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Systematic review of preservation solutions for allografts for heart transplantation based on a network meta-analysisObjective: Currently,the most commonly used method of preservation for transplantation is static cold storage,and the preservation time of allograft is limited to 4-6 h of cold ischemic storage.The preservation of heart allograft plays an essential role in transplantation and has a significant influence on graft function and graft survival,which is essential for long-term survival after transplantation.The most commonly used preservation solutions are the histidine-tryptophan-ketoglutarate solution(HTK),the University of Wisconsin solution(UW)and the Celsior solution.Such trials and studies are often underpowered to identify optimal regimens in these preservation solutions.In this part,we carried out a network-meta analysis of outcomes related to heart transplantation about the outcomes reported by all studies comparing three organ preservation solutions.Methods: Studies were searched in PubMed,Embase,the Cochrane Library,the Transplant Library,and the International Clinical Trials Registry Platform.The final date for literature searches was January 17,2019.Studies of UW solution,HTK solution,and Celsior solution for static cold storage of the heart allografts from adult donors were identified and included.The primary outcome was patient survival at 30 days after heart transplantation.The secondary outcome was the rate of primary graft dysfunction.The Newcastle-Ottawa Scale was applied to assess the quality of nonrandomized controlled studies.The RevMan 5.3 and GeMTC software was used to calculate summary effects for study outcomes.Results: A total of 8 studies were included,of which 2 were compared with HTK solution and Celsior solution,2 with HTK solution and UW solution,and 4 with Celsior solution and UW solution.Compared with HTK and Celsior,UW was associated with significantly improved survival at 30 days(OR = 0.55,95%CI: 0.37-0.69,P < 0.0001;OR = 0.72,95%CI: 0.54-0.94,P = 0.02),but there was no difference between HTK and Celsior solutions.A total of 6,658 patients were enrolled,including 467 patients in the HTK group,2,098 patients in the Celsior group and 4,093 patients in the UW group in the network-meta analysis.Rank-probability test revealed that the hierarchy for 30 days survival(highest to lowest rank)was UW solution,followed by Celsior and HTK solution.The rate of primary graft dysfunction(PGD)after heart transplantation preserved with UW solution was lower than that preserved with Celsior solution(OR = 1.34,95%CI: 1.10-1.62,P = 0.003).A total of 5,600 patients were enrolled,including 244 patients in the HTK group,2,067 patients in the Celsior group and 3,289 patients in the UW group in the network-meta analysis.Rank-probability test revealed that the hierarchy for PGD rate(highest to lowest rank)was HTK solution,followed by Celsior and UW solution.Conclusions: The 30-day survival rate of heart transplant patients preserved with UW solution was higher than that of Celsior solution and HTK solution,and the incidence of primary graft dysfunction was lower than that of Celsior solution and HTK solution.The comparison between the Celsior solution and HTK solution showed that there was no difference in donor heart effect between the two solutions.Reticular Metaanalysis indicated that UW solution was the best for heart preservation,and Celsior solution might be better than HTK solution for heart preservation.Part ? Quantitative proteomic analysis of heart allografts preserved with preservation solutions using iTRAQ labelingObjective: Cardiac preservation solution is mainly composed of different ions,non-permeable substances,energy metabolism substrates,buffer substances,and antioxidants,etc.,and their clinical effects are different.There is no consensus on which cardiac preservation solution has the best effect.The overall level of protein changes under specific conditions is analyzed by proteomics-related technique.In this part,iTRAQ quantitative proteomics technique was used to evaluate the changes of total protein quantity and function in allograft preserved with UW,Celsior and HTK solution.Methods: The twelve Sprague-Dawley(SD)adult male rats were divided into sham-operated group,HTK group,Celsior group and UW group.The allografts were preserved for 6 hours.Proteins were extracted from each group and identified by iTRAQ and mass spectrometry.The differentially identified proteins were analyzed for GO functional annotation,GO enrichment analysis,KEGG functional annotation and KEGG Pathway enrichment,respectively.Results: A total of 1804 proteins were identified,and further differential analysis showed that the total number of differentially expressed proteins in the three preservation solutions was similar.The total number of differentially expressed proteins in UW solution was the lowest,the total