The Condyloma Acuminatum’s Recurrence Can Be Reduced by Lesional Auto-Transplantation

Background: Condyloma acuminatum (CA), also known as a genital wart (GW), is a sexually transmitted disease caused by human papillomavirus (HPV). HPV lesions, recurrence tendency, and risk of malignant formation are primarily dependent on the person’s immunity level. GW recurrence is a major challenge in CA treatment. The aim of this study was to explore how lesional auto-transplantation (LT) can be used to treat CA and decrease its recurrence. Methods: We treated CA through the preparation and implantation of tissue from nine CA patients in our dermatology clinic. Transplantation of small pieces of HPV lesions to the subcutaneous fat of the inguinal region was carried out with the help of a simple surgical method under local anesthesia. Patients were followed up for six to eight months. We searched PubMed and the Web of Science for treatment options for CA to compare our treatment method recurrence rate with existing treatment options. Results: During three months of follow-up, seven patients experienced no recurrence of condyloma lesions, while two patients experienced recurrence of small lesions of condyloma acuminatum. The recurrence rate of CA once treated by auto-transplantation was relatively low compared to other CA treatment options. Conclusions: Transplantation of HPV lesions to the inguinal area reduces the recurrence rate in sexually active individuals. The 2/9 recurrence after implantation could be due to poor hygiene, sexual relationships or immune factors.

Histomorphological observation in arterial remodeling following New Zealand rabbit auto-extremity artery transplantation

Objective： To investigate the histomorphological change in auto-extremity artery following transplantation. Methods： 50 New Zealand rabbits were randomly divided into 5 groups（postoperative 1 d, 3 d, 7 d, 14 d, 56 d, n = 10）. Femoral artery was harvested and end-to-side anastomosed with carotid in order to build the auto-extremity arterial graft animal model. On the postoperative 1^st, 35^nd, 7^th, 14th and 56^th days, grafts for morphometric analysis under the Image analysis system were obtained; and electron microscope was scanned to observe endothelial cells. In addition, Immunostaining of sections were performed with the mouse monoclonal antibody of the a -smooth muscle isoform of actin and proliferating cell nuclear antigen antibody. Results： Overall patency rate for all conduits was 86%.The intimal hyperplasia was first observed in the 7^th day group, and continued to increase in the 56^th day group（183.21 ± 111.74） μ m, P 〈 0.01. Additionally, the luminal narrowed（32.43 ± 18.28）% in the 56^th day group. Smooth muscle cells were the mainly hyperplastic components. The most active proliferation of cells was detected in the 14^th day group, where the extracellular matrix gradually deposited in the intima. Conclusion： Moderate intimal hyperplasia occurred in arterial conduits and vascular structure experienced constrictive remodeling after auto-transplantation.

Total pancreatectomy and islet autotransplantation: A decade nationwide analysis

AIM: To investigate outcomes and predictors of inhospital morbidity and mortality after total pancreatectomy(TP) and islet autotransplantation. METHODS: The nationwide inpatient sample(NIS) database was used to identify patients who underwent TP and islet autotransplantation(IAT) between 2002-2012 in the United States. Variables of interest were inherent variables of NIS database which included demographic data(age, sex, and race), comorbidities(such as diabetes mellitus, hypertension, and deficiency anemia), and admission type(elective vs nonelective). The primary endpoints were mortality and postoperative complications according to the ICD-9 diagnosis codes which were reported as the second to 25 th diagnosis of patients in the database. Risk adjusted analysis was performed to investigate morbidity predictors. Multivariate regression analysis was used to identify predictors of in-hospital morbidity.RESULTS: We evaluated a total of 923 patients who underwent IAT after pancreatectomy during 2002-2012. Among them, there were 754 patients who had TP + IAT. The most common indication ofsurgery was chronic pancreatitis(86%) followed by acute pancreatitis(12%). The number of patients undergoing TP + IAT annually significantly increased during the 11 years of study from 53 cases in 2002 to 155 cases in 2012. Overall mortality and morbidity of patients were 0% and 57.8 %, respectively. Postsurgical hypoinsulinemia was reported in 42.3% of patients, indicating that 57.7% of patients were insulin independent during hospitalization. Predictors of inhospital morbidity were obesity [adjusted odds ratio(AOR): 3.02, P = 0.01], fluid and electrolyte disorders(AOR: 2.71, P < 0.01), alcohol abuse(AOR: 2.63, P < 0.01), and weight loss(AOR: 2.43, P < 0.01). CONCLUSION: TP + IAT is a safe procedure with no mortality, acceptable morbidity, and achieved high rate of early insulin independence. Obesity is the most significant predictor of in-hospital morbidity.

