How to apply ex-vivo split liver transplantation safely and feasibly: A three-step approach

BACKGROUND Given the current organ shortage crisis,split liver transplantation(SLT)has emerged as a promising alternative for select end-stage liver disease patients.AIM To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT.METHODS A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1,2022,and May 31,2023.The study included 25 SLT cases and 81 whole liver transplantation(WLT)cases.Total ex-vivo liver splitting was employed for SLT graft procurement in three steps.Patient outcomes were determined,including liver function parameters,postoperative complications,and perioperative mortality.Group comparisons for categorical variables were performed using theχ²-test.RESULTS In the study,postoperative complications in the 25 SLT cases included hepatic artery thrombosis(n=1)and pulmonary infections(n=3),with no perioperative mortality.In contrast,among the 81 patients who underwent WLT,complications included perioperative mortality(n=1),postoperative pulmonary infections(n=8),abdominal infection(n=1),hepatic artery thromboses(n=3),portal vein thrombosis(n=1),and intra-abdominal bleeding(n=5).Comparative analysis demonstrated significant differences in alanine aminotransferase(176.0 vs 73.5,P=0.000)and aspartate aminotransferase(AST)(42.0 vs 29.0,P=0.004)at 1 wk postoperatively,and in total bilirubin(11.8 vs 20.8,P=0.003)and AST(41.5 vs 26.0,P=0.014)at 2 wk postoperatively.However,the overall incidence of complications was comparable between the two groups(P>0.05).CONCLUSION Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach,especially under the expertise of an experienced transplant center.The approach developed by our center can serve as a valuable reference for other transplantation centers.

A new veno-venous bypass type for ex-vivo liver resection in dogs

Ex-vivo liver resection is a procedure in which the liver is completely removed, perfused and after bench surgery, the liver is autotransplanted to the original site. Ex vivo liver resection is an important treatment for unresectable liver tumors. This surgical procedure requires long operation time, during which blood flow must be carefully maintained to avoid venous congestion. An effective veno-venous bypass (VVB) may meet this requirement. The present study was to test our new designed VVB device which comprised one heparinized polyvinylchloride tube and three magnetic rings The efficacy of this device was tested in five dogs. A VVB was established in 6-10 minutes. There was no leakage during the procedure. Hemodynamics was stable at anhepatic phase, which indicated that the bypass was successful. This newly-developed VVB device maintained circulation stability during ex-vivo liver resection in our dog model and thus, this VVB device significantly shortened the operation time.

Accuracy of combined PET/CT in image-guided interventions of liver lesions: An ex-vivo study

AIM： Positioning of interventional devices in liver lesions is a challenging task if only CT is available. We investigated the potential benefit of combined PET/CT images for localization of interventional devices in interventional liver studies. METHODS： Thirty lesions each of hyperdense, isodense and hypodense attenuation compared to normal liver parenchyma were injected into 15 ex-vivo pig livers. All lesions were composed of the same amounts of gelatine containing 0.5 MBq of ^18F-FDG. Following lesion insertion, an interventional needle was placed in each lesion under CT-guidance solely. After that, a PET/CT study was performed. The localization of the needle within the lesion was assessed for CT alone and PET/CT and the root mean square （RMS） was calculated. Results were compared with macroscopic measurements after lesion dissection serving as the standard of reference. RESULTS： In hypo- and isodense lesions PET/CT proved more accurate in defining the position of the interventional device when compared with CT alone. The mean RMS for CT and PET/CT differed significantly in isodense and hypodense lesions. No significant difference was found for hyperdense lesions. CONCLUSION： Combined FDG-PET/CT imaging provides more accurate information than CT alone concerning the needle position in FDG-PET positive liver lesions. Therefore combined PET/CT might be potentially beneficial not only for localization of an interventional device, but may also be beneficial for guidance in interventional liver procedures.