number of differentially expressed proteins in HTK solution was the highest,and the Celsior solution was the middle,all the differentially expressed proteins were mainly downregulated.GO functional annotation analysis showed that,compared with the control group,the differentially expressed proteins in the three preservation solutions were mainly related to cell,cell part,organelle,binding,catalytic activity,structural molecule activity,cell process,singleor single-tissue process and metabolic process.GO enrichment analysis showed that the up-regulation of differential proteins in the HTK and Celsior solution was related to oxygen transporter activity,oxygen binding,and heme binding.The down-regulation of proteins in HTK solution was related to histone lysine methylation and histone H3-K4 methylation.The down-regulation of proteins in Celsior were related to the structure,localization,and function of nucleosomes.The down-regulation of differential proteins in UW solution was related to endopeptidase inhibitor activity,endopeptidase inhibitor activity and endopeptidase regulator activity.Compared with the control group,the down-regulation of differential proteins in HTK,Celsior,and UW solutions was associated with protein digestion and absorption,AGE-RAGE signaling pathway in diabetic complications and complement and coagulation cascades,respectively.Conclusions: The differential proteins in the three heart preservation solutions were mainly associated with intracellular nucleosomes and proteasome systems.Downregulation of differential proteins in HTK and Celsior solution involved collagen type I and III,and downregulation of proteins in UW solution involved complement system.Compared with UW solution,both upregulated differentially expressed proteins in HTK solution and Celsior solution may be involved in the activation of Complement and coagulation cascades,and there is a correlation between up-regulation of differential proteins in Celsior solution and HIF-1 signaling pathway.Part ? Effects of cold-inducible RNA-binding protein in the cold stored hearts based on iTRAQ quantitative proteomicsObjective: Except for adding various components to the heart preservation solution to achieve a protective effect,hypothermia is also one of the core points of allograft protection,but the molecular mechanism is not clear.Cold inducible RNAbinding protein(CIRBP)plays an important role in various physiological processes of cells under cold stimulation.This study evaluated the molecular mechanisms involved in CIRBP during donor heart preservation.Methods: Six Sprague-Dawley,Cirbp-/-and Cirbp-Tg adult male rats were selected respectively,and divided into sham operation group,wild-type group,Cirbp-/-group,and p CMV-Cirbp group.The allografts were preserved with UW solution for 6 hours.Proteins were extracted from each group and identified by iTRAQ and mass spectrometry.The differentially identified proteins were screened for GO functional annotation,GO enrichment analysis,KEGG functional annotation and KEGG Pathway enrichment,respectively.Results: A total of 2192 proteins were identified.Differential analysis showed that the down-regulated proteins were the main proteins in UW solution.Compared with the wild-type group,the number of differential proteins in the Cirbp-/-group and p CMVCirbp group changed more,but the down-regulated proteins were the main proteins.Compared with wild-type group,the differential proteins in the Cirbp-/-group and p CMV-Cirbp group mainly involved cell,cell part,organelle,binding,catalytic activity,structural molecule activity,cell process,single-organism process,and metabolic process.GO enrichment analysis showed that the enrichment of down-regulated differential proteins in the Cirbp-/-group was related to the structure,location,and function of nucleosomes.Blood microparticles were mainly enriched in downregulated differential proteins in the p CMV-Cirbp group.KEGG functional annotation analysis showed that,compared with the wild-type group,the up-regulation of differential proteins in the Cirbp-/-group was associated with glycolysis and gluconeogenesis,while the down-regulation of differential proteins in the p CMV-Cirbp group was associated with oxidative phosphorylation.KEGG Pathway enrichment analysis showed that the up-regulated differential proteins in the Cirbp-/-group were Histidine metabolism,Glycine,serine and threonine metabolism,Tryptophan metabolism,Arginine and Proline metabolism and Pyruvate metabolism.In the p CMVCirbp group,down-regulation of differential proteins was associated with galactose metabolism,amino acid sugar and nucleotide sugar metabolism.Conclusions: During the preservation of allografts,CIRBP may participate in DNA damage repair,maintain intracellular energy homeostasis,and reduce reactive oxygen species,and may reduce stress stimulation of cardiomyocytes when it is overexpressed. |
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