed of all the genes in Wnt, TGF, BMP and VEGF pathways, 13 were found to act as the hinges.Conclusions The crosstalk of Wnt, TGF, BMP and VEGF pathways was likely to constitute a part of the key regulators among all the genes participated in the premature SVZ niche change after ischemic injury, these genes functioned at different levels in signal pathways in synergism or antagonism.TGF-β1 may be play an important role in immature brain after ischemia through activating neural stem cell proliferation and differentiation.

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