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Objective:To investigate the influences of SCN3A gene polymorphism(c.905A>G/p.N302S and c. 1441C>T/p.L481L) on the efficacy of valproic acid sodium in the treatment of Zhuangzu epilepsies.Methods:Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)technique and the way of direct sequence, the SCN3A gene c. 905A>G/p.N302S and c. 1441C>T/p.L481L genotypes in peripheral blood were detected in 244 epileptic patients (85 cases in effective group and 139 cases of ineffective group) in the standardized treatment of valproic acid sodium.The blood concentration of valproic acid sodium was detected by LC-MS.Evaluating the correlation between the genotype and alleles of two groups of patients and the efficacy of valproic acid sodium and analyzing the difference of valproic acid sodium's blood concentration between different genotypes.The linkage disequilibrium of c. 905A>G/p.N302S and c. 1441C>T/p.L481L were analyzed by software SHEsis.Results:The allele and genotype distribution in c. 905A>G/p.N302S loci between effective group(A, G allele: 50.6%, 49.4%, AA, AG, GG genotype: 27.1%, 47.1%, 25.8%) and ineffective group(A, G allele: 37.4%, 62.6%, AA, AG, GG genotype: 16.6%, 41.7%, 41.7%) had statistically significant difference(χ 2=7.501, P=0.006; χ 2=7.907, P=0.019). There was no significant difference in allele and genotype distribution of c. 1441C>T/p.L481L loci between effective group(C, T allele: 47.1%, 52.9%, CC, CT, TT genotype: 23.5%, 47.1%, 29.4%) and ineffective group(C, T allele: 38.8%, 61.2%, CC, CT, TT genotype: 18.7%, 40.3%, 41.0%)(χ 2=2.920, P=0.088; χ 2=3.099, P=0.212). Compared with the AA + AG genotype, the GG genotype at c. 905A>G/p.N302S locus significantly reduced the efficacy of valproic acid sodium ( OR=2.051, 95% CI=1.136-3.703). Compared with genotypes AA+ AG, there were no significant differences in blood concentration of genotype GG of c. 905A>G/p.N302S ( t=3.256, P=0.137). Compared with genotypes CC+ CT, there were no significant differences in blood concentration of genotype TT of c. 1441C>T/p.L481L( t=4.628, P=0.082). c.905A>G/p.N302S and c. 1441C>T/p.L481L were without linkage disequilibrium. Conclusion:These results suggest that the single nucleotide polymorphisms of c. 905A>G/p.N302S in SCN3A genes may play a role in the resistivity of valproic acid sodium in Zhuangzu epilepsies.
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OBJECTIVE@#To assess the association of polymorphisms of rs3819024 and rs8193037 loci in the promoter region of IL-17A gene with the risk of ischemic stroke (IS) among ethnic Han Chinese from Guangxi.@*METHODS@#The polymorphisms of rs3819024 and rs8193037 loci were detected by a SNaPshot assay and DNA sequencing among 392 IS patients and 443 healthy controls with matched age and gender.@*RESULTS@#The genotypes, dominant model, recessive model, and alleles of rs3819024 polymorphisms showed no significant difference between the two groups, with the P values calculated as 0.150, 0.227, 0.125, 0.594 and 0.202, respectively, and OR (95% CI) as 1.27(0.92-1.74), 1.28(0.86-1.91), 1.27(0.94-1.72), 1.10(0.78-1.54), and 1.13(0.94-1.38), respectively. The genotypes, dominant model, recessive model, and alleles of rs8193037 polymorphisms also showed no significant difference between the two groups, with the P values calculated as 0.722, 0.352, 0.863, 0.345 and 0.969, respectively, and OR (95% CI) as 0.94(0.65-1.35), 2.25(0.41-12.35), 0.97(0.68-1.38), 2.27(0.41-12.48), and 1.01(0.72-1.40), respectively.@*CONCLUSION@#Polymorphisms of the rs3819024 and rs8193037 loci of the IL-17A gene are not associated with the susceptibility to IS among ethnic Han Chinese from Guangxi.