Using computed tomography scans to develop an ex-vivo gastric model

The objective of this research was to use abdominal computed tomography (CT) scans to non-invasively quantify anthropometrical data of the human stomach and to concomitantly create an anatomically correct and distensible ex-vivo gastric model. Thirty-three abdominal CT scans of human subjects were obtained and were imported into reconstruction software to generate 3D models of the stomachs. Anthropometrical data such as gastric wall thickness, gastric surface area and gastric volume were subsequently quantified. A representative 3D computer model was exported into a selective laser sintering (SLS) rapid prototyping machine to create an anatomically correct solid gastric model. Subsequently, a replica wax template of the SLS model was created. A negative mould was offset around the wax template such that the offset distance was equivalent to that of the gastric wall thickness. A silicone with similar mechanical properties to the human stomach was poured into the offset. The lost wax manufacturing technique was employed to create a hollow distensible stomach model. 3D computer gastric models were generated from the CT scans. A hollow distensible silicone ex-vivo gastric model with similar compliance to that of the human stomach was created. The anthropometrical data indicated that there is no significant relationship between BMI and gastric surface area or gastric volume. There were inter- and intra-group differences between groups with respect to gastric wall thickness. This study demonstrates that abdominal CT scans can be used to both non-invasively determine gastric anthropometrical data as well as create realistic ex-vivo stomach models.

Mechanical circulatory support in lung transplantation: Cardiopulmonary bypass, extracorporeal life support, and ex-vivo lung perfusion

Lung transplant is the standard of care for patients with end-stage lung disease refractory to medical management. There is currently a critical organ shortage for lung transplantation with only 17% of offered organs being transplanted. Of those patients receiving a lung transplant, up to 25% will develop primary graft dysfunction, which is associated with an 8-fold increase in 30-d mortality. There are numerous mechanical lung assistance modalities that may be employed to help combat these challenges. We will discuss the use of mechanical lung assistance during lung transplantation, as a bridge to transplant, as a treatment for primary graft dysfunction, and finally as a means to remodel and evaluate organs deemed unsuitable for transplant, thus increasing the donor pool, improving survival to transplant, and improving overall patient survival.

Normothermic Ex-vivo Liver Perfusion and the Clinical Implications for Liver Transplantation

Despite significant improvements in outcomes after liver trans-plantation,many patients continue to die on the waiting list,while awaiting an available organ for transplantation.Organ shortage is not only due to an inadequate number of available organs,but also the inability to adequately assess and evaluate these organs prior to transplantation.Over the last few decades,ex-vivo perfusion of the liver has emerged as a useful technique for both improved organ preservation and assessment of organs prior to transplantation.Large animal studies have shown the superiority of ex-vivo perfusion over cold static storage.However,these studies have not,necessa-rily,been translatable to human livers.Small animal studies have been essential in understanding and improving this tech-nology.Similarly,these results have yet to be translated into clinical use.A few Phase 1 clinical trials have shown promise and confirmed the viability of this technology.However,more robust studies are needed before ex-vivo liver perfusion can be widely accepted as the new clinical standard of organ preser-vation.Here,we aimed to review al relevant large and smal animal research,as well as human liver studies on normother-mic ex-vivo perfusion,and to identify areas of deficiency and opportunities for future research endeavors.

Review of ex-vivo characterisation of corneal biomechanics

The evaluation of the corneal biomechanical behaviour has important clinical applications.To name a few,the accuracy of the intraocular pressure measurement,the study of corneal ectatic diseases and the assessment and optimisation of corneal surgical procedures are all highly influenced by corneal biomechanics.Over the last 45 years different ex-vivo methods were developed to study corneal biomechanical behaviour.Different tissue maintenance,support,loading systems,as well as different monitoring strategies of corneal deformations were employed.In this review,the most important and commonly used methods are outlined,including strip extensiometry,inflation,compression,indentation and tissue separation testing.Their particularities,applications,pros and cons and main applications are discussed.

