Chronic phosphoproteomic in temporal lobe epilepsy mouse models induced by kainic acid / 北京大学学报(医学版)

OBJECTIVE@#To investigate functions of proteins and signaling pathways involved in epileptogenesis during the chronic stage of temporal lobe epilepsy in mouse models.@*METHODS@#Kainic acid-induced temporal lobe epilepsy models were conducted, when reaching stage 4 using racine scale, the mice of experimental group were supposed to be successfully established. Pentobarbital sodium was injected to stop epileptic seizure in case of death. Twenty-eight days after the kainic acid injection, when the experimental group generally turned into chronic spontaneous seizures, mice hippocampal tissues were extracted from the control and the experimental groups respectively for phosphoproteomic. Enriched phosphorylated proteins were detected using mass spectrometry, only the proteins whose density was greater than 106 were analyzed by matching the Gene Ontology (GO) database, Kyoto Encyclopedia of Genes and Genomes (KEGG) database and STRING database to detect proteins involved in epileptogenesis in protein functions, signaling pathways and protein-protein interaction respectively. After that, literatures were reviewed about the key proteins.@*RESULTS@#(1) Total of 12 697 phosphorylation sites of enriched proteins were detected by mass spectrometry, and there were 159 sites whose phosphorylation levels were significantly different from the control (P<0.001). (2) GO database showed that 35.7% of the 159 sites were about "catalytic activity", 39.5% were about "binding" and 20.8% were about "cell communication", and the 159 proteins also participated in many biological processes, such as "primary metabolic process" "response to stimulus" "developmental process" "localization" and "phosphate-containing compound metabolic process". (3) KEGG database showed that the 159 protein sites mainly involved in 10 signaling pathways: glutamatergic synapse, Ras signaling pathway, African trypanosomiasis, Cocaine addiction, Circadian entrainment, Amyotrophic lateral sclerosis (ALS), Long-term potentiation, Endocytosis, Gap junction, Nicotine addiction. (4) STRING database showed that the protein-protein interaction network formed by the 159 proteins was focused on Grin1/Dlg3, Arhgef 2/Arhgap33/Tiam1 and Sptnb1/3/4/Add3/Ank2 protein group respectively. (5) Phosphorylation levels of Grin1, Arhgef 2, Arhgap33, Tiam1, Sptbn1/2/4 and Ank2 in experimental group were significantly higher than in the control (P<0.001).@*CONCLUSION@#Phosphoproteomic illustrated integral distribution of phosphorylated proteins at the chronic stage of temporal lobe epilepsy in the mouse model. Literatures showed that most key proteins were closely related to epileptogenesis, suggesting that some proteins or signaling pathways may play a role in epileptogenesis, such as dopamine and Kir3.1.

Immune Tolerance Therapy: A New Method for Treatment of Traumatic Brain Injury / 中华医学杂志(英文版)

Objective@#Due to the special anatomical structure and pathophysiological mechanism of the central nervous system (CNS), there is a big difference between the repair of brain injury and other systems of the body. More and more evidence shows that targetedly reducing the autoimmune response of brain tissue without affecting the immune function in other parts of the body will be the best optimized treatment for brain injury.@*Data Sources@#This review was based on data in articles published in PubMed up to June 5, 2017, with the following keywords: "immune tolerance", "traumatic brain injury", and "central nervous system".@*Study Selection@#Original articles and critical reviews on immune tolerance and brain damage were selected for this review. References of the retrieved articles were also screened to search for potentially relevant papers.@*Results@#The CNS is isolated from the immune system through the blood-brain barrier. After brain injury, brain antigens are released into the systemic circulation to induce damaging immune responses. Immune tolerance can effectively reduce the brain edema and neurological inflammatory response after brain injury, which is beneficial to the recovery of neurological function. The clinical application prospect and theoretical research value of the treatment of immune tolerance on traumatic brain injury (TBI) is worth attention.@*Conclusions@#The establishment of immune tolerance mechanism has a high clinical value in the treatment of TBI. It opens up new opportunities for the treatment of brain damage.

