Through studies on the element geochemistry, alteration of country rocks, ore-forming fluids and isotopegeochemistry of the Arno tin deposit in the metamorphic rocks of the Upper Proterozoic Ximeng Group, theauthors c...Through studies on the element geochemistry, alteration of country rocks, ore-forming fluids and isotopegeochemistry of the Arno tin deposit in the metamorphic rocks of the Upper Proterozoic Ximeng Group, theauthors consider that the concentration of the B-F-Li-Rb-Cs-Sn association is related to acidic magmatism inthe study area. The Fe-Mg-Li tourmaline in the ore is the replaced product of the country rocks byhypothermal fluid. The δ^(18)O values of mineral separates are +2.01- +13.16‰ and their δ^(34)S values, +2.6-+7.2‰. The ore-forming materials were derived from hydrothermal fluid of granitic magma. For themineralization, the temperature is 450°-350℃, the pressure, 450-1000×10~5 Pa, and the age, Himalayan(21.5 Ma). According to the geochemical characteristics, a minerogenic model is established: the deposit is ahypothermal cassiterite-quartz vein type tin deposit controlled by the hidden Himalayan granites.展开更多
By visualizing DNA with diamidino phenylindole (DAPI), we found that hypothermal incubation followed by rewarming of human neutrophils resulted in an increased number of DAPI-positive objects representative of extensi...By visualizing DNA with diamidino phenylindole (DAPI), we found that hypothermal incubation followed by rewarming of human neutrophils resulted in an increased number of DAPI-positive objects representative of extensive DNA unfolding seemingly similar to neutrophil extracellular traps (NETs). In contrast to canonical NET formation, diphenylene iodonium (DPI), an NADPH oxidase inhibitor, exhibited negligible effects on formation of the DAPI-positive objects. Moreover, multiple instances of DNA damage were detected in the objects, but not in canonical NETs. Our results thus suggest the potential of hypothermia for triggering DNA structural alteration in neutrophils, which is similar to but distinct from NET formation.展开更多
The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic aci...The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid(5-ALA).Furthermore,this study aimed to explore the underlying mechanism of the protective effects of 5-ALA.First,we collected and stored mouse testicular fragments in different media,including Hank’s balanced salt solution(HBSS;n=5),Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12(DMEM/F12;n=5),and alpha-minimum essential medium(αMEM;n=5).Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group(P<0.05)and theαMEM group(P<0.01).Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA(0[control],1 mmol l−1,2 mmol l−1,and 5 mmol l−1)to determine the most effective concentration of 5-ALA.The 2 mmol l−15-ALA group(n=3)presented the highest positive rate of spermatogonial stem cells compared with those in the control,1 mmol l−1,and 5 mmol l−15-ALA groups.Finally,the tissue fragments were preserved in HBSS with control(n=3)and 2 mmol l−15-ALA(n=3)under low-temperature conditions.A comparative analysis was performed against fresh testes(n=3)to elucidate the underlying mechanism of 5-ALA.Gene set enrichment analysis(GSEA)for WikiPathways revealed that the p38 mitogen-activated protein kinase(MAPK)signaling pathway was downregulated in the 2 mmol l−15-ALA group compared with that in the control group(normalized enrichment score[NES]=−1.57,false discovery rate[FDR]=0.229,and P=0.019).In conclusion,these data suggest that using 2 mmol l−15-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.展开更多
Background:The use of grafts from donation after circulatory death(DCD)overcomes the inadequate donor organ supply.Our team developed a transportable dual hypothermic oxygenated machine perfusion(DHOPE)device,which in...Background:The use of grafts from donation after circulatory death(DCD)overcomes the inadequate donor organ supply.Our team developed a transportable dual hypothermic oxygenated machine perfusion(DHOPE)device,which initiates DHOPE at a recipient center to reduce static cold storage(SCS)time and the risk of graft failure in DCD liver transplantation.Methods:Six porcine livers per group with 30 min of warm ischemia exposure were preserved via SCS or DHOPE for 6 h and then reperfused for 12 h with whole blood to mimic transplantation.Hepatocellular and biliary function and injury were assessed in perfusate and bile samples.Molecular biomarkers and histology were compared between groups.Results:Reperfusion portal vein pressure,in a flow-constant manner,and alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)and gamma-glutamyltransferase(γ-GGT)release were significantly lower in the DHOPE group than in the SCS group at all time points.Higher bile production paralleled the lower levels of ALP andγ-GGT in the DHOPE group.The DHOPE group secreted more total bilirubin(TBIL)in bile,resulting in decreased TBIL in the perfusate,and livers preserved with DHOPE exhibited better cholangiocellular function.Furthermore,improvements in hypoxia,the inflammatory response,cell-free microRNAs and energy metabolism were observed in the DHOPE group.There were fewer apoptotic cells and TGF-β1-positive cells in the liver parenchyma and extrahepatic bile duct in the DHOPE group than in the SCS group.Conclusions:This study demonstrates the efficacy of local 4℃DHOPE to protect porcine liver grafts from30-min warm ischemia damage.展开更多
