Novel Variants in the FIG4 Gene Associated With Chinese Sporadic Amyotrophic Lateral Sclerosis With Slow Progression

Background@#and Purpose Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. @*Methods@#All 23 exons of FIG4 were sequenced using targeted next-generation sequencing.An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. @*Results@#No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale–Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. @*Conclusions@#Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.

Association of interleukin-10 gene-592C/A polymorphism with concentration of interleukin-10 in children with bronchial asthma / 中华实用儿科临床杂志

Objective To explore the polymorphism of-592C/A of IL-10 gene promoter region in children with bronchial asthma and its relationship with serum concentration of IL-10.Methods Ninety-two children with bronchial asthma and 92 healthy children were selected for study,polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used for the analysis of-592C/A of IL-10 promoter region polymorphism.The frequencies of genotypes of IL-10 gene-592 locus (CC,CA and AA) and alleles were accounted respectively,and x2 test was used to analyze the difference between the groups.Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of the serum IL-10,and F test and q test were used for statistical analysis.Results Compared with the healthy control group,there were significant differences in-592C/A polymorphism of IL-10 gene in asthma group.The frequencies of AA genotypes (56.5％) and A allele (73.9％) in asthma group were higher than those (34.8％,58.7％)in the control group,there were significant differences(x2 =9.32,P ＜ 0.01 ;x2 =8.87,P ＜ 0.005,respectively).The individuals with AA genotype and A allele were 3.25 (95 ％ CI:1.28-8.28,P ＜ 0.05) and 1.99 (95 ％ CI:1.28-3.08,P ＜0.01) times susceptible to asthma compared with CC genotype and C allele.The serum concentration of IL-10 in asthma group was significantly lower than that in healthy control group,whether in attacking-stage or remission-stage,and there were significant differences (all P ＜ 0.01).The individuals with AA genotypes had lower serum IL-10 concentration than those with CC genotypes (P ＜ 0.05) . Conclusions The IL-10 gene-592C/A polymorphism is different significantly between children with bronchial asthma and healthy ones,and this polymorphism influences the concentration of IL-10.The individuals with AA genotype have relatively lower IL-10 concentration,and A allele may be one of genetic susceptibility factor of bronchial asthma in children.

Effect of hyperbaric oxygen on the expression of nitric oxide synthase mRNA in cortex after acute traumatic cerebral injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of hyperbaric oxygen (HBO) treatment on the expression of nitric oxide synthase (NOS) mRNA in cortex after acute traumatic cerebral injury, and to study the mechanism of HBO on brain injury.</p><p><b>METHODS</b>Acute traumatic brain injury model was established with rest received free fall injury method in SD rats. 0.25 MPa HBO treatment was used 1 h or 12 h after brain injury and the cortex was isolated 6 h or 24 h after brain injury respectively. The expression of mRNA coding for nNOS, eNOS or iNOS were assayed using reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The expression of nNOS, eNOS and iNOS mRNA were significantly decreased in 0.25 MPa HBO treatment groups than those in acute cerebral injury groups (P < 0.01). The amount of nNOS, eNOS and iNOS mRNA was significantly lower in HBOT 24 h group than those in HBOT 6 h group (P < 0.05, P < 0.01). There was no significantly difference among nNOS, eNOS and iNOS mRNA in 0.25 MPa normoxic hyperbaric nitrogen groups and acute cerebral injury groups (P > 0.05).</p><p><b>CONCLUSION</b>HBO may exert significant effects on the expression of nNOS mRNA/iNOS mRNA and protect cortical neuronal from traumatic cerebral injury.</p>

