为探讨中国汉族人群肿瘤坏死因子受体超家族成员1A基因(tumor necrosis factor receptor superfamily member 1A,TNFRSF1A)rs767455位点多态性(T>C)与脊柱关节病(spondyloarthritides,SpA)患病风险及部分临床指标的关系,采用实时荧...为探讨中国汉族人群肿瘤坏死因子受体超家族成员1A基因(tumor necrosis factor receptor superfamily member 1A,TNFRSF1A)rs767455位点多态性(T>C)与脊柱关节病(spondyloarthritides,SpA)患病风险及部分临床指标的关系,采用实时荧光侵入探针法检测112例SpA患者和82例健康对照的基因型并做关联分析。统计结果显示rs767455位点与SpA患病无显著性关联,但联合中性粒细胞和HLA-B27比单用HLA-B27对SpA发病预测效果更佳(中性粒细胞+HLA-B27 vs HLA-B27,AUC=0.972 vs AUC=0.944,P=0.009)。此外,以本研究样本临床指标均值或中位数作为平均水平分组比较显示,TC型或CC型SpA患者血小板升高的风险显著高于TT型患者(TC+CC vs TT,OR=3.572,95%CI 1.207~10.574,P=0.022),TC型患者血小板高于平均水平的风险同样高于TT型患者(TC vs TT,OR=3.907,95%CI 1.195~12.778,P=0.024)。相对于携带T等位基因患者,C等位基因携带者血小板数目(C vs T,OR=3.000,95%CI 1.143~7.871,P=0.026)、单核细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)和中性粒细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)高于平均水平的风险显著升高。在不同组织或细胞样本中的连锁分析显示rs767455是TNFRSF1A的剪接数量性状位点(splicing quantitative trait locus,sQTL)。该研究提示,中性粒细胞可能独立于HLA-B27参与SpA的发病,rs767455位点C等位基因可能通过影响可变剪接参与TNFRSF1A的调控,引起SpA患者中性粒细胞水平升高为代表的免疫失衡,对SpA的致病机制研究和临床精准治疗具有一定指导意义。展开更多
Objective： To study the effect of Wenhua Juanbi Recipe（温化蠲痹方, WJR） on expression of receptor activator of nuclear factor kappa B ligand（RANKL）, osteoprotegerin（OPG）, and tumor necrosis factor receptor supe...Objective： To study the effect of Wenhua Juanbi Recipe（温化蠲痹方, WJR） on expression of receptor activator of nuclear factor kappa B ligand（RANKL）, osteoprotegerin（OPG）, and tumor necrosis factor receptor superfamily member 14（TNFRSF14, also known as LIGHT） in rats with collagen-induced arthritis（CIA）. Methods： CIA rats were generated by subcutaneous injection of bovine collagen type-Ⅱ at the tail base. Sixty CIA rats were randomly assigned（10 animals/group） to： model, methotrexate（MTX）-treated（0.78 mg/kg body weight）, and WJR-treated（22.9 g/kg） groups. Healthy normal rats（n=10） were used as the normal control. Treatments or saline were administered once daily by oral gavage. Rats were sacrificed at day 28 post-treatment and knee synovium and peripheral blood serum were collected. Toe swelling degree and expression of RANKL, OPG, and LIGHT were determined by Western blot and immunohistochemistry. Results： Compared with the normal group, toe swelling degree was significantly increased in the model group（P〈0.01）. After treatment, toe swelling degree decreased significantly in the WJR and MTX groups compared with the model group（P〈0.01）. Compared with the normal group, expression of RANKL and LIGHT were significantly increased and OPG significantly decreased in peripheral blood and synovium of the model group（P〈0.01）. Conversely, RANKL and LIGHT expression were significantly reduced and OPG increased in the WJR and MTX groups compared with the model group（P〈0.01）. No statistically significant difference existed between WJR and MTX groups. Conclusion： WJR likely acts by reducing RANKL expression and increasing OPG expression, thus inhibiting RANKL/RANK interaction and reducing LIGHT expression, thereby inhibiting osteoclast formation/activation to block bone erosion.展开更多