Post-reperfusion syndrome(PRS)in liver transplant recipients remains one of the most dreaded complications in liver transplant surgery.PRS can impact the short-term and long-term patient and graft outcomes.The definit...Post-reperfusion syndrome(PRS)in liver transplant recipients remains one of the most dreaded complications in liver transplant surgery.PRS can impact the short-term and long-term patient and graft outcomes.The definition of PRS has evolved over the years,from changes in arterial blood pressures and heart and/or de-creases in the systemic vascular resistance and cardiac output to including the fibrinolysis and grading the severity of PRS.However,all that did not reflect on the management of PRS or its impact on the outcomes.In recent years,new scientific techniques and new technology have been in the pipeline to better understand,manage and maybe prevent PRS.These new methods and techniques are still in the infancy,and they have to be proven not in prevention and management of PRS but their effects in the patient and graft outcomes.In this article,we will review the long history of PRS,its definition,etiology,mana-gement and most importantly the new advances in science and technology to prevent and properly manage PRS.展开更多
BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive...BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive strategy to expand the donor pool and reduce waitlist times.Given increased risk of cold ischemia time with SLT,machine perfusion represents a promising option to reduce it and optimize transplant logistics and outcomes.The present communication describes various possible combinations of procurement steps to perform SLT facilitated by placing one or both grafts on a normothermic machine perfusion(NMP)closed circuit device.CASE SUMMARY A 19-month-old female with biliary atresia after failed Kasai portoenterostomy and a 42-year-old woman with unresectable intrahepatic cholangiocarcinoma were selected as recipients for a SLT from a 17-year-old male donor.The SLT generated a left lateral segment and a right trisectional graft of appropriate volume for both recipients.After a mixed in-situ and ex-situ split,in order to improve logistics,the right trisectional graft was placed on a closed circuit NMP device,following an appropriate vascular reconstruction.Both grafts were implanted with excellent short-term outcomes.CONCLUSION Use of NMP with SLT for preservation prior to implantation allows not only for graft optimization but also for significant improvement of transplant logistics.We propose various models and standardization of logistic options for combining SLT with NMP to optimize graft availability and outcomes.展开更多
Objective To investigate the expression of nerve growth factor （NGF） and glial cell line-derived neurotrophic factor （GDNF） in monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood ...Objective To investigate the expression of nerve growth factor （NGF） and glial cell line-derived neurotrophic factor （GDNF） in monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. Methods The monkeys were immediately removed brain after death in operation of group A （identical temperature perfusion group） and group B （ultraprofound hypothermia perfusion group）. Immunohistochemical technique was used to determine frontal cellular expression of NGF and GDNF. Statistics were analyzed by ANOVA analyses with significance level at P 〈 0.05. Results The expressions of NGF and GDNF in the group B were significantly higher than those in the group A （P 〈 0.05）. Conclusion NGF and GDNF increased significantly in the monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. It may be a protective mechanism for neuron survival and neural function recovery.展开更多
The Qilishan gold deposit is located in the southern Zhaolai gold ore belt in the northwestern Jiaodong region.A total of seven gold ore bodies have been found in the mining area.Linglong gneissic biotite granite and ...The Qilishan gold deposit is located in the southern Zhaolai gold ore belt in the northwestern Jiaodong region.A total of seven gold ore bodies have been found in the mining area.Linglong gneissic biotite granite and the NE trending Lingbei fracture control the output and distribution of the gold deposit.The ore bodies with veined or irregular shape occur in the structural alteration zone.The ore bodies of different sizes are NE trending and SE dipping.The constituent minerals of the ores mainly include pyrite,chalcopyrite,native gold,electrum,argentite,matildite,hematite,quartz and calcite.The ores are characterized by metasomatic dissolution structure,as well as veined and brecciated structures.The ore-forming process is divided into four stages,namely quartz-,pyrite-,polymetallic-and carbonate stages.Study on fluid inclusion shows that the deposit is composed of gas-liquid two-phase inclusions （Ⅰ） and three-phase inclusions containing CO2 （Ⅱ）,and that the former dominates.The homogenization temperature is 259.6℃-373.7℃ ; the salinity of three-phase inclusions containing CO2is 5.77%-9.84% （NaCl） ; the salinity of gas-liquid two-phase inclusions is 6.58%-8.54% （NaCl） ; and the estimated ore-forming pressure is 55.2-82.2 MPa.According to the nonlinear relationship between the depth and pressure of the fluid in the fracture zone,the ore-forming depth of the Qilishan gold deposit is calculated as 5.95-7.14 km.It is preliminarily determined that the deposit is a mesophilic and hypothermal gold deposit.展开更多
AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin col...AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best(vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001).CONCLUSION: HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP.展开更多