Risk factors for Tourette syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To identify the risk factors for Tourette syndrome (TS) in children.</p><p><b>METHODS</b>Through a genetic epidemiologic case control study, segregation ratio was estimated using the method of Li-Manted-Gart in 80 children with TS. Heritability for the first- and second-degree relatives was estimated using the Falconer regression method. In addition, the 80 children and 80 controls with other diseases were evaluated using the Family Environment Scale and a self-designed questionnaire. Risk factors for TS were investigated using single factor and multifactor regression analysis.</p><p><b>RESULTS</b>The segregation ratio of TS was 0.1176. Heritabilities for the first- and second-degree relatives were (49.7±2.6)% and (21.5±3.4)% respectively. The weighted mean heritability of the first-degree and second-degree relatives was (39.5±2.1)%. Significantly decreased scores were noted in independence, active-recreational orientation and organization and increased scores were noted in the conflict and control in the TS group compared with the control group (P<0.01). Single factor analysis indicated that the risk factors for TS included family history, type of home education, maternal smoking, family conflict, low level of parental education, family control and fetal anoxia. Multifactor regression analysis indicated that there were five important risk factors for TS: family history, family conflict, type of family education, low level of parental education and maternal smoking.</p><p><b>CONCLUSIONS</b>Both heredity and environment are involved in the pathogenesis of TS. The mode of inheritance for TS is polygenic. Improving the living environments of children with a family history of TS is of prime importance.</p>

Changes of Intercellular Adhesion Molecule-1 in Pathogenesis of Children with Mycoplasm Pneumoniae Pneumonia / 实用儿科临床杂志

Objective To determine the levels of soluble intercellular adhesion molecule-1(SICAM-1) in serum and induced sputum in children with mycoplasma pneumoniae pneumonia(MPP),and to investigate the role of SICAM-1 in pathogenesis of MPP.Methods The levels of SICAM-1 in serum and induced sputum and sputum cell count were measured by enzyme linked immunosorbent assay(ELISA) kit in 44/34 children with MPP in acute episode period,36/28 children in remission episode period and 38/30 healthy children.Results The levels of serum SICAM-1,sputum SICAM-1 and percent of neutrophil(N),lymphocyte(L),eosinophile(EO),mast cell(Ma) were significantly higher in acute episode period in MPP than those in remission episode period and control group,respectively((all P0.05);)the indexs in remission period and in controls showed no marked difference.The le-(vels of) serum and sputum(SICAM-1) in children with asthma attack in acute and remission episode periods in MPP increased significantly compared with those in children without asthma in both periods(P

Evaluation of Heart Function and Observation of Clinical Prognosis of Dilated Cardiomyopathy in Children Treated with Different Immunotherapies / 实用儿科临床杂志

Objective To compare the heart function and observe the clinical prognosis of dilated cardiomyopathy(DCM) in children treated with combination of prednisone and azathioprine and high dose intravenous immunoglobulin(IVIG).Methods From Jan.1998 to May 2004,20 children who met the diagnostic criteria of DCM were divided into 2 therapeutic groups(groupⅠ,groupⅡ) according to the time of hospitalization.On the basis of traditional congestive heart failure(CHF) therapy,the children in groupⅠwere treated with immunosuppressive therapy(prednisone plus azathioprine) and the children in groupⅡ were treated with high dose IVIG.The course of treatment was 6 months for all children.Heart functions in all children were evaluated and echocardiographic parameters including left auricular diameter(LA),left ventricular end diastolic diameter(LV),left ventricular ejection fraction(LVEF) and cardiac index(CI) were measured before and after therapy,respectively.All children were followed up for 1 year to observe survival rate(%).The findings were analyzed by t test and ?~2 test.Results The percentage of heart function increased from Ⅲ-Ⅳ toⅠ-Ⅱin groupⅠ,which was lower than that in groupⅡ(P

Inhibitory action of propyl gallate on the activation of SAPK/JNK and p38MAPK induced by cerebral ischemia-reperfusion in rats / 药学学报

