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Hsiao-Hsuan Kuo Ran Fan Nina Dvorina Andres Chiesa-Vottero William M. Baldwin III 《Journal of the American Society of Nephrology : JASN》2015,26(4):855-863
Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses. 相似文献
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Kui Li Jiawen Wang Shengxiong Liu Sen Su Chenjian Feng Xiaoxiang Fan Zhiyong Yin 《中华创伤杂志(英文版)》2015,18(2):65-73
Objective: To study the biomechanical mechanism of head injuries beaten with sticks, which is common in the battery or assaultive cases.
Methods: In this study, the Hybrid-III anthropomorphic test device and finite element model (FEM) of the total human model for safety (THUMS) head were used to determine the biomechanical response of head while being beaten with different sticks. Total eight Hybrid-III tests and four finite element simulations were conducted. The contact force, resultant acceleration of head center of gravity, intracranial pressure and von Mises stress were calculated to determine the different biomechanical behavior of head with beaten by different sticks.
Results: In Hybrid-III tests, the stick in each group demonstrated the similar kinematic behavior under the same loading condition. The peak values of the resultant acceleration for thick iron stick group, thin iron stick group, thick wooden stick group and thin wooden stick group were 203.4 g, 221.1 g, 170.5 g and 122.2 g respectively. In finite element simulations, positive intracranial pressure was initially observed in the frontal comparing with negative intracranial pressure in the contra-coup site. Subsequently the intracranial pressure in the coup site was decreasing toward negative value while the contra-coup intracranial pressure increasing toward positive values.
Conclusions: The results illustrated that the stiffer and larger the stick was, the higher the von Mises stress, contact force and intracranial pressure were. We believed that the results in the Hybrid-III tests and THUMS head simulations for brain injury beaten with sticks could be reliable and useful for better understanding the injury mechanism. 相似文献
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目的 探讨血清谷丙转氨酶(ALT)与新诊2型糖尿病(T2DM)患病风险之间的关联,为T2DM的防治提供科学依据。方法 采用4阶段分层随机抽样的方法选取2006年和2009年参与青岛糖尿病预防项目的研究对象男性3 012例、女性4 422例,采用Pearson相关检验分析不同性别ALT与FPG、2 h PG的相关性,并利用多因素logistic回归分析ALT与新诊T2DM患病的关系。结果 男性中,ALT与空腹血浆血糖(FPG)、餐后2 h血浆血糖(2 h PG)的Pearson相关系数分别为0.088、0.080(均P<0.01);多因素logistic回归显示,在调整了年龄、BMI、糖尿病家族史、城乡、教育、婚姻、收入、吸烟及饮酒状况等混杂因素后,ALT的第4分位(Q4)组新诊T2DM患病风险是第1分位(Q1)组的1.832倍(OR = 1.832,95% CI:1.324~2.534,P<0.01)。女性中,ALT与FPG、2h PG的Pearson相关系数分别为0.065、0.108(均P<0.01);多因素logistic回归显示,在调整了年龄、BMI、糖尿病家族史、城乡、教育、婚姻、收入、吸烟及饮酒状况等混杂因素后,ALT的第4分位(Q4)组新诊T2DM患病风险是第1分位(Q1)组的1.445倍(OR = 1.445,95% CI:1.087~1.919,P<0.05)。结论 在男、女性人群中,ALT水平升高与T2DM患病相关,且这种相关性不受年龄、BMI、糖尿病家族史等的影响。 相似文献
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Xue Yao Yan Zhang Jian Hao Hui-Quan Duan Chen-Xi Zhao Chao Sun Bo Li Bao-You Fan Xu Wang Wen-Xiang Li Xuan-Hao Fu Yong Hu Chang Liu Xiao-Hong Kong Shi-Qing Feng 《中国神经再生研究》2019,(3)
Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury. 相似文献
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随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。 相似文献