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Humans , Alleles , Asian People , Brain Ischemia , Genetics , Case-Control Studies , China , Gene Frequency , Genetic Predisposition to Disease , Genotype , Interleukin-17 , Genetics , Polymorphism, Single Nucleotide , Stroke , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the association of SNP of CD40 gene and its serum levels with ischemic stroke (IS).</p><p><b>METHODS</b>A total of 202 IS patients from a hospital of Baise city were enrolled in case group from May 2013 to November 2014. At the same time, 109 healthy people who had physical check-ups in the outpatient department at the same hospital were enrolled in the control group. All participants were from Guangxi Zhuang Autonomous Region and unrelated to each other. 3 ml venous blood were collected on the premise of informed consent. The single nucleotide polymorphisms of CD40 gene rs1883832 C/T, rs13040307 C/T, rs752118 C/T and rs3765459 G/A were analyzed using a Snapshot SNP genotyping assays, and the serum levels of CD40 were tested by ELISA. t-test was used to compare the serum levels of CD40 between the case and control group, and the genotypes at different locuses in case group; χ(2) test was used to compare the distribution differences of the CD40 gene locuses in different genotypes and allele between the case group and the control group; alleles was established as independent variables, the occurrence of the IS as dependent variable, and expressed relative risk with OR (95%CI) value.</p><p><b>RESULTS</b>In the case group, the frequency of CC, CT and TT genotypes in CD40 gene rs1883832 C/T were 21.78% (44/202), 49.51% (100/202) and 28.71% (58/202), respectively, and 33.17% (66/199), 48.74% (97/199), 18.09% (36/199) in the control group, respectively, the differences between the two groups was significant (χ(2)=9.57, P=0.008). The CD40 serum levels were (62.7 ± 24.5) pg/ml in the case group, which was higher than that in the control group (45.3 ± 17.2) pg/ml (t=8.97, P<0.001). The serum levels of TT and CT genotypes in CD40 gene were (65.9 ± 26.3) and (64.3 ± 25.9) pg/ml, respectively, and the differences were significant when comparing with CC genotype (t equaled 5.34 and 5.03, respectively, P<0.001). The risk of developing IS was 1.56 times higher in 1883832 T allele carriers than that in rs1883832 C allele carriers (OR=1.56, 95% CI: 1.18-2.06); Combined genotype analysis displayed that CD40 gene rs1883832 C/T, rs13040307 C/T, rs752118 C/T and rs3765459 G/A polymorphisms showed strong linkage disequilibrium, the case group TCCA haplotype was tested to be associated with a significantly increased risk of IS as compared with that in the control group(OR=2.49; 95%CI: 1.13-5.48).</p><p><b>CONCLUSION</b>CD40 gene rs1883832 C/T polymorphism and its TCCA haplotype were possibly associated with ischemic stroke, and the susceptibility gene for ischemic stroke may be rs1883832 T allele.</p>
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Humans , Alleles , CD40 Antigens , Blood , Genetics , Case-Control Studies , Cell Differentiation , China , Gene Frequency , Genetic Predisposition to Disease , Genotype , Haplotypes , Polymorphism, Single Nucleotide , Stroke , Blood , GeneticsABSTRACT
Objective To investigate the frequency of lesions detection in patients with cerebral infarction (CI) with SPECT/CT. To investigate fluctuation of regional cerebral blood flow (rCBF) and its relationship with clinical symptoms. Methods Sixty-seven CI patients without cerebellar lesion were randomly selected. The rCBF in the regions of interest (ROI) was examined by SPECT/CT, which was collected from the frontal lobe, temporal lobe, parietal lobe, occipital lobe, thalamus, basal ganglia and cerebellum. The rCBF index was calculated. The association between fluctuation of rCBF index and clinical symptoms of patients was explored. Results There were 251 positive regions in all viewing regions , the total positive rate was 31.2%. The left side was 38.1%, while the right side was 24.4% (χ2=17.522,P 0.05). However, the average rCBF on the left parietal lobe was lower (P 0.05). rCBF≥0.7 is a clinical sign of abnormal ROI. Conclusion 30% of ROI of CI patients have lesions and the positive rate of the left side was higher. The biological rCBF values of all lobes were different. Therefore, rCBF index could be used to reflect whether the ROI is normal. rCBF≥0.7 could be used as a sign to quantitatively assess abnormal ROI in clinical practice.
