Objective To establish the Valproate (VPA) exposure-induced autism spectrum disorder (ASD) model at early pregnancy in rats,and to study the changes of social interaction test and neuroimmune system in autism model rats,and discuss the pathogenic mechanism.Methods Twelve-week-old rats were randomly divided into the non-exposed group (n =10) and the VPA-exposed group (n =10).Their babies were respectively just the normal control group (n =10) and the model group (n =10).The autism-like social behavior was evaluated via the social interaction test.The level of interleukin (IL)-1β,IL-4,IL-6,interferon-gamma (IFN-γ),transforming growth factor-beta (TGF-β) in mothers and offspring were detected by using enzyme-linked immunosorbent assay (ELISA).The histopathological damage in brain was observed with immunohistochemical staining.Results The score of social interaction test in the model group [(-163.16 ± 101.92) scores]was lower than that in the normal control group [(132.73 ± 114.63) scores] (t =-6.100,P ＜ 0.05).The levels of IL-1β,IL-4,IL-6,IFN-γ in VPA-exposed group were higher than those in the non-exposed group (t =5.883,6.394,5.655,5.393,all P ＜ 0.05),while the level of TGF-β was lower than that in the non-exposed group (t =-6.726,P ＜ 0.05).The levels of IL-1β,IL-4,IL-6,IFN-γ in the model group were higher than those in the normal control group(t =3.058,3.048,6.670,5.486,all P ＜ 0.05),while the level of TGF-β was lower than that in the normal control group (t =-6.516,P ＜ 0.05).The change trend of the level of cytokines in the serum of ASD model rats was similar to the change trend of the level of cytokines in the serum of VPA exposed rats.The result of social interaction test the approach-avoidance score was inversely correlated with the levels of IL-1β and IL-4 (r =-0.802,-0.781,all P ＜ 0.05).The result of immunohistochemical staining showed the expressions of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA1) in the model group were higher than those in the normal control group.Conclusions The main neuroimmunological pathogenesis mechanism can be explained as follows:at early pregnancy,the maternal cytokines skewing influenced by VPA exposure can make immune activation,induce immune system dysfunction and affect the brain growth and development,which result in autism-like behavior in offspring.

Objective: To study morality and personality of children in single and non-single child family Method:204 children aged 4-14 in single child families were collected 204 children with siblings were sampled matched by age, sex, and education levels of parents and caregivers They composed the matched sample Other 2300 children were also collected in this study including 1626 in single child family and 674 with siblings (random sample) The research instruments included Inventory on Children's Morality, EPQ for children, and Scale of Children's Temperament Parents of children completed these inventory and scales; teachers of children completed the Inventory on Children's Morality Results:In the above two samples, in assessment of morality, parents of single child in family gave lower scores on their children's virtue than parents of multiple children gave on their children But no morality difference was found between single and non-single children when assessed by their teachers In the random sample, more school aged children in single child family had extroversive personality than their counterparts in multiple children family In the matched sample, no difference on introversive-extroversive between single and non-single children was found In both samples, there were more mood-stable and less unstable children in the group of children with siblings; types of Bile-plethora and Bile-melancholic were more frequent in children of single child family Conclusion:Children of single child family are unstable in mood, their morality problems are more obvious in family than in school

Objective To study the handicap of hearing and brain stem function in cerebral palsy children through determining their brainstem auditory evoked potential(BAEP).Methods BAEP were analyzed in 75 cases admissioned cerebral palsy children with MYTO type evoked potential equipment(made in Italy).Results The data showed that the abnormal BAEP rate was 72%(54/72),abnormity manifests as infaust differentiation of brainstem waves in diverse level,the latencies of wave Ⅰ,the interpeak latencies(IPLS) of wave Ⅰ～Ⅲ,Ⅲ～Ⅴ of BAEP in children with cerebral palsy were prolonged,the ratios of Ⅴ/Ⅰ wave amplitude was abnormal.Conclusion BAEP can be used to find out the changes of hearing handicap and brainstem function in children with cerebral palsy.

The animal model of cerebral palsy established using different high risk factors of cerebral palsy had pathologic changes in cerebral tissues and special behavior that similar to clinical manifestation of children with cerebral palsy. So animal model of cerebral palsy is a good tool to help study about human cerebral palsy. The authors mainly introduce the advance in research of selecting model animal and building method.