Oxidative stress and apoptosis are the key factors that limit the hypothermic preservation time of donor hearts to within 4–6 h.The aim of this study was to investigate whether the histone deacetylase 3(HDAC3)inhibit...Oxidative stress and apoptosis are the key factors that limit the hypothermic preservation time of donor hearts to within 4–6 h.The aim of this study was to investigate whether the histone deacetylase 3(HDAC3)inhibitor RmGodFyPn9 a6 m6 i cc opualrda mpreotteercst daugrianing srt ecpaerrdfiuasci oinn juwreyr ei nedvuacleuda tebyd.pTrholeo nexgperde shsyipoont haenrdm pich opsrpehsoerryvlaattiioonn.leRvaet lsh eoaf rtms awmemrea lihayn-??STE20-like kinase-1(Mst1)and Yes-associated protein(YAP)were determined by western blotting.Cell apoptosis was measured by the terminal deoxynucleotidyl-transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)method.Addition of RGFP966 in Celsior solution significantly inhibited cardiac dysfunction induced by hypothermic preservation.RGFP966 inhibited the hypothermic preservation-induced increase of the phosphorylated(p)-Mst1/Mst1 and p-YAP/YAP ratios,prevented a reduction in total YAP protein expression,and increased the nuclear YAP protein level.Verteporfin(VP),a small molecular inhibitor of YAP–transcriptional enhanced associate domain(TEAD)interaction,partially abolished the protective effect of RGFP966 on cardiac function,and reduced lactate dehydrogenase activity and malondialdehyde content.RGFP966 increased superoxide dismutase,catalase,and glutathione peroxidase gene and protein expression,which was abolished by VP.RGFP966 inhibited hypothermic preservation-induced overexpression of B-cell lymphoma protein 2(Bcl-2)-associated X(Bax)and cleaved caspase-3,increased Bcl-2 mRNA and protein expression,and reduced cardiomyocyte apoptosis.The antioxidant and anti-apoptotic effects of RGFP966 were cancelled by VP.The results suggest that supplementation of Celsior solution with RGFP966 attenuated prolonged hypothermic preservation-induced cardiac dysfunction.The mechanism may involve inhibition of oxidative stress and apoptosis via inactivation of the YAP pathway.展开更多
Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulat...Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulatory arrest are unclear. After piglet models underwent 60 minutes of deep hypothermic circulatory arrest at 14°C, expression of microRNAs(miRNAs) was analyzed in the hippocampus by microarray. Subsequently, TargetScan 6.2, RNA22 v2.0, miRWalk 2.0, and miRanda were used to predict potential targets, and gene ontology enrichment analysis was carried out to identify functional pathways involved. Quantitative reverse transcription-polymerase chain reaction was conducted to verify miRNA changes. Deep hypothermic circulatory arrest altered the expression of 35 miRNAs. Twenty-two miRNAs were significantly downregulated and thirteen miRNAs were significantly upregulated in the hippocampus after deep hypothermic circulatory arrest. Six out of eight targets among the differentially expressed miRNAs were enriched for neuronal projection(cyclin dependent kinase, CDK16 and SLC1 A2), central nervous system development(FOXO3, TYRO3, and SLC1 A2), ion transmembrane transporter activity(ATP2 B2 and SLC1 A2), and interleukin-6 receptor binding(IL6 R)– these are the key functional pathways involved in cerebral protection during deep hypothermic circulatory arrest. Quantitative reverse transcription-polymerase chain reaction confirmed the results of microarray analysis. Our experimental results illustrate a new role for transcriptional regulation in deep hypothermic circulatory arrest, and provide significant insight for the development of miRNAs to treat brain injuries. All procedures were approved by the Animal Care Committee of Xuanwu Hospital, Capital Medical University, China on March 1, 2017(approval No. XW-INI-AD2017-0112).展开更多
The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to red...The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.展开更多
AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex...AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion(HMP).METHODS Eighteen young(4 mo old) and 18 aged(17 mo old)healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group(UWP), and UW solution with metformin perfusion group(MUWP). Aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), interleukin-18(IL-18), and tumor necrosis factor-alpha(TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase(e NOS) in liver sinusoidal endothelial cells were also examined.Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done. RESULTS AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively,significantly lower in the MUWP group than in the UWP group(P < 0.05), but no significant differences were found between the young and aged MUWP groups.Metformin increased the expression of AMPK and e NOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-e NOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.CONCLUSION The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.展开更多
Acute-on-chronic liver failure(ACLF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term mortality.Partially due to the lack o...Acute-on-chronic liver failure(ACLF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term mortality.Partially due to the lack of universal diagnostic criteria,the actual ACLF prevalence remains unclear;nevertheless,it is expected to be a highly prevalent condition worldwide.Earlier transplantation is an effective protective measure for selected ACLF patients.Besides liver transplantation,diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy.Although new clinical specific therapies have been researched,more studies are necessary to assess safety and efficacy.Therefore,future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow.Thus,an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality.In addition,while donor organ quality is meant to be a prognostic factor in the ACLF setting,recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.展开更多
The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by ...The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.展开更多
The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or earl...The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.展开更多