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Objective To study the relationship between ischemic stroke and gene polymorphism of an-giotensin-converting enzyme (ACE), apolipoprotein E (APOE) and methylene tetrahydrofolate reductase (MTHFR) among the population of Zhuang nationality in western Gui. Methods We directly sequenced ACE, APOE and MTHFR genes in 149 cases of ischemic stroke and 109 cases of normal people in western Gui. χ2 test was used to measure the relationship between gene polymorphism and ischemic stroke. Hardy-Weinberg genetic equilibrium test was used to evaluate the reliability of these data. Results In the ischemic stroke group, 62 cases, 22 cases and 65 cases carried II genetype, DD genetype and ID genetype in ACE. χ2 test showed no relationship between ACE gene polymorphism and ischemic stroke. In analysis of the polymorpism of APOE in the ischemic stroke and control group, no relationship between APOE gene polymorphism and ischemic stroke was found by χ2 test. MTFHR gene polymorphism was significantly related with ischemic stroke by χ2 test (P = 0.019). Conclusion Polymorphism of gene MTFHR but neither ACE nor APOE is significantly associated with ischemic stroke.
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Objective To investigate the time course of nuclear factor-κB(NF-κB) and the effects of pyrrolidine dithiocarbamate (PDTC) on the expressions of NF-κB,tumor necrosis factor-α (TNF-α) and interleukin1β(IL-1β) in hippocampus after seizures.Methods Epilepsy were induced by [PTZ] through Intraperitoneal injection.Western blotting was used to detect NF-κB p65 expression in nucleus at various experiment groups in different time points( 14d,21 d,28d,35d).Moreover,mRNA and protein expressions of TNF-α and IL-1β in different experiment groups in different time points by Real-time quantitative PCR and ELISA analysis.Results The expression of NF-κB p65 began to increase in the nuclear fraction in 14d,kept rising in 28d and returned to 14d level in 35d after epilepsy seizures,At 14d,21d,28d and 35d,the expressions of NF-κB in PDTC groups ( (0.54 ±0.07),(0.65 ± 0.08 ),(0.78 ± 0.10),(0.78 ± 0.10) ) was significantly lower than those in PTZ groups ((1.20 ±0.11),(1.42 ±0.14),(1.88 ±0.16),(1.25 ±0.10)) (P＜0.01).After epilepsy seizures,the expression of TNF-α 、IL-1β mRNA was increased in PTZ groups( ( 1.34 ±0.13,0.81 ± O.17 ),( 1.64 ±0.17,1.56±0.20),(2.03 ±0.16,1.65 ±0.18),(1.40 ±0.10,1.30 ±0.13) ) than those in NS groups(P＜0.01 ) ;and compared with PTZ groups PDTC significantly decrease the mRNA expressions of TNF-α and IL-1 β in PDTC groups( (0.96 ±0.1,0.57 ±0.07),(1.36 ±0.15,1.09 ±0.18),(1.47 ±0.14,1.25 ±0.16),(1.12 ±0.12,O.85 ± 0.12) ) (P ＜ 0.05 ).The expressions of TN F-α,IL-1β protein were similar in hippocampal by ELISA.Conclusion Seizures induces NF-κB nucleus translocation and promotes the expressions of TNF-ot and IL-1 β in hippocampus and pyrrolidine dithiocarbamate suppresses NF-κB associated inflammatory pathway in epileptic rat hippocampus.