Insight into the history and trends of liver transplantation for echinococcosis:A bibliometric analysis

BACKGROUND Liver transplantation(LT)has demonstrated favorable efficacy in managing endstage alveolar echinococcosis.Nevertheless,the current research focal points and advancement trends remain ambiguous.AIM To map the research landscape to underscore critical areas of focus,influential studies,and future directions of LT for echinococcosis treatment.METHODS Publications on LT for echinococcosis treatment published between 1900 and 2023 were searched in the Web of Science database and analyzed using bibliometrics.RESULTS A total of 14 countries/regions,75 institutions,and 499 authors have published research articles,with China,Turkey,and France being the three most productive countries.The four institutions with the most contributions were Sichuan University,Xinjiang Medical University,the University de Franche Comte,and Inonu University.The three authors who contributed the most were Wen Hao,Wang Wentao,and Bresson Hadni Solange.The four most common keywords were alveolar echinococcosis,LT,ex-vivo liver resection and autotransplantation,and echinococcosis multilocularies.CONCLUSION Our study found that the treatment of complications after LT for echinococcosis treatment and the preoperative surgical plan based on the anatomical relationship between the lesion and the blood vessel are early research hotspots.Recent research focuses on the treatment of complications after ex-vivo liver resection and autotransplantation,especially vascular complications.

Micro-Computed Tomography Applications in Dentistry

Micro-computed tomography (MCT) encompasses two primary scanning options: ex-vivo and in-vivo imaging. Ex-vivo scanning involves the examination of extracted teeth or dental specimens, allowing for detailed analyses of the microarchitecture of mineralized tissue. By analyzing the microarchitecture of dental tissues, MCT can provide valuable information about bone density, porosity, and microstructural changes, contributing to a better understanding of disease progression and treatment outcomes. Moreover, MCT facilitates the quantification of dental parameters, such as bone volume, trabecular thickness, and connectivity density, which are crucial for evaluating the efficacy of dental interventions. This present study aims to comprehensively review and explore the applications of MCT in dentistry and highlight its potential in advancing research and clinical practice. The results depicted that the quantitative approach of MCT enhances the precision and reliability of dental research. Researchers and clinicians can make evidence-based decisions regarding treatment strategies and patient management, relying on quantifiable data provided by MCT. The applications of MCT in dentistry extend beyond research, with potential clinical implications in fields such as dental implantology and endodontics. MCT is expected to play an increasingly significant role in enhancing our understanding of dental pathologies, improving treatment outcomes, and ultimately, benefiting patient care in the field of dentistry.

终末期肝泡型包虫病的肝移植治疗

肝泡型包虫病(HAE)是我国西部地区常见的人畜共患地方性寄生虫病,早期缺乏典型临床表现,症状明显时常已进入终末期,具有极高的致死率。在终末期HAE(es-HAE)治疗中,因残余肝体积不足、无法控制的出血、脉管在体重建困难等,同种异体原位肝移植几乎成为唯一根治的方式。但因供肝短缺、术后需长期使用免疫抑制药等因素限制了其应用,离体肝切除联合自体肝移植术(ELRA)的出现打破了这一窘境,极大拓宽了es-HAE手术指征。此外,我国多中心对ELRA进行了诸多优化与改良,进一步完善es-HAE的治疗体系。目前,es-HAE的肝移植(包括ELRA)治疗仍是临床医师研究的热点。本文对原位肝移植、ELRA、辅助性ELRA等多种手段在es-HAE的外科治疗进行综述,旨在进一步提升es-HAE的诊治水平,改善患者临床预后。

离体肝切除和自体肝移植术的手术研究进展

离体肝切除和自体肝移植术(ex-vivo liver resection and autotransplantation,ELRA)是肝脏外科中的一种复杂术式。ELRA适合于侵犯下腔静脉、门静脉与肝静脉及它们分支的复杂病灶的切除。近几年,经过众多学者对ELRA进行大量的手术实践与研究分析后,ELRA迅速发展。在疾病的适应证中,ELRA着重于晚期肝恶性肿瘤与终末期肝泡型棘球蚴病的治疗。最新的研究中,肝脏Child-Pugh评分B级和残余肝脏体积与标准肝脏体积之比为0.35~0.40的病人也能满足ELRA的肝脏要求。另外,体内临时的门腔静脉分流技术也因其术后死亡率低于过去的体外静脉-静脉转流技术而成为术中首选。术中的血管重建,重点围绕肝后下腔静脉重建方式的选择。对于需重建肝后下腔静脉的病人,则根据病灶切除后肝后下腔静脉壁缺损的程度,采用直接缝合、使用补片、使用人工血管的方式进行重建。现结合文献,对上述领域进行综述。