The technique for bloodless hepatic resection using the total hepatic vascular isolation under the normothermic or hypothermic perfusion was reported to deal with the large liver tumor involving in the liver hilum,the...The technique for bloodless hepatic resection using the total hepatic vascular isolation under the normothermic or hypothermic perfusion was reported to deal with the large liver tumor involving in the liver hilum,the main hepatic veins or the retrohepatic vena cava.The original Heaney's and Fortner's methods were modified so that the technique could be simpler and more practicable to perform otherwise hazardous liver resection.During the past 4 year,major hepatic resection with the normothermic or hypothermic total vascular exclusion technique was successfully performed on 19 patients with liver tumors in our department.Among the 19 cases,16 underwent hepatic resection with the normothermic selective total vascular exclusion(extended right lobectomy in 5 cases,extended left lobectomy in 3 cases;right lobectomy in 5 cases;central segmentectomy in 3 cases)and 3 with the total vascular isolation and in situ cold perfusion(extended left lobectomy in 2 case,extended right lobectong in 1case).We believe that the technique of normothermic vascular exclusion may be indicated to deal with the lesion close to the hepatic veins and the retrohepatic vena cava.However,for more complicated hepatic resection,the hypothermic perfusion technique should be considered to prolong the safety of ischemic tune of the liver.The preliminary experience in the clinical application using the above technique is reported.展开更多
This study was undertaken to analyze the perioperative factors and complications that influence the final outcome after deep hypothermic circulatory arrest and superficial hypothermia during operations on aortic aneur...This study was undertaken to analyze the perioperative factors and complications that influence the final outcome after deep hypothermic circulatory arrest and superficial hypothermia during operations on aortic aneurysms from Jan 2000 to Jun 2004. The results show that deep hypthermic circulatory arrest group provided a high risk of pulmonary insufficiency-hypoxemia and temporary neurological dysfunction in complication but not increased the risk of hospital mortality.展开更多
BACKGROUND Persistent left superior vena cava(PLSVC),a relatively rare thoracic vascular malformation,can inconvenience perfusionists and operators when encountered during deep hypothermic circulatory arrest(DHCA).CAS...BACKGROUND Persistent left superior vena cava(PLSVC),a relatively rare thoracic vascular malformation,can inconvenience perfusionists and operators when encountered during deep hypothermic circulatory arrest(DHCA).CASE SUMMARY Herein,we describe the case of a patient with concurrent giant aortic arch aneurysm,aortic stenosis,and PLSVC.To treat these conditions,we performed right hemiarch and aortic valve replacements under DHCA.Notably,we applied“bilateral superior vena cava retrograde cerebral perfusion(RCP)”for cerebral protection,which significantly optimized the surgical procedure and reduced the risk of postoperative complications.The patient was discharged 14 d after surgery with no complications.CONCLUSION Surgical intervention for PLSVC under DHCA can be performed using the bilateral superior vena cava RCP approach.展开更多
Background: In clinical and basic science medicine, we often isolate ourselves in silos, unaware of developments in other related disciplines. Our team has had substantial experience, both in the operating room and in...Background: In clinical and basic science medicine, we often isolate ourselves in silos, unaware of developments in other related disciplines. Our team has had substantial experience, both in the operating room and in the laboratory, with protecting the brain and the spinal cord via hypothermia. Herein, we briefly share this experience with our colleagues in Neurology, eager for comments and advice from the neurologic perspective. Methods: 1) Clinical brain protection via deep hypothermic circulatory arrest (DHCA) for surgery of the aortic arch. For aortic arch replacement (performed for aortic arch aneurysm or aortic dissection), the aortic arch must be opened and native perfusion stopped. We have decades of experience in many hundreds of patients with this technique. This experience is reviewed. 2) Experimental protection of the spinal cord via cooling. We review our laboratory experience with a novel, recirculating cooling catheter for the vulnerable spinal cord. 3) Experimental protection of the brain via an intraventricular cooling catheter. We review our laboratory experience cooling the brain with a balloon-tipped catheter residing the lateral ventricles. Results: 1) Deep hypothermic circulatory arrest for aortic arch surgery provides superb brain protection for periods up to 45 minutes or longer. Clinical neurologic function, and quantitative neurologic tests, show excellent brain preservation. 2) The novel spinal cooling catheter provides excellent cooling of the spinal cord in a large animal model, without apparent injury of any type. 3) The intraventricular brain cooling catheter provides excellent cooling of the brain, documented by both direct temperature probe and high-tech brain imaging. Conclusions: We wish herein (in this article) to share this experience across our disciplines (Cardiac Surgery and Neurology). We welcome advice from the Neurology community on these surgically-directed methods for cooling and protection of neurological tissue in both the brain and the spinal cord.展开更多
文摘Through studies on the element geochemistry, alteration of country rocks, ore-forming fluids and isotopegeochemistry of the Arno tin deposit in the metamorphic rocks of the Upper Proterozoic Ximeng Group, theauthors consider that the concentration of the B-F-Li-Rb-Cs-Sn association is related to acidic magmatism inthe study area. The Fe-Mg-Li tourmaline in the ore is the replaced product of the country rocks byhypothermal fluid. The δ^(18)O values of mineral separates are +2.01- +13.16‰ and their δ^(34)S values, +2.6-+7.2‰. The ore-forming materials were derived from hydrothermal fluid of granitic magma. For themineralization, the temperature is 450°-350℃, the pressure, 450-1000×10~5 Pa, and the age, Himalayan(21.5 Ma). According to the geochemical characteristics, a minerogenic model is established: the deposit is ahypothermal cassiterite-quartz vein type tin deposit controlled by the hidden Himalayan granites.