Study on the association of oral contraceptives, angiotensinogen gene polymorphisms and the risk of stroke in women / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the associations of oral contraceptives (OC) exposure, angiotensinogen (AGT) gene polymorphism and joint effects on the risk of stroke in Chinese women.</p><p><b>METHODS</b>On the basis of a prospective female cohort of contraceptive use, the first-ever-developed (FED) stroke cases, as well as, two sets of age-(± 3 years) and region-matched controls (including neighborhoods and hospitalized patients) were recruited. Between 1 July 2000 and 30 June 2009, a total of 453 FED stroke cases and 919 controls were recruited. Genotyping for polymorphisms of AGT gene was detected by Taqman method.</p><p><b>RESULTS</b>(1) The risk of stroke gradually increased with the cumulative time of OC use in women (P < 0.0001). Compared with the non-users, the risk of hemorrhagic stroke slightly increased among those with OC use (OR = 1.83, 95%CI: 1.25 - 2.66). (2) Women with AG/GG genotypes of A-6G locus or CA/AA genotypes of C11535A locus indicated that there was a slightly reduced risk of stroke (OR = 0.78, 95%CI: 0.61 - 0.99; OR = 0.73, 95%CI: 0.56 - 0.95). (3) Women with AA genotypes of A-20C locus and AG/GG genotypes of A-6G, when incorporated with CA/AA genotypes of C11535A locus with OC, it could increase the risk of hemorrhagic stroke (OR = 1.99, 95%CI: 1.34 - 2.97; OR = 1.84, 95%CI: 1.15 - 2.94; OR = 1.73, 95%CI: 1.06 - 2.85).</p><p><b>CONCLUSION</b>The AGT gene polymorphisms showed that they did have an impact on the risk of stroke. And the joint effect between women using OC and AGT gene polymorphisms could slightly increase the risk of stroke.</p>

Study on the association of oral contraceptives, angiotensin-converting enzyme gene polymorphisms and risk of stroke in women / 中华流行病学杂志

Objective To evaluate the associations of oral contraceptives (OC) exposure,angiotensin-converting enzyme(ACE) gene polymorphism and their joint actions with the risk of stroke in Chinese women.Methods A case-control study,based on a set cohort,was carried out.Incident cases of stroke identified between July 1 1997 and June 30 2009 were enrolled.One hospital control and healthy community control were matched on region and age ( ± 3 years).A total of 453women with stroke and 919 controls were recruited.I/D genepolymorphism was detected by polymerase chain reaction (PCR) and amplification fragment length polymorphism (AFLP),A-240T polymorphism were detected by TagMan.Results ( 1 ) The risk of stroke gradually increased with the cumulative time of OC being used in women (P＜0.0001).Compared with non-users,the risk of stroke significantly increased among those with cumulative time of using OC longer than 20 years (adjusted OR was 2.07,with 95％ CI as 1.30-3.29).(2) ID/DD genotype of I/D locus indicated significantly an increased risk of hemorrhagic stroke (adjusted OR,2.37; 95％CI,1.46-3.84).(3)Women with ID/DD genotype of I/D locus or with TA/TT genotype of A-240T locus and using OC could significantly increase the risk of hemorrhagic stroke (adjusted OR was 4.59; with 95％ CI as 2.21-9.51 and OR was 2.50; with 95％CI as 1.42-4.38).(4) Data from multivariate analyses showed that both OC and ID/DD genotypes were important risk factors for hemorrhagic stroke.Conclusion ID/DD and TA/TT genotypes of ACE gene,OC and their joint action might increase the risk of stroke,especially on hemorrhagic stroke in Chinese women.

Effects of male reproductive health information education communication on mastering STDs knowledge among young couples / 中华男科学杂志

<p><b>OBJECTIVES</b>To increase the knowledge of STDs control and prevention among young couples by intervention, and to improve their reproductive health.</p><p><b>METHODS</b>The intervention plan was made and carried out on the basis of the information from baseline interview and Focus Group Discussions. The activities of the intervention included lectures given by experts, counseling service, delivering knowledge foldouts and knowledge competition. The final survey was conducted. The data of baseline and final survey were analyzed with SAS software.</p><p><b>RESULTS</b>Before intervention, young couples knowledge of STDs was similar between the experimental and the control group. After intervention, proportion of knowing numbers of STDs kinds in experiment group significantly was higher than that in control group(P < 0.01); The proportion of knowing harm of STDs and knowing to use consom to prevent STDs couples were significantly higher in experiment group than that in control group(P < 0.01).</p><p><b>CONCLUSIONS</b>The intervention activities including lectures and counseling services were positive and great sociological affects on family planning and reproductive health improvement for young couples which has one child.</p>