1470 nm半导体激光对离体动物组织的汽化消融、切割和凝固作用

目的观察1470 nm波长的半导体激光对离体动物组织的汽化切割、凝固和热损伤情况,以探讨其应用于前列腺增生治疗的可行性。方法实验组和同类对照组分别使用HANS-D1型和ML-DD01FI型1470 nm半导体激光治疗仪。取新鲜离体猪膀胱组织,光纤距离组织0.5 cm和1 cm的条件下工作5 s,观察60、90、120、150、160 W功率的半导体激光对组织的损伤影响;取离体犬前列腺和猪肾组织分别进行汽化消融和汽化切割,观察60、90、120、150、160 W功率的半导体激光对组织的汽化和热损伤作用;另在凝结模式下照射离体猪肾组织5、10、15 s后,观察30、40、50 W功率的半导体激光对组织的凝固作用。结果光纤照射距离组织1 cm时,1470 nm半导体激光对邻近正常膀胱组织不会产生意外损伤;但在距离0.5 cm时,120、150、160 W的1470 nm半导体激光对膀胱组织有轻微的损伤。另外,随着输出功率的增大,60~160 W半导体激光对犬前列腺组织的汽化消融效率逐渐提高,且汽化量和消耗总能量之间呈良好的线性相关(P<0.001)。病理组织学HE染色结果显示实验组的凝固层厚度为292.20~309.98μm,汽化层深度为1.49~4.52 mm;同类对照组的凝固层厚度为289.91~303.53μm,汽化层深度为1.88~4.43 mm,两组间比较均未见明显差异(P>0.05)。同时,汽化切割截面积为1 cm2的离体猪肾组织时,60~160 W的1470 nm半导体激光对肾组织的汽化切割效率随输出功率的增大而提高(P<0.05),其中实验组的凝固层厚度为496.04~514.47μm,同类对照组的凝固层厚度为489.39~518.53μm。此外,凝结模式下30、40、50 W的半导体激光对离体猪肾组织照射5、10、15 s时,随着激光输出功率的增加,凝固瘢直径、凹槽深度和凝固效率均逐渐增大(P<0.05);其中实验组和同类对照组的凝固层厚度分别为399.10~449.98μm和392.97~447.65μm,汽化层深度分别为3.05~7.09 mm和2.70~7.14 mm,两组间比较均未见明显差异(P>0.05)。结论1470 nm半导体激光对离体动物组织具有良好的汽化消融、切割和凝固作用,其效果与输出能量之间具有良好的线性相关。

肾脏离体机械灌注治疗新进展

肾移植仍然是终末期肾病病人的金标准治疗方法。为了满足不断增长的器官需求,越来越多地使用心脏死亡捐献者(DCD)或扩大标准捐赠者(ECD)的器官。这些边缘器官发生严重缺血再灌注损伤的风险高,移植后原发性无功能、移植物功能延迟恢复和远期移植物存活率降低的发生率增加。肾脏离体机械灌注(EVMP)与传统静态冷保存相比,可以更好地保护供肾。EVMP还可以作为动态应用药物或基因治疗的平台,以进一步改善肾脏移植疗效。本综述概述了目前EVMP治疗的新策略,包括间充质干细胞疗法、基因疗法、纳米技术、抗感染剂、气体治疗、溶栓药、血型转化等。