文摘By visualizing DNA with diamidino phenylindole (DAPI), we found that hypothermal incubation followed by rewarming of human neutrophils resulted in an increased number of DAPI-positive objects representative of extensive DNA unfolding seemingly similar to neutrophil extracellular traps (NETs). In contrast to canonical NET formation, diphenylene iodonium (DPI), an NADPH oxidase inhibitor, exhibited negligible effects on formation of the DAPI-positive objects. Moreover, multiple instances of DNA damage were detected in the objects, but not in canonical NETs. Our results thus suggest the potential of hypothermia for triggering DNA structural alteration in neutrophils, which is similar to but distinct from NET formation.
基金funded by the National Natural Science Foundation of China(No.81971759 and No.82171604)the Guangdong Basic and Applied Basic Research Foundation(2023B1515020108)+3 种基金the Science and Technology Program of Guangzhou(202206010089)the Excellent Talents Training Project of The Sixth Affiliated Hospital of Sun Yat-sen University(R20210217202601970)the Postdoctoral Fellowship Program of CPSF(GZC20233216)the Basic and Applied Basic Research Foundation of Guangdong Province(2021A1515111195).
文摘The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid(5-ALA).Furthermore,this study aimed to explore the underlying mechanism of the protective effects of 5-ALA.First,we collected and stored mouse testicular fragments in different media,including Hank’s balanced salt solution(HBSS;n=5),Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12(DMEM/F12;n=5),and alpha-minimum essential medium(αMEM;n=5).Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group(P<0.05)and theαMEM group(P<0.01).Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA(0[control],1 mmol l−1,2 mmol l−1,and 5 mmol l−1)to determine the most effective concentration of 5-ALA.The 2 mmol l−15-ALA group(n=3)presented the highest positive rate of spermatogonial stem cells compared with those in the control,1 mmol l−1,and 5 mmol l−15-ALA groups.Finally,the tissue fragments were preserved in HBSS with control(n=3)and 2 mmol l−15-ALA(n=3)under low-temperature conditions.A comparative analysis was performed against fresh testes(n=3)to elucidate the underlying mechanism of 5-ALA.Gene set enrichment analysis(GSEA)for WikiPathways revealed that the p38 mitogen-activated protein kinase(MAPK)signaling pathway was downregulated in the 2 mmol l−15-ALA group compared with that in the control group(normalized enrichment score[NES]=−1.57,false discovery rate[FDR]=0.229,and P=0.019).In conclusion,these data suggest that using 2 mmol l−15-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
基金supported by grants from 2020 Guangdong Provincial and Municipal Joint Fund For Basic and Applied Basic Research Project(2020B1515120031)2020 Foshan Municipal Deng Fang Distinguished Research Program(2020A007)+2 种基金Key Scientific Research Program for the development of Ex vivo Liver Perfusion System of Foshan City,China[(2019)No.42]Science and Technol-ogy Program of Guangzhou(202002030201)Guangzhou Sci-ence and Technology Plan(2025A04J3674)。
文摘Background:The use of grafts from donation after circulatory death(DCD)overcomes the inadequate donor organ supply.Our team developed a transportable dual hypothermic oxygenated machine perfusion(DHOPE)device,which initiates DHOPE at a recipient center to reduce static cold storage(SCS)time and the risk of graft failure in DCD liver transplantation.Methods:Six porcine livers per group with 30 min of warm ischemia exposure were preserved via SCS or DHOPE for 6 h and then reperfused for 12 h with whole blood to mimic transplantation.Hepatocellular and biliary function and injury were assessed in perfusate and bile samples.Molecular biomarkers and histology were compared between groups.Results:Reperfusion portal vein pressure,in a flow-constant manner,and alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)and gamma-glutamyltransferase(γ-GGT)release were significantly lower in the DHOPE group than in the SCS group at all time points.Higher bile production paralleled the lower levels of ALP andγ-GGT in the DHOPE group.The DHOPE group secreted more total bilirubin(TBIL)in bile,resulting in decreased TBIL in the perfusate,and livers preserved with DHOPE exhibited better cholangiocellular function.Furthermore,improvements in hypoxia,the inflammatory response,cell-free microRNAs and energy metabolism were observed in the DHOPE group.There were fewer apoptotic cells and TGF-β1-positive cells in the liver parenchyma and extrahepatic bile duct in the DHOPE group than in the SCS group.Conclusions:This study demonstrates the efficacy of local 4℃DHOPE to protect porcine liver grafts from30-min warm ischemia damage.