There are twenty-one gene-associated sites of hereditary spastic paraplegia (HSP) that have been reported, including eleve gene-associated sites of autosomal dominant inheritance, seven gene-associated sites of autosomal recessive and three gene-associated sites of X2 linked recessive. Nine genes of HSP have been cloned as followed, atlastin, spastin, paraplegin, L1CAM, PLP, Hsp60, maspardin, TRAK1 and so on.

Objective To discuss the main high-risk factors,clinical features and prognosis of global developmental delay(GDD),so as to provide effective basis for reducing incidence of children with GDD,early diagnosis,early intervention and improving prognosis.Methods One hundred and eighty-five cases of children with GDD,who were first diagnosed and treated in the Pediatric Neurology Rehabilitation Center,the First Affiliated Hospital of Anhui Medical University from October 2011 to September 2013,were included and high-risk factors,clinical features,and prognosis were analyzed.At the same time,the patients were followed up for 2 years and the children with abnormal development received continuous intervention and treatment during the follow-up.x2 test was used to compare high-risk factors and prognosis of different clinical features and Logistic regression models were selected to analyze high-risk factors influencing prognosis.Results In 185 cases with GDD,there were 119 children (64.3％) with motor and language developmental delay,which were the most common features,and followed by types of motor combined cognitive and language developmental delay which make up 30 cases (16.2％) and cognitive merged language developmental delay which make up 22 cases (11.9％) and the rarest type of 14 cases (7.6％) was motor and cognitive developmental delay.The main high-risk factors included neonatal asphyxia,premature birth,pathologic jaundice,intrauterine growth retardation,intrauterine hypoxia,neonatal hypoxic-ischemic encephalopathy (HIE),neonatal infection and pregnancy-induced hypertension syndrome and the differences of various clinical features with premature birth,intrauterine growth retardation,pathologic jaundice were statistically significant.Up to 2 years of follow-up,40 cases (21.6％) turned normal,but 145 children (78.4％) were still abnormal,including 97 children (52.5％) having significantly improved after intervention,30 cases(16.2％)of intellectual developmental disorder and 18 cases (9.7％) of cerebral palsy.The differences in various clinical features showed statistically significance (x2=60.960,P=0.017).The main high-risk factors affecting prognosis were intrauterine growth retardation [β=0.777,odds ratio (OR)=2.174],intrauterine hypoxia (β=0.706,OR=2.026),HIE(β=0.547,OR=1.729) and neonatal asphyxia (β=0.070,OR =1.073).Conclusion Causes of GDD are complex and prognosis is poor and the etiology and prognosis of children with different clinical features are also different.It is important to enhance perinatal care,early diagnosis and intervention for reducing the incidence of GDD and improving prognosis.

Objective Through modelling autism spectrum disorder(ASD) in condition of Poly-IC,to analyze the development,nervous pathological changes and behavior of rats in experiments,and to define whether the Sprague-Dawley(SD) rats are suitable for the study of ASD.Methods Ten SD rats were randomly divided in 2 groups with 5 rats in each group.The experimental group rats were injected intraperitoneally with 5 mg/kg Poly-IC at gestational day 12,while the rats in control group were injected intraperitoneally with 9 g/L normal saline at the gestational day 12.The body weight,eye-opening time,swimming performance,and conduct parallel water maze test,social communication ability test of each offspring were recorded,and the developmental state of rats and the existence of autism-like social behavior were evaluated.The alterations in hippocampus morphology of offspring rats were indirectly observed with immunofluorescence double standard dyeing.Results Compared with the control group,the weights of the experimental rats were lighter,opening-eye time was delayed,swimming score was lower,in each measurement point.The differences above all were significant(all P ＜0.05).The near-escape scores of experiment rats in social communication ability test were lower than those of rats in control group.The rats in the experimental group needed more time to get the Morris water maze platform,and the times of rightly run through the Morris water maze decreased significantly,and the differences were significant (all P ＜ 0.05).Pathological results revealed that the mineralocorticoid receptor (MR) average optical density value (0.061 3 ± 0.028 8) and the glucocorticoid receptor (GR) mean optical density value (0.041 9 ± 0.040 3) in hippocampal CA1 area of experiment rats were lower than those of the control group (MR:0.081 3 ±0.053 9;GR:0.061 2 ±0.043 6) (t =10.319,10.241;all P ＜0.05).There was no significant difference between MR/GR ratio(the ratio of MR and GR optical density value in the same vision area) in experimental group and in the control group.Conclusions The Poly-IC during early pregnancy can cause lag behind in motor development,harm the social communication ability,lose memory ability to learn,and develop ASD symptoms of SD rat,and these symptoms may be associated with abnormal expression of MR and GR on the hippo-camp cells surface.AS a consequence,early pregnant SD rats exposed to Poly-IC can be used for the establishment of the model of ASD which can provide a platform for the research of ASD.