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AIM: To observe clinical efficacy of Tanreqing Injection (Radix Scutellariae, Bear gall powder, Ram's horn, Flos lonicerae japonicae and Fructus forsythiae) in treatment of patients with acute attack of bronchial asthma. METHODS: One hundred and seven patients with an acute asthma were randomly assigned into two groups: a treatment group (n=52, treated by Tanreqing Injection for 10 d in addition to the routine medications) and a control group (n=55, treated by routine medications). The serum levels of ET and TNF-α were determined by radioimmunoassay before and after treatment, respectively. RESULTS: Before treatment, there were no significant differences in the content of serum ET and TNF-α between the treatment group and the control group. However, after 10 d of treatment, the levels of ET and TNF-α inthe treatment group were significantly lower than those of the control group (P<0.01), and clinical efficacy of the treatment group was superior to the control group. CONCLUSION: Inhibitionof ET and TNF-α secretion and intervention inflammatory response might be one of mechanisms of Tanreqing Injection in treatment for acute asthma.
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Objective To study the effects of enriched rehabilitative training on the expression of microtu-bule associated protein 2 (MAP-2) and synaptophysin (SYN), and to explore its relationship with brain plasticity. Methods Seventy-seven male Wistar rats weighing 160 to 200 g were randomly divided into an ischemia + enriched rehabilitation group (IE, n=36), an ischemia + standard rehabilitation group(IS, n=8), a sham ischemia + en-riched rehabilitation group (SE, n=21) and a sham ischemia + standard rehabilitation group (SS, n=12). Rats in the ischemia groups had their middle cerebral artery sutured for two hours before reperfusion, while those in the sham groups had a similar operation without occlusion. The enriched groups were given enriched rehabilitative train-ing, while the standard groups were left without any training. Behavioral tests, including the acrobatic performance, were administered once daily 2 days after operation, and SP staining of MAP2 and SYN were used to observe the func-tional recovery and brain plasticity changes among the groups at 1,7, 14, 21 and 28 days after the operations. Re-sults Acrobatic performance times reduced gradually. Bederson scores were significantly better in the IE than in the IS group by the 28th day after the operation). There was no significant difference between IE and IS groups in a foot fault test). The expression of MAP-2 and SYN around the infarct and in the hippocampus decreased significantly at first), then recovered gradually. The expression of MAP-2 and SYN in the IE group was significantly higher than that in the IS group at various time points of observation). Conclusion Enriched rehabilitative training can improve functional recovery and the expression of MAP-2 and SYN after brain ischemia, and the functional enhancement may attribute to the brain plasticity.
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Objective To explore the clinical significance of cerebrospinal fluid neuropeptide Y in epileptic patients with intelligence disturbance.Methods The Full Intelligence Quotient (FIQ) of 78 cases of epileptic patients were assessed by WAIS-RC.The subjects were divided into intelligence disturbance group and non-intelligence disturbance group.Their cerebrospinal fluid neuropeptide Y Was tested by using radio immunoassay.Results The content of neuropeptide Y in intelligence disturbance group Was obviously higher than that in non-intelligence disturbance group (P<0.01).Conclusion Intelligence disturbance in epileptic patients is related to the increased Neuropeptide Y.Neuropeptide Y may reflect the intelligence condition in epileptic patients.
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@#ObjectiveTo study the effect of enriched rehabilitative training on the functional recovery and neuronal dentritic growth following cerebral ischemia/reperfusion.Methods32 male Wistar rats,weighting 180～200 g,were randomly divided into a ischemic group(n=16) and a sham-operation group(n=16) after beforehand trainings.Rats were subjected to 2 h of right middle cerebral artery occlusion before reperfusion.After surgery,the ischemic group were randomly divided into a ischemia + enrichment(IE) group and a ischemia + standard housing(IS) group;the sham-operation group were randomly divided into a sham + enrichment(SE) group and a sham + standard housing(SS) group.After 24 h reperfusion,IE and SE groups were housed in enriched cages,and given enriched rehabilitative training according to the scheme.At the same time,IS and SS groups were housed in standard cages without any training.The functions of 4 groups were evaluated at 24 h,1 week,2 weeks,3 weeks and 4 week after operation.Dentritic growth of layer V pyramidal cells of the undamaged forelimb motor cortex was examined using Golgi-Cox procedure.ResultsIE group showed better function than IS group in all behavioral test.There was no significant difference in limb-placement test at 3 weeks(P>0.05) and in footfault test at 4 weeks(P>0.05) after operation between IE and SE group.The mean of basilar dentrite branching points in IE group was significantly greater than that of other groups(P<0.01).ConclusionEnriched rehabilitative training can promote functional recovery and enhance neural plasticity after cerebral ischemia/ reperfusion in rats.