文摘Post-reperfusion syndrome(PRS)in liver transplant recipients remains one of the most dreaded complications in liver transplant surgery.PRS can impact the short-term and long-term patient and graft outcomes.The definition of PRS has evolved over the years,from changes in arterial blood pressures and heart and/or de-creases in the systemic vascular resistance and cardiac output to including the fibrinolysis and grading the severity of PRS.However,all that did not reflect on the management of PRS or its impact on the outcomes.In recent years,new scientific techniques and new technology have been in the pipeline to better understand,manage and maybe prevent PRS.These new methods and techniques are still in the infancy,and they have to be proven not in prevention and management of PRS but their effects in the patient and graft outcomes.In this article,we will review the long history of PRS,its definition,etiology,mana-gement and most importantly the new advances in science and technology to prevent and properly manage PRS.
文摘BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive strategy to expand the donor pool and reduce waitlist times.Given increased risk of cold ischemia time with SLT,machine perfusion represents a promising option to reduce it and optimize transplant logistics and outcomes.The present communication describes various possible combinations of procurement steps to perform SLT facilitated by placing one or both grafts on a normothermic machine perfusion(NMP)closed circuit device.CASE SUMMARY A 19-month-old female with biliary atresia after failed Kasai portoenterostomy and a 42-year-old woman with unresectable intrahepatic cholangiocarcinoma were selected as recipients for a SLT from a 17-year-old male donor.The SLT generated a left lateral segment and a right trisectional graft of appropriate volume for both recipients.After a mixed in-situ and ex-situ split,in order to improve logistics,the right trisectional graft was placed on a closed circuit NMP device,following an appropriate vascular reconstruction.Both grafts were implanted with excellent short-term outcomes.CONCLUSION Use of NMP with SLT for preservation prior to implantation allows not only for graft optimization but also for significant improvement of transplant logistics.We propose various models and standardization of logistic options for combining SLT with NMP to optimize graft availability and outcomes.
基金This work was supported by the Key Program of Natural Science Foundation of Yunnan Province, China （No. 2003C0010Z）.
文摘Objective To investigate the expression of nerve growth factor （NGF） and glial cell line-derived neurotrophic factor （GDNF） in monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. Methods The monkeys were immediately removed brain after death in operation of group A （identical temperature perfusion group） and group B （ultraprofound hypothermia perfusion group）. Immunohistochemical technique was used to determine frontal cellular expression of NGF and GDNF. Statistics were analyzed by ANOVA analyses with significance level at P 〈 0.05. Results The expressions of NGF and GDNF in the group B were significantly higher than those in the group A （P 〈 0.05）. Conclusion NGF and GDNF increased significantly in the monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. It may be a protective mechanism for neuron survival and neural function recovery.
基金Supported by Project of Alternative Resources Prospecting in Crisis Mines(No.200623018)
文摘The Qilishan gold deposit is located in the southern Zhaolai gold ore belt in the northwestern Jiaodong region.A total of seven gold ore bodies have been found in the mining area.Linglong gneissic biotite granite and the NE trending Lingbei fracture control the output and distribution of the gold deposit.The ore bodies with veined or irregular shape occur in the structural alteration zone.The ore bodies of different sizes are NE trending and SE dipping.The constituent minerals of the ores mainly include pyrite,chalcopyrite,native gold,electrum,argentite,matildite,hematite,quartz and calcite.The ores are characterized by metasomatic dissolution structure,as well as veined and brecciated structures.The ore-forming process is divided into four stages,namely quartz-,pyrite-,polymetallic-and carbonate stages.Study on fluid inclusion shows that the deposit is composed of gas-liquid two-phase inclusions （Ⅰ） and three-phase inclusions containing CO2 （Ⅱ）,and that the former dominates.The homogenization temperature is 259.6℃-373.7℃ ; the salinity of three-phase inclusions containing CO2is 5.77%-9.84% （NaCl） ; the salinity of gas-liquid two-phase inclusions is 6.58%-8.54% （NaCl） ; and the estimated ore-forming pressure is 55.2-82.2 MPa.According to the nonlinear relationship between the depth and pressure of the fluid in the fracture zone,the ore-forming depth of the Qilishan gold deposit is calculated as 5.95-7.14 km.It is preliminarily determined that the deposit is a mesophilic and hypothermal gold deposit.
基金Supported by National Science and Technology Major Project,No.2012ZX10002-017Natural Science Foundation of China for Innovative Research Group,No.81121002+4 种基金National Natural Science Foundation of China,No.81000137 and No.81470891The Qianjiang Talent Program of Zhejiang Province,China,No.2012R10045the Scientific Research Program for the Returned Overseas Chinese Scholars,Ministry of Health,China,No.J20112008National High Technology Research and Development Program of China for Young Scientists(863 Program),No.2015AA020923Ministry of Education,Zhejiang Province,China,No.Y201328095
文摘AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best(vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001).CONCLUSION: HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP.
