Association of MDR1 gene polymorphisms with refractory epilepsy in children / 中华医学遗传学杂志

Objective@#To assess the association of single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) with refractory epilepsy in children.@*Methods@#Peripheral blood samples were collected from 200 children with epilepsy and 100 healthy controls. Genomic DNA was extracted and subjected to PCR amplification, agarose gel electrophoresis and target site sequencing. Genotypes of rs1922242, rs2235048, rs10808072, rs868755 and rs1202184 loci of the MDR1 gene were analyzed.@*Results@#No significant difference was found in genotypic distribution and allelic frequencies of the rs1922242, rs2235048, rs10808072 and rs868755 loci between the drug-resistant and drug-sensitive groups. For the rs1202184 locus, a significant difference in genotypic distribution was found (P = 0.008). No significant difference was found in the frequencies of various haplotypes between the two groups.@*Conclusion@#Genotypes of the rs1202184 locus of the MDR1 gene are associated with refractory epilepsy in children, for which the AA genotype plays a dominant role.

Association of MDR1 gene polymorphisms with refractory epilepsy in children / 中华医学遗传学杂志

OBJECTIVE@#To assess the association of single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) with refractory epilepsy in children.@*METHODS@#Peripheral blood samples were collected from 200 children with epilepsy and 100 healthy controls. Genomic DNA was extracted and subjected to PCR amplification, agarose gel electrophoresis and target site sequencing. Genotypes of rs1922242, rs2235048, rs10808072, rs868755 and rs1202184 loci of the MDR1 gene were analyzed.@*RESULTS@#No significant difference was found in genotypic distribution and allelic frequencies of the rs1922242, rs2235048, rs10808072 and rs868755 loci between the drug-resistant and drug-sensitive groups. For the rs1202184 locus, a significant difference in genotypic distribution was found (P=0.008). No significant difference was found in the frequencies of various haplotypes between the two groups.@*CONCLUSION@#Genotypes of the rs1202184 locus of the MDR1 gene are associated with refractory epilepsy in children, for which the AA genotype plays a dominant role.

Clinical, imaging features and follow-up study of schizencephaly in 35 children / 中华实用儿科临床杂志

Objective To summarize the correlation between clinical manifestations and imaging characteristics of schizencephaly in order to provide a basis for the diagnosis and prognosis.Methods Thirty-five outpatients with schizencephaly diagnosed at Department of Pediatric Neurology of Henan Provincial People's Hospital from January 2009 to May 2015 were retrospectively selected,and they were divided into different groups (patients with unilateral lesions or bilateral lesions) according to their cranial magnetic resonance imaging (MRI) features.The clinical manifestations were compared between different groups.Results Of 35 patients,19 (54.3％) patients were male and 16 (45.7％) patients were female.Twenty-four patients were found with unilateral lesions (68.6％),including 16 cases (66.7％) with hemiparesis and 8 cases(33.3％) with no motor impairment.Mental retardation was observed in 8 patients (33.3％) and 6 patients (25.0％) showed speech impairment.Eleven patients were found the bilateral lesions (31.4％),including 5 patients (45.4％) with tetraparesis,4 patients (36.4％) with hemiparesis,and 2 paticnts (18.2％) with no motor impairment.Mental retardation was observed in 9 patients (81.8％) and 9 patients (81.8％) showed speech impairment.There were significant differences in motor impairment,mental retardation and speech impairment between the unilateral lesion group and bilateral lesion group (Z =-2.40,P =0.002;x2 =7.09,P =0.012;x2 =9.94;P =0.003).Epileptic seizure occurred in 18 patients (51.4％).Binary Logistic regression analysis indicated that cortical dysplasia beyond the cleft and open-lip lesions were the major risk factors for seizures (OR =4.44,2.73;P =0.005,0.029).Imaging characteristics:there were closed-lip lesions in 10 patients (28.6％),open-lip lesions in 21 patients (60.0％) and open/closed-lip lesions in 4 patients (11.4％).Anatomic localization of all clefts was found in the frontal lobes in 19 patients (54.3％),in frontoparietal lobes in 11 patients (31.4％),in parietal lobes in 2 patients (5.7％),and in occipital lobes in 3 patients (8.6％).After 1-6-year follow-up,12 patients treated with antiepileptic drug were seizure-free (all with unilateral lesions),and 6 patients had refractory epilepsy (3 patients with bilateral lesions).Conclusions Schizencephaly is a rare structural disorder of cerebral cortical development.Those with bilateral lesions are usually manifested with severe motor,speech impairment and mental retardation and their prognosis is poor.Schizencephaly patients complicated with cortical dysplasia beyond the cleft or open-lip lesions are more easily attacked by seizures.MRI plays an important role in the diagnosis and prognosis judgment of schizencephaly.

Early apoptosis leads to decrease of B cells in MRL/lpr mice / 中国免疫学杂志

Objective:To explore the change of B cell numbers in active MRL/lpr lupus mice , and their regulation mechanisms.Methods:B cell cycle and the percent of B cells in spleen lymphocytes of active MRL /lpr lupus mice and normal C 57/B6 mice were analyzed by using flow cytometry .The apoptotic B cells and their subclass were analyzed by Annexin V and PI staining.Further more ,B cells were purified by magnetic sorting , and real-time quantitative PCR was carried out to detect apoptosis-related gene.Results:Compared with the C57/B6 mice,the percent of B cells in active MRL/lpr lupus mice were significantly reduced (P<0.01),while the percent of apoptotic cells were significantly increased (P<0.01).The percent of early apoptotic B cells were sig-nificantly increased ( P <0.01 ) which including the immature and mature B cells , while the late apoptotic B cells were unchanged.Further more,we found that the anti-apoptotic protein BIRC3 was significantly reduced in active lupus B cells (P<0.01), while the pro-apoptotic protein BCL2L1 and BBC3(PUMA) were significantly increased(P<0.01).Conclusion: B cells in active lupus mice were significantly reduced while early apoptotic B cells were increased , which may be attributed to the changed balance between the anti-apoptotic and pro-apoptotic proteins , suggesting the reduction of B cells in SLE patients may be related to their increased early apoptosis .

JMJD3 participates in activation and apoptosis of IFN-αand TLR7-induced B cells / 中国免疫学杂志

Objective:To explore the effect of histone demethylase JMJD3 on B cell activation and apoptosis.Methods:B cells were sorted and purified from the peripheral blood of healthy people and SLE patients by using magnetic bead.After B cells were treated with IFN-αor R848 or IFN-α+R848,the percentages of CD86+B cells,CD69+B cells,CD86+Annexin V+B cells and CD69+Annexin V+B cells were detected by flow cytometry.The expression of JMJD3 was detected by Real Time PCR and Western blot.Results:The purity of sorted B cells was up to 95%.IFN-αenhanced both the activation and apoptosis and the JMJD3 expression of TLR7-activated B cells.The expression of JMJD3 was dependent on MAPK signal pathway,but not the NF-κB signaling pathway.Moreover,JMJD3 was highly expressed in B cells of peripheral blood from SLE patients compared to those from healthy people.Furthermore,JMJD3 inhibitors could inhibit the activation and apoptosis of IFN-αand R848 activated B cells.Conclusion:JMJD3 participated in the activation and apoptosis of IFN-αand TLR7-induced B cells, suggesting JMJD3 inhibitors may possess therapeutic effect for alleviating symptom of SLE.