高尿酸环境对晶状体透明度的影响及作用机制

目的通过构建大鼠晶状体离体培养模型探讨高尿酸环境对白内障形成的影响及机制。方法采用成年Sprague Dawley大鼠晶状体,在高尿酸培养环境下离体培养。将大鼠晶状体分为空白对照组(15眼)和尿酸干预组(15眼)。尿酸干预组采用含尿酸800μmol·L^(-1)的M-199培养液培养,空白对照组采用不含尿酸的M-199培养液培养,均培养7 d。通过光学显微镜观察两组大鼠晶状体混浊程度;Gomori六胺银法检测两组大鼠晶状体中尿酸盐沉积情况;SA-β-gal染色法检测两组大鼠晶状体细胞衰老情况;TUNEL染色法检测两组大鼠晶状体细胞凋亡情况。结果尿酸干预组大鼠晶状体于第5天时开始出现混浊,并于第7天时混浊分级显著升高,与空白对照组大鼠晶状体混浊分级相比,差异均有统计学意义(均为P<0.05)。空白对照组大鼠晶状体上皮细胞排列整齐,周围未见尿酸盐沉积,仅有极少数蓝染的晶状体上皮细胞,且未发现明显的阳性细胞;尿酸干预组大鼠晶状体赤道部及前囊下晶状体上皮细胞排列紊乱,周围出现黑棕色的尿酸盐结晶,出现较多的蓝染晶状体上皮细胞,且出现了少量阳性细胞。高尿酸环境下,尿酸盐结晶在大鼠晶状体囊膜下沉积,周围晶状体上皮细胞衰老,少量晶状体上皮细胞凋亡。结论高尿酸环境在大鼠晶状体离体培养模型中能够稳定有效地诱导白内障的发生,其机制可能与尿酸诱导晶状体上皮细胞发生衰老和凋亡有关。

人类体外胚胎利用活动的私法回应——以《民法典》第一千零九条为中心

面对人类体外胚胎利用活动,《民法典》不仅选择积极介入而且决定有限开放。为避免潜在风险,《民法典》不仅直接规定了多种风险预防机制,如提高合法标准、设置三大底线和强调人格尊严,而且还间接引致了多种风险预防机制,如划定行为禁区、限制利用对象和实施伦理审查。即便是在《民法典》的框架下,对人类体外胚胎的利用活动所引发的损害进行救济依然是可能的。但是,《民法典》所能供给的侵权责任方案存在很多局限。因此,后续立法应同时引入其他损害救济方案。从我国现行立法来看,潜在选择有强制责任保险方案、商业保险方案、社会救助基金方案和国家补偿方案。后续立法甚至可以建立同时包含四者的综合救济体系。为确保受害人能获得救济,应由国家兜底。

化妆品防腐剂苯氧乙醇和对羟基苯甲酸丙酯的皮肤安全性和暴露量

应用多种试验方法评估苯氧乙醇和对羟基苯甲酸丙酯的皮肤安全性和在皮肤中暴露量。所用的试验方法包括鸡胚绒毛尿囊膜(CAM)、斑马鱼胚模型、细胞中基质金属蛋白酶2(MMP-2)抑制测定法和离体猪皮渗透试验。鸡胚试验显示二者在0.2%质量分数时不会对眼产生刺激性;斑马鱼胚模型表明,2个防腐剂质量分数在0.01%不会对斑马鱼胚摆尾产生显著影响;2个防腐剂质量分数分别为0.1%和0.01%不会对MMP-2产生显著抑制;离体猪皮渗透试验显示对羟基苯甲酸丙酯经皮累积透过量仅是苯氧乙醇累积透过量的5%,但其在皮肤角质层和真皮层中驻留量均较大,在20 min贴敷时约是苯氧乙醇驻留量的2.5和5.8倍。可为化妆品中防腐剂安全使用提供一种评估方法。

在斑点叉尾血清中强力霉素对嗜水气单胞菌药动-药效模型研究

为合理应用强力霉素治疗斑点叉尾(Ictalurus punctatus)细菌性败血症,采用体内药动学和体外药效学相结合的方法,研究了斑点叉尾血清中强力霉素抗嗜水气单胞菌(Aeromonas hydropila)的活性,数据使用3p97和kinetica4.4软件分析。结果表明:强力霉素在普通肉汤培养基和血清中对嗜水气单胞菌的最小抑菌浓度(MIC)均为2.0μg/mL。斑点叉尾按20 mg/kg体重的剂量口灌强力霉素后,药物吸收迅速、达峰快、消除缓慢,血浆药物达峰时间(Tmax)为2.57h,峰浓度(Cmax)为1.72μg/mL,消除半衰期[T(1/2)β]为38.63h。在半效应室内,半效浓度参数(EC50)为16.95h,即血清药物浓度为1.41μg/mL时可产生50%最大效应。PK-PD同步模型参数Cmax/MIC血清为0.86,AUC0→24h/MIC血清为20.57h。通过抑制效应的Sigmoid Emax模型方程可得到临床起到抑菌效果的最佳给药剂量范围为10.68—41.42 mg/kg体重。临床上发生斑点叉尾细菌性败血症时的最佳给药方案建议为:对出现临床病状的斑点叉尾以41.42 mg/kg体重的剂量进行拌饲投喂进行治疗,1次/d。临床上预防斑点叉尾细菌性败血症时以10.68 mg/kg体重的剂量进行拌饲投喂,1次/d。