基金Project supported by the National Natural Science Foundation of China(No.81871541)。
文摘Oxidative stress and apoptosis are the key factors that limit the hypothermic preservation time of donor hearts to within 4–6 h.The aim of this study was to investigate whether the histone deacetylase 3(HDAC3)inhibitor RmGodFyPn9 a6 m6 i cc opualrda mpreotteercst daugrianing srt ecpaerrdfiuasci oinn juwreyr ei nedvuacleuda tebyd.pTrholeo nexgperde shsyipoont haenrdm pich opsrpehsoerryvlaattiioonn.leRvaet lsh eoaf rtms awmemrea lihayn-??STE20-like kinase-1(Mst1)and Yes-associated protein(YAP)were determined by western blotting.Cell apoptosis was measured by the terminal deoxynucleotidyl-transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)method.Addition of RGFP966 in Celsior solution significantly inhibited cardiac dysfunction induced by hypothermic preservation.RGFP966 inhibited the hypothermic preservation-induced increase of the phosphorylated(p)-Mst1/Mst1 and p-YAP/YAP ratios,prevented a reduction in total YAP protein expression,and increased the nuclear YAP protein level.Verteporfin(VP),a small molecular inhibitor of YAP–transcriptional enhanced associate domain(TEAD)interaction,partially abolished the protective effect of RGFP966 on cardiac function,and reduced lactate dehydrogenase activity and malondialdehyde content.RGFP966 increased superoxide dismutase,catalase,and glutathione peroxidase gene and protein expression,which was abolished by VP.RGFP966 inhibited hypothermic preservation-induced overexpression of B-cell lymphoma protein 2(Bcl-2)-associated X(Bax)and cleaved caspase-3,increased Bcl-2 mRNA and protein expression,and reduced cardiomyocyte apoptosis.The antioxidant and anti-apoptotic effects of RGFP966 were cancelled by VP.The results suggest that supplementation of Celsior solution with RGFP966 attenuated prolonged hypothermic preservation-induced cardiac dysfunction.The mechanism may involve inhibition of oxidative stress and apoptosis via inactivation of the YAP pathway.
基金supported by the National Natural Science Foundation of China,No.81401084(to XHW)the Beijing Municipal Administration of Hospital Ascent Plan in China,No.DFL20150802(to TLW)+2 种基金the Beijing 215 High Level Healthcare Talent Plan Academic Leader in China,No.008-0027(to TLW)the Beijing Municipal Commission of Health and Family Planning in China,No.PXM2017_026283_000002(to TLW)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support in China,No.ZYLX201706(to TLW),303-01-005-0137-11(to TLW),65683.00(to TLW)
文摘Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulatory arrest are unclear. After piglet models underwent 60 minutes of deep hypothermic circulatory arrest at 14°C, expression of microRNAs(miRNAs) was analyzed in the hippocampus by microarray. Subsequently, TargetScan 6.2, RNA22 v2.0, miRWalk 2.0, and miRanda were used to predict potential targets, and gene ontology enrichment analysis was carried out to identify functional pathways involved. Quantitative reverse transcription-polymerase chain reaction was conducted to verify miRNA changes. Deep hypothermic circulatory arrest altered the expression of 35 miRNAs. Twenty-two miRNAs were significantly downregulated and thirteen miRNAs were significantly upregulated in the hippocampus after deep hypothermic circulatory arrest. Six out of eight targets among the differentially expressed miRNAs were enriched for neuronal projection(cyclin dependent kinase, CDK16 and SLC1 A2), central nervous system development(FOXO3, TYRO3, and SLC1 A2), ion transmembrane transporter activity(ATP2 B2 and SLC1 A2), and interleukin-6 receptor binding(IL6 R)– these are the key functional pathways involved in cerebral protection during deep hypothermic circulatory arrest. Quantitative reverse transcription-polymerase chain reaction confirmed the results of microarray analysis. Our experimental results illustrate a new role for transcriptional regulation in deep hypothermic circulatory arrest, and provide significant insight for the development of miRNAs to treat brain injuries. All procedures were approved by the Animal Care Committee of Xuanwu Hospital, Capital Medical University, China on March 1, 2017(approval No. XW-INI-AD2017-0112).
文摘The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.
基金Supported by the National Natural Science Foundation,No.81470896the Project of Development and Innovation Team of Ministry of Education,No.IRT_16R57
文摘AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion(HMP).METHODS Eighteen young(4 mo old) and 18 aged(17 mo old)healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group(UWP), and UW solution with metformin perfusion group(MUWP). Aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), interleukin-18(IL-18), and tumor necrosis factor-alpha(TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase(e NOS) in liver sinusoidal endothelial cells were also examined.Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done. RESULTS AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively,significantly lower in the MUWP group than in the UWP group(P < 0.05), but no significant differences were found between the young and aged MUWP groups.Metformin increased the expression of AMPK and e NOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-e NOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.CONCLUSION The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.