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@#ObjectiveTo investigate the effects of Angelica sinensis on the expression of vascular endothelial growth factor (VEGF) Flt-1, Flk-1 mRNA after the brain ischemia-reperfusion injury in rats.MethodsWistar rats were randomly divided into the group A, group B and normal control group. The group A underwent middle cerebral artery occlusion (MCAO) for 2h by suture, group B underwent MCAO for 2h meanwhile received treatment with Angelica sinensis (5 g/kg). Immunohistochemistry and quantitative reverse transcription and polymerase chain reaction (RT-PCR) technique were used to examine the gene expression of VEGF.ResultsThe result of immunohistry revealed that VEGF in the group A and group B reached its peak at 24 h after reperfusion then declined gradually. The result of RT-PCR manifested that the gene expression of VEGF in the group A increased from 3 h after reperfusion and reached its peak at 6 h; in the group B reached its peak on the 3rd day. The expression of VEGF in the group B was significantly increased than group A at the same time point.ConclusionAngelica sinensis can enhance the expression of Flt-1, Flk-1 after transient interruption of cerebral blood flow in rats.
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Objective To study the relationship between polymorphisms of E-selectin gene and ischemic stroke (IS) in Zhuang nationality of Guangxi province. Methods The G98T polymorphism in the exon 2 and the S128R polymorphism in the exon 4 of E-selectin gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing among 205 patients with IS of Zhuang nationality in Guangxi and 210 healthy controls. The serum level of E-selectin was determined by enzyme-linked immunosorbent assay (ELISA). Results IS group showed significantly higher serum levels of E-selectin than control group (P0.05). Conclusion E-selectin S128R polymorphism was associated with IS, and R allele may be a genetic risk factor of IS among Guangxi Zhuang natioalities, in whom the E-selectin SR genotype carriers maybe increase the risk of ischemic stroke by enhancing the E-selectin expression.
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Objective To study the expression of vascular endothelial growth factor (VEGF) and its receptors(VEGFR) mRNA at different time points after focal cerebral ischemic-reperfusion(CIR) in rats. Methods Following the establishment of the of transient ischemia modelof middle cerebral artery in rats by Zea-Longa′s method, the expression of VEGF and its receptors mRNA was measured with semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) at different time points. Results The expression of VEGF mRNA increased 3 h after CIR,and peaked at 6 h, and then declined, returned to the baseline at 7 d. The expression of Flt-1 and Flk-1 mRNA was enhanced at 3 h, and reached its peak at 3 d, then declined gradually. Conclusion The expression of VEGF、Flt-1 and Flk-1 mRNA can be induced by focal CIR in rats.
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AIM: To observe clinical efficacy of Tanreqing Injection(Radix Scutellariae,Bear gall powder,Ram's horn,Flos lonicerae japonicae and Fructus forsythiae) in treatment of patients with acute attack of bronchial asthma. METHODS: One hundred and seven patients with an acute asthma were randomly assigned into two groups: a treatment group(n=52,treated by Tanreqing Injection for 10 d in addition to the routine medications) and a control group (n=55,treated by routine medications).The serum levels of ET and TNF-? were determined by radioimmunoassay before and after treatment,respectively. RESULTS: Before treatment,there were no significant differences in the content of serum ET and TNF-? between the treatment group and the control group.However,after 10 d of treatment,the levels of ET and TNF-? in the treatment group were significantly lower than those of the control group(P