Longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, calle...Longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, called ischaemia-reperfusion injury(IRI), leads to parenchymal cell death,microcirculatory failure, and inflammatory immune response. Clinically, IRI is the main factor responsible for the occurrence of posttransplant graft dysfunction and ischaemic-type biliary lesions. While extended criteria donor livers are more vulnerable to IRI, their utilisation is required to address the shortfall in donor organs. Thus, the mitigation of IRI should drive the setting of a new benchmark for marginal organ preservation. Herein, strategies incorporating different modalities of machine perfusion of the liver to alleviate IRI are discussed in conjunction with advantages and disadvantages of individual protocols.Techniques leading to reperfusion of the liver during machine perfusion(in situ normothermic regional perfusion and ex situ normothermic machine perfusion)may mitigate IRI by shortening the ischaemic period of the organs. This benefit potentially escalates from the minimum level, obtained following just partial alleviation of the ischaemic period, to the maximum level, which can be potentially achieved with ischaemia-free organ transplantation. Techniques that do not lead to reperfusion of the liver during machine perfusion(hypothermic,subnormothermic, and controlled-oxygenated rewarming) optimise mitochondrial oxidative function and replenish cellular energy stores, thereby lowering reactive oxygen species production as well as the activation ofdownstream inflammatory pathways during reperfusion. Further mechanistic insights into IRI may guide the development of donor-specific protocols of machine perfusion on the basis of the limitations of individual categories of extended criteria donor organs.展开更多
To extend the service life of the clinched joint,a reconditioning process conducted with an additional tubular rivet was proposed in this work.Different reconditioning forces were employed to produce dissimilar recond...To extend the service life of the clinched joint,a reconditioning process conducted with an additional tubular rivet was proposed in this work.Different reconditioning forces were employed to produce dissimilar reconditioned joints by experimental method.The experimental results indicated that the neck fracture was the common failure mode of both original clinched and reconditioned joints.Compared with the original clinched joint,the shearing strength of the reconditioned joint produced by a reconditioning force of 40 kN increased from 1810.5 to 1986.47 N,and the energy absorption increased from 2.34 to 3.46 J.The range of effective reconditioning force was from 35 to 40 kN and 40 kN was the best choice for reconditioning the AA5052 failed joints.The mechanical properties of the reconditioned joints are obviously better than those of the original clinched joints,which fully demonstrates that the reconditioning method proposed in this work has a broad prospect of industrial application.展开更多
基金supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham
文摘Longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, called ischaemia-reperfusion injury(IRI), leads to parenchymal cell death,microcirculatory failure, and inflammatory immune response. Clinically, IRI is the main factor responsible for the occurrence of posttransplant graft dysfunction and ischaemic-type biliary lesions. While extended criteria donor livers are more vulnerable to IRI, their utilisation is required to address the shortfall in donor organs. Thus, the mitigation of IRI should drive the setting of a new benchmark for marginal organ preservation. Herein, strategies incorporating different modalities of machine perfusion of the liver to alleviate IRI are discussed in conjunction with advantages and disadvantages of individual protocols.Techniques leading to reperfusion of the liver during machine perfusion(in situ normothermic regional perfusion and ex situ normothermic machine perfusion)may mitigate IRI by shortening the ischaemic period of the organs. This benefit potentially escalates from the minimum level, obtained following just partial alleviation of the ischaemic period, to the maximum level, which can be potentially achieved with ischaemia-free organ transplantation. Techniques that do not lead to reperfusion of the liver during machine perfusion(hypothermic,subnormothermic, and controlled-oxygenated rewarming) optimise mitochondrial oxidative function and replenish cellular energy stores, thereby lowering reactive oxygen species production as well as the activation ofdownstream inflammatory pathways during reperfusion. Further mechanistic insights into IRI may guide the development of donor-specific protocols of machine perfusion on the basis of the limitations of individual categories of extended criteria donor organs.
基金financial supports from the National Natural Science Foundation of China (No. 51805416)the Young Elite Scientists Sponsorship Program by CAST, China (No. YESS20200279)+3 种基金the Natural Science Foundation of Hunan Province, China (No. 2020JJ5716)the Project of State Key Laboratory of High Performance Complex Manufacturing, Central South University, China (No. ZZYJKT2019-01)the Hunan Provincial Natural Science Foundation for Excellent Young Scholars, China (No. 2021JJ20059)the Huxiang High-Level Talent Gathering Project of Hunan Province, China (No. 2019RS1002)。
文摘To extend the service life of the clinched joint,a reconditioning process conducted with an additional tubular rivet was proposed in this work.Different reconditioning forces were employed to produce dissimilar reconditioned joints by experimental method.The experimental results indicated that the neck fracture was the common failure mode of both original clinched and reconditioned joints.Compared with the original clinched joint,the shearing strength of the reconditioned joint produced by a reconditioning force of 40 kN increased from 1810.5 to 1986.47 N,and the energy absorption increased from 2.34 to 3.46 J.The range of effective reconditioning force was from 35 to 40 kN and 40 kN was the best choice for reconditioning the AA5052 failed joints.The mechanical properties of the reconditioned joints are obviously better than those of the original clinched joints,which fully demonstrates that the reconditioning method proposed in this work has a broad prospect of industrial application.