BACKGROUND： Inflammatory reaction correlates with sporadic intracranial aneurysm （IA）. Variation of tumor necrosis factor receptor superfamily 13B （TNFRSF13B）, an inflammatory mediator receptor, may associate wit...BACKGROUND： Inflammatory reaction correlates with sporadic intracranial aneurysm （IA）. Variation of tumor necrosis factor receptor superfamily 13B （TNFRSF13B）, an inflammatory mediator receptor, may associate with IA. OBJECTIVE： To explore the relationship between TNFRSF13B gene and sporadic IA, as well as the clinical characteristics of sporadic IA. DESIGN, TIME AND SETTING： Case-control study of genetic association was performed at the Experimental Technology Center of China Medical University from November 2006 to January 2008. PARTICIPANTS： A total of 367 patients with IA, confirmed by three-dimensional computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, and neuro surgery, were admitted to the Department of Neurosurgery, First Affiliated Hospital of China Medical University from 2006 to 2007, and were selected as the case group. All patients were Han, with no family history of IA. In addition, a total of 396 non-lA patients were selected as control subjects. METHODS： Peripheral vein blood was harvested to extract whole blood genomic DNA. Genotyping and TNFRSF13B single nucleotide polymorphism （SNP） rs11078355 G〉A allele polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. The relationship of TNFRSF13B SNP rs11078355 G〉A polymorphisms to IA and IA clinical characteristics were analyzed using the chi-square and two-sided test. MAIN OUTCOME MEASURES： TNFRSF13B SNP rs11078355 G〉A genotype distribution. RESULTS： In the IA patients, TNFRSF13B SNP rs11078355 G〉A genotype frequency was significantly increased （X2 = 16.306, odds ratio = 1.881,95% confidence interval = 1.382 2.560, P 〈 0.001）. In IA patients aged 〉 65 years, the frequency of TNFRSF13B SNP rs11078355 GA ＋ AA genotype was significantly greater than the GG genotype （X2 = 26.604, odds ratio = 5.248, 95% confidence interval = 2.662 10.345, P 〈 0.001）. CONCLUSION： The TNFRSF13B gene may associate with sporadic IA i展开更多
文摘为探讨中国汉族人群肿瘤坏死因子受体超家族成员1A基因(tumor necrosis factor receptor superfamily member 1A,TNFRSF1A)rs767455位点多态性(T>C)与脊柱关节病(spondyloarthritides,SpA)患病风险及部分临床指标的关系,采用实时荧光侵入探针法检测112例SpA患者和82例健康对照的基因型并做关联分析。统计结果显示rs767455位点与SpA患病无显著性关联,但联合中性粒细胞和HLA-B27比单用HLA-B27对SpA发病预测效果更佳(中性粒细胞+HLA-B27 vs HLA-B27,AUC=0.972 vs AUC=0.944,P=0.009)。此外,以本研究样本临床指标均值或中位数作为平均水平分组比较显示,TC型或CC型SpA患者血小板升高的风险显著高于TT型患者(TC+CC vs TT,OR=3.572,95%CI 1.207~10.574,P=0.022),TC型患者血小板高于平均水平的风险同样高于TT型患者(TC vs TT,OR=3.907,95%CI 1.195~12.778,P=0.024)。相对于携带T等位基因患者,C等位基因携带者血小板数目(C vs T,OR=3.000,95%CI 1.143~7.871,P=0.026)、单核细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)和中性粒细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)高于平均水平的风险显著升高。在不同组织或细胞样本中的连锁分析显示rs767455是TNFRSF1A的剪接数量性状位点(splicing quantitative trait locus,sQTL)。该研究提示,中性粒细胞可能独立于HLA-B27参与SpA的发病,rs767455位点C等位基因可能通过影响可变剪接参与TNFRSF1A的调控,引起SpA患者中性粒细胞水平升高为代表的免疫失衡,对SpA的致病机制研究和临床精准治疗具有一定指导意义。
基金Supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY12H29008)the Zhejiang Provincial Project of Traditional Chinese Medicine Science and Technology Plan(No.2008CA086,2009CB195,2012ZB121,2015ZA143)+1 种基金the Hangzhou Health Science and Technology Plan(No.2010B027,No.2014A37)the Hangzhou Social Development Plan(No.20120633B12,No.20160533B45)