文摘Acute-on-chronic liver failure(ACLF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term mortality.Partially due to the lack of universal diagnostic criteria,the actual ACLF prevalence remains unclear;nevertheless,it is expected to be a highly prevalent condition worldwide.Earlier transplantation is an effective protective measure for selected ACLF patients.Besides liver transplantation,diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy.Although new clinical specific therapies have been researched,more studies are necessary to assess safety and efficacy.Therefore,future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow.Thus,an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality.In addition,while donor organ quality is meant to be a prognostic factor in the ACLF setting,recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.
文摘The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.
基金funding received in the form of the Catherine Marie Enright research scholarship from the Royal Australasian College of Surgeons to support his program of research
文摘The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.
文摘The technique for bloodless hepatic resection using the total hepatic vascular isolation under the normothermic or hypothermic perfusion was reported to deal with the large liver tumor involving in the liver hilum,the main hepatic veins or the retrohepatic vena cava.The original Heaney's and Fortner's methods were modified so that the technique could be simpler and more practicable to perform otherwise hazardous liver resection.During the past 4 year,major hepatic resection with the normothermic or hypothermic total vascular exclusion technique was successfully performed on 19 patients with liver tumors in our department.Among the 19 cases,16 underwent hepatic resection with the normothermic selective total vascular exclusion(extended right lobectomy in 5 cases,extended left lobectomy in 3 cases;right lobectomy in 5 cases;central segmentectomy in 3 cases)and 3 with the total vascular isolation and in situ cold perfusion(extended left lobectomy in 2 case,extended right lobectong in 1case).We believe that the technique of normothermic vascular exclusion may be indicated to deal with the lesion close to the hepatic veins and the retrohepatic vena cava.However,for more complicated hepatic resection,the hypothermic perfusion technique should be considered to prolong the safety of ischemic tune of the liver.The preliminary experience in the clinical application using the above technique is reported.
文摘This study was undertaken to analyze the perioperative factors and complications that influence the final outcome after deep hypothermic circulatory arrest and superficial hypothermia during operations on aortic aneurysms from Jan 2000 to Jun 2004. The results show that deep hypthermic circulatory arrest group provided a high risk of pulmonary insufficiency-hypoxemia and temporary neurological dysfunction in complication but not increased the risk of hospital mortality.
基金Technology Innovation and Application Development Project of Chongqing,No.2021yc-cxfz30016.
文摘BACKGROUND Persistent left superior vena cava(PLSVC),a relatively rare thoracic vascular malformation,can inconvenience perfusionists and operators when encountered during deep hypothermic circulatory arrest(DHCA).CASE SUMMARY Herein,we describe the case of a patient with concurrent giant aortic arch aneurysm,aortic stenosis,and PLSVC.To treat these conditions,we performed right hemiarch and aortic valve replacements under DHCA.Notably,we applied“bilateral superior vena cava retrograde cerebral perfusion(RCP)”for cerebral protection,which significantly optimized the surgical procedure and reduced the risk of postoperative complications.The patient was discharged 14 d after surgery with no complications.CONCLUSION Surgical intervention for PLSVC under DHCA can be performed using the bilateral superior vena cava RCP approach.
文摘Background: In clinical and basic science medicine, we often isolate ourselves in silos, unaware of developments in other related disciplines. Our team has had substantial experience, both in the operating room and in the laboratory, with protecting the brain and the spinal cord via hypothermia. Herein, we briefly share this experience with our colleagues in Neurology, eager for comments and advice from the neurologic perspective. Methods: 1) Clinical brain protection via deep hypothermic circulatory arrest (DHCA) for surgery of the aortic arch. For aortic arch replacement (performed for aortic arch aneurysm or aortic dissection), the aortic arch must be opened and native perfusion stopped. We have decades of experience in many hundreds of patients with this technique. This experience is reviewed. 2) Experimental protection of the spinal cord via cooling. We review our laboratory experience with a novel, recirculating cooling catheter for the vulnerable spinal cord. 3) Experimental protection of the brain via an intraventricular cooling catheter. We review our laboratory experience cooling the brain with a balloon-tipped catheter residing the lateral ventricles. Results: 1) Deep hypothermic circulatory arrest for aortic arch surgery provides superb brain protection for periods up to 45 minutes or longer. Clinical neurologic function, and quantitative neurologic tests, show excellent brain preservation. 2) The novel spinal cooling catheter provides excellent cooling of the spinal cord in a large animal model, without apparent injury of any type. 3) The intraventricular brain cooling catheter provides excellent cooling of the brain, documented by both direct temperature probe and high-tech brain imaging. Conclusions: We wish herein (in this article) to share this experience across our disciplines (Cardiac Surgery and Neurology). We welcome advice from the Neurology community on these surgically-directed methods for cooling and protection of neurological tissue in both the brain and the spinal cord.