Therearemanywaystoestablishanimalmodelsofneonatalhyperbilirubinemia,suchasintraperitoneal or intravenous injection , genetic defect animal models , the use of chemical drugs , and injection of bilirubin into cerebellomedullary cistern , and so on . In order to study the etiology , pathogenesis , and therapy of neonatal hyperbilirubinemia through animal models , we review the literature on rodent and primate models of neonatal hyperbilirubinemia ,including establishment of models and their applications , in order to provide reference for the research of neonatal hyperbilirubinemia .

Objective To investigate the influence of primary cultured neonatal rat hippocampal neurons caused by human cytomegalovirus (HCMV AD169) infection on intracellular calcium and its mechanism.Methods Twenty SPF SD rats born within 24 hours(10 cases of male and 10 cases of female) were assigned to establish the primary rat hippocampal neuronal monolayer cells; After cultured 8 days in vitro,the eligible cells were randomly divided into HCMV infection group,HCMV + MK-801 group,MK-801 group and control group,with 10 wells in each group.The fluorescence intensity values of the intracellular free calcium were detected after 24 hours of treatment with Fluo-3AM fluorescence staining.Results Inoculation of HCMV neurons after 24 h turned to round and swollen gradually,and 4days later,most of the cells disappeared; by immunohistochemistry in cultures of hippocampal neurons in HCMV,visible early proteins,brownish yellow granules,hematoxylin were found after being stained with brown pigment.The fluorescence intensity values of neuronal intracellular calcium (215.5 ± 14.9) in HCMV group was higher than that of control group (116.4 ± 5.9) (t =15.2,P ＜ 0.01),whilerise,that in MK-801 group (88.1 ± 4.5) was significantly lower than that of control group,with decreased rate of (24.0 ± 6.7) ％ (t =-9.3,P ＜ 0.01).The fluorescence intensity values of neuronal intracellular calcium in HCMV + MK-801 group (135.5 ± 8.6) was significantly decreased compared with that of HCMV group (215.5 ± 14.9),with decreased rate of (37.0 ± 3.4) ％ (t =11.3,P ＜ 0.01).Conclusions Intracellular calcium overload of cultured rat hippocampal neurons in vitro with HCMV AD16 strains infection can be detected.One of its main mechanisms is the N-methyl-D-aspartic acid receptor channel-mediated calcium influx.

Objective To establish and evaluate a reliable and highly reproducible neonatal rat model of hyper-bilirubinemia and to provide an experimental basis for research of kernicterus and related mechanism of neuroinjury.Meth-ods Sixty 7-day old SD rats (28 male and 32 female) were used in this study.Three doses of phenylhydrazine hydrochlo-ride (25, 50, and 75 mg/kg) were intraperitoneally injected respectively to the neonatal rats to establish models of hyper-bilirubinemia induced by hemolysis.The control group was set up at the same time.48 hours after the experimental treat-ment, the bilirubin in blood and brain tissue, neuron-specific enolase (NSE) of brain tissue, and hemoglobin were detec-ted to evaluate the models.Results Compared with the control group, the bilirubin in the blood and brain tissue and the brain tissue NSE in the three experimental groups were significantly higher than that in the control group (P<0.05), while hemoglobin content was significantly lower than that in the control group (P<0.05).The bilirubin of blood and brain tis-sue and brain tissue NSE in the 50 mg/kg and 75 mg/kg dose phenylhydrazine hydrochloride groups were significantly high-er than that of the 25 mg/kg dose group ( P<0.05) , while hemoglobin content was significantly lower than that of the 25 mg/kg dose group ( P<0.05 ) .There were no significant differences between the 50 mg and 75 mg dose groups ( P>0.05).Conclusions Intraperitoneal injection of phenylhydrazine hydrochloride can be used to produce neonatal rat mod-els of hyperbilirubinemia, mimicking the clinical features of this disease, and 50 mg/kg of phenylhydrazine hydrochloride is the best concentration.It is an ideal method to establish newborn rat models of hyperbilirubinemia.