文摘Objective： To study the effect of Wenhua Juanbi Recipe（温化蠲痹方, WJR） on expression of receptor activator of nuclear factor kappa B ligand（RANKL）, osteoprotegerin（OPG）, and tumor necrosis factor receptor superfamily member 14（TNFRSF14, also known as LIGHT） in rats with collagen-induced arthritis（CIA）. Methods： CIA rats were generated by subcutaneous injection of bovine collagen type-Ⅱ at the tail base. Sixty CIA rats were randomly assigned（10 animals/group） to： model, methotrexate（MTX）-treated（0.78 mg/kg body weight）, and WJR-treated（22.9 g/kg） groups. Healthy normal rats（n=10） were used as the normal control. Treatments or saline were administered once daily by oral gavage. Rats were sacrificed at day 28 post-treatment and knee synovium and peripheral blood serum were collected. Toe swelling degree and expression of RANKL, OPG, and LIGHT were determined by Western blot and immunohistochemistry. Results： Compared with the normal group, toe swelling degree was significantly increased in the model group（P〈0.01）. After treatment, toe swelling degree decreased significantly in the WJR and MTX groups compared with the model group（P〈0.01）. Compared with the normal group, expression of RANKL and LIGHT were significantly increased and OPG significantly decreased in peripheral blood and synovium of the model group（P〈0.01）. Conversely, RANKL and LIGHT expression were significantly reduced and OPG increased in the WJR and MTX groups compared with the model group（P〈0.01）. No statistically significant difference existed between WJR and MTX groups. Conclusion： WJR likely acts by reducing RANKL expression and increasing OPG expression, thus inhibiting RANKL/RANK interaction and reducing LIGHT expression, thereby inhibiting osteoclast formation/activation to block bone erosion.
文摘BACKGROUND： Inflammatory reaction correlates with sporadic intracranial aneurysm （IA）. Variation of tumor necrosis factor receptor superfamily 13B （TNFRSF13B）, an inflammatory mediator receptor, may associate with IA. OBJECTIVE： To explore the relationship between TNFRSF13B gene and sporadic IA, as well as the clinical characteristics of sporadic IA. DESIGN, TIME AND SETTING： Case-control study of genetic association was performed at the Experimental Technology Center of China Medical University from November 2006 to January 2008. PARTICIPANTS： A total of 367 patients with IA, confirmed by three-dimensional computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, and neuro surgery, were admitted to the Department of Neurosurgery, First Affiliated Hospital of China Medical University from 2006 to 2007, and were selected as the case group. All patients were Han, with no family history of IA. In addition, a total of 396 non-lA patients were selected as control subjects. METHODS： Peripheral vein blood was harvested to extract whole blood genomic DNA. Genotyping and TNFRSF13B single nucleotide polymorphism （SNP） rs11078355 G〉A allele polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. The relationship of TNFRSF13B SNP rs11078355 G〉A polymorphisms to IA and IA clinical characteristics were analyzed using the chi-square and two-sided test. MAIN OUTCOME MEASURES： TNFRSF13B SNP rs11078355 G〉A genotype distribution. RESULTS： In the IA patients, TNFRSF13B SNP rs11078355 G〉A genotype frequency was significantly increased （X2 = 16.306, odds ratio = 1.881,95% confidence interval = 1.382 2.560, P 〈 0.001）. In IA patients aged 〉 65 years, the frequency of TNFRSF13B SNP rs11078355 GA ＋ AA genotype was significantly greater than the GG genotype （X2 = 26.604, odds ratio = 5.248, 95% confidence interval = 2.662 10.345, P 〈 0.001）. CONCLUSION： The TNFRSF13B gene may associate with sporadic IA i