IL-11基因修饰的基质细胞对造血细胞体外扩增的影响

目的 研究造血因子白介素 11(IL 11)基因修饰的基质细胞对造血细胞体外扩增的影响。方法 采用逆转录病毒载体将IL 11基因转入基质细胞HFCL ,用Northernblot检测基质细胞HFCLIL 11基因的表达 ,用流式细胞仪检测IL 11基因修饰的HFCL支持的脐血CD3 4 + 造血细胞体外扩增中表型为CD3 4 + CD3 8- 早期祖细胞和表型为CD3 4 + CD41+ 巨核系定向祖细胞的比例。结果 基质细胞HFCL能够表达逆转录病毒介导的IL 11基因 ,并且在这种IL 11基因修饰的基质细胞支持下 ,脐血CD3 4 + 造血细胞经过7d扩增 ,扩增细胞中表型为CD3 4 + CD3 8- 的早期祖细胞和表型为CD3 4 + CD41+ 巨核系祖细胞的比例分别为 (1.62± 0 .2 3 ) %、(9.9±1.1) % ,高于未转基因HFCL的 (0 .8± 0 .2 3 ) %、(6.5± 1.8) % ,而在相同条件下细胞因子支持的扩增细胞中则分别为 (0 .19±0 .14 ) %、(6.0± 1.1) %。结论 基质细胞能够表达经逆转录病毒载体介导的IL 11基因 ,而且经IL 11基因修饰的基质细胞能显著促进CD3 4 + CD3 8- 的早期祖细胞和CD3 4 + CD41+ 巨核系祖细胞扩增。

猪半体内氟苯尼考对大肠杆菌的药动学-药效学同步关系研究

采用体内药动学和体外药效学联合的方法,研究氟苯尼考在猪半体内抗大肠杆菌的活性,为合理应用氟苯尼考治疗猪大肠杆菌病提供参考。氟苯尼考在MH肉汤及血清中对猪大肠杆菌的最小抑菌浓度(MIC)分别为3.25和8.75μg.mL-1。猪按20 mg.kg-1的剂量肌内注射氟苯尼考后,药物吸收缓慢且不规则,血浆药物达峰时间为(3.60±1.52)h,峰浓度为(5.28±1.48)μg.mL-1。氟苯尼考在猪体内消除缓慢,体内平均滞留时间为(26.61±9.81)h,消除半衰期为(17.49±8.04)h。半效浓度参数(EC50)为(7.76±4.53)h。AUC0→24h/MIC为(7.69±1.48)h,Cmax/MIC为(0.60±0.17)。由于大肠杆菌对氟苯尼考的敏感性较差和氟苯尼考肌内注射药动学特征的限制,应用氟苯尼考,按照常规方案治疗猪大肠杆菌病,可能导致治疗失败。

丹参酮Ⅱ-A抑制血管合成醛固酮及醛固酮合酶基因CYP11B2信使核糖核酸表达

目的：说明丹参酮ⅡＡ对血管合成血管紧张素Ⅱ及醛固酮的作用。方法：用大鼠肠系膜动脉离体灌注、高效液相色谱法和放射免疫法检测肠系膜动脉中合成的血管紧张素Ⅱ及醛固酮。用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）及ＳｏｕｔｈｅｒｎＢｌｏｔ法检测血管中醛固酮合酶基因ＣＹＰ１１Ｂ２信使核糖核酸（ｍＲＮＡ）的表达情况。结果：丹参酮ⅡＡ抑制血管合成醛固酮，但不能抑制血管合成血管紧张素Ⅱ。丹参酮ⅡＡ抑制血管中醛固酮合酶基因ＣＹＰ１１Ｂ２ｍＲＮＡ的表达。结论：丹参酮ⅡＡ治疗心血管疾病的机制可能与其抑制血管合成醛固酮有关。