<p><b>AIM</b>To explore the protective effect of propyl gallate against neuronal injury in the boundary zone of the infarction area in the rat cerebral ischemia-reperfusion model and its possible mechanism.</p><p><b>METHODS</b>Transient focal ischemia induced by middle cerebral artery occlusion in the rats was established by ligation of the left internal carotid artery for 2 h. Rats were treated by propyl gallate with different doses (23.5, 47 and 94 micromol x kg(-1)) for three days before operation. Coronal brain sections were collected after 1 , 2, 4, 6, 12 and 24 h of reperfusion, neuronal injury in the boundary zone of the infarction area was evaluated by TUNEL and Nissl staining. The expression of activated Caspase-3, total SAPK/JNK, p38MAPK and their phosphorylation (Thr183/Tyr185, Thr180/Tyr182) was investigated by immunohistochemistry and Western blotting with corresponding antibodies.</p><p><b>RESULTS</b>Although SAPK/JNK immunoreactivity did not increase at each time point in the boundary zone of the infarction area after reperfusion, p-SAPK/JNK immunoreactivity increased significantly at 1 h and then decreased gradually, and p38MAPK immunoreactivity was enhanced at each time point, peaked at 6 h. Expression of p-p38MAPK peaked at 6 h. Activated Caspase-3 immunoreactivity appeared at 6 h in the boundary zone of the infarction area and peaked at 12 h. TUNEL positive neurons were observed at 12 h and became more abundant at 24 h. The number of Nissl positive neurons decreased gradually and apoptosis ratio of neurons peaked at 24 h. Propyl gallate reduced the immunoreactivity of SAPK/JNK, p-SAPK/JNK, p38MAPK and p-p38MAPK markedly at 1 and 6 h. Propyl gallate with doses of 47 and 94 micromol x kg(-1) were more effective.</p><p><b>CONCLUSION</b>Inhibition on the activation of SAPK/JNK and p38MAPK is the possible protective mechanism of propyl gallate against neuronal injury induced by cerebral ischemia-reperfusion.</p>

Relationship of variation 3057 G-->A of exon 20 of leptin receptor gene to lipid metabolism and fat distribution of children with obesity / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the relationship of the variation of exon 20 of leptin receptor (LEPR) gene to the lipid metabolism and fat distribution of the children with obesity.</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism(RFLP) and polyacrylamide gel electrophoresis were used to analyze the variation of exon 20 of the LEPR gene of the obesity group(72 obesity children) and the control group(60 healthy children). At the same time, all childrens' serum triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), height and weight were measured, and their body mass index(BMI) and fat percent(%fat) were calculated.</p><p><b>RESULTS</b>Three genotypes of exon 20 of LEPR gene were detected in this study. Compared with the control, the frequency of gene variation at 3057 nucleotide G-->A transversion was higher(P<0.05). The concentration of serum TG and the BMI and %fat of the A/A genotype obesity children were higher than those of the G/G genotype ones(P<0.01) but the level of serum HDL of the A/A children were lower than that of the G/G children (P<0.01). As to the G/A genotype children, only their serum TG level was higher than that of the G/G genotype ones(P<0.05).</p><p><b>CONCLUSION</b>The above findings indicated there were polymorphisms in the children with obesity, and those polymorphisms might remarkably affect their lipid metabolism and fat distribution.</p>

Application of Cook MOB-15 system in guiding wire insertion during endoscopic retrograde cholangiopancreatography / 第二军医大学学报

Objective:To evaluate the value of Cook MOB-15 system in guiding wire insertion during endoscopic retrograde cholangiopancreatography (ERCP). Methods: The clinical data of 51 patients who received Cook MOB-15 system-guided wire insertion during ERCP between Jan. 2005 to Dec. 2007 were retrospectively analyzed. Forty patients who received conventional ERCP catheter for malignant jaundice between Jan. 2002 and Dec. 2004 were taken as control. The successful insertion rates were compared between the 2 groups. Results: The successful insertion rate was 90.2% (46/51) in the Cook MOB-15 system group and 72.5% (29/40) in the conventional group; there was significant difference between the 2 groups (P