Transplantation Expression of 4-1BB molecule on peripheral blood T cells in liver transplanted patients and its clinical implication

OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients receiving liver transplantation, 13 patients with primary liver carcinoma (PLC), and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on the surface of CD4^+ and CD8^+ T cell, flow cytometry was used to analyse the phenotype of T cell subsets from the blood of liver transplantation patients. RESULTS: 4-1BB mRNA was detected in PBMCs from stable survivors after liver transplantation, but almost not deteeted in PBMCs from PLC patients and healthy controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4^+ and CD8^+ T cells in healthy controls and PLC patients. A low level of 4-1BB expression, however, was found on the surface of CD4^+ and CD8^+ T cells from the stable survivors after liver transplantation. CONCLUSIONS: This study demonstrates that although patients are stable after liver transplantation, effector T-cells can also be activated through the signal of 4-1BB molecule and persistent irmmune response to grafts. Blockage of 4-1BB/4-1BBL pathway may benefitially reduce the clinical dosage of immunosuppressive agents and prolong the survival of grafts.

Homogeneous phenomenon of the graft when using different genotype characteristic of recipients/donors in living donor liver transplantation

AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3A5*3,MDR1-3435 and CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/donor with different genotype polymorphisms and 119liver graft biopsy samples used with the pyrosequencing technique after LDLT.Polymerase chain reaction/ligase detection reaction assay and restriction fragment length polymorphism was employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide poly-morphisms(SNPs).All of the recipients and donors expressed with the similar SNP genotype of CYP3A5*3,MDR1-3435 or CYP3A4*18 were excluded.RESULTS:The final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3,MDR1-3435 and CYP3A4*18 was predominated depends on the donor with restriction fragment length polymorphism and seems to be less related to the recipient.The proportional changes of G to A alleles of the 119 samples of CYP3A5*3(included A】A/G,A/G】A,A/G】G,G】A,G】A/G and A】G),C to T alleles of the 108 samples of MDR1-3435(included C】C/T,C/T】C,C/T】T,T】C/T and T】C),and T to C alleles of 15 samples of CYP3A4*18(included T/C】T and T】C/T)were significant different between the recipients and the liver graft biopsy samples(P【0.0001)and less difference when compared with the donors in the pyrosequencing analysis after LDLT.CONCLUSION:The CYP3A5*3,MDR1-3435 and CYP3A4*18 of the recipient could be modified by the donor so-called homogenous phenomenon when the recipient’s blood drained into the liver graft.

BUILDING OF A SIMPLE MODEL OF AUTO-OLT IN DOGS AND ITS SIGNIFICANCE

AIM: we recommend a method of Simple auto-oLT model in dogs.METHODS:The model was ligated all ligaments or connective tissues of the liver,only reserved the vascular construction,that was the suprahepatic and infrahepatic inferior vena cava,portal vein,hepatic artery or common bile duct.the operation was similar to the orthotopic liver transplantation except vascular anastomoses,the dog liver underwent the warm or cold ischemia and the reperfusated injurous process.RESULTS: The imitability was exactly good and the operation was simple and safe. Because the hepatic vessels of the going out or coming in was clamped block and might open or blind the blood flow whenever necessary,the model might control the warm or cold ischemic time accurately,and eliminate the influence or the complications due to vascular anastomoses.CONCLUSIONS: The model avoided many-sided Influences of the traditional OLT and was a good method to study hepatic artery or portal vein ischemic injury and created a new way to explore the pathogenesis or some complications in the OLT.

Investigation on the Structure of Chute-feed and Card Auto-leveller and Their Selection of Technological Processes

Based on the structure of chute - feed and autoleveHer, an analysis of their working principle and the verification of their practical production results have been carried out. Finally, the future investigation direetiom of chute - feed and card autuleveller are put forward.

椭圆-不完全非圆齿轮行星系取苗机构参数优化

针对椭圆-不完全非圆齿轮行星系蔬菜钵苗取苗机构的参数优化是具有非线性、模糊性、强耦合性的多目标复杂优化问题,建立了该机构的运动学模型及优化目标函数,运用参数导引优化方法,通过Visual Basic可视化平台开发了取苗机构运动学优化软件。应用该优化软件可方便地获得的一组机构参数,通过虚拟仿真可以看出所优化的参数能够满足取苗工作轨迹要求。试验样机进行了取苗试验,验证了取苗机构参数的合理性和有效性。

自动固相微萃取(SPM E)GC-MS、GC-MS-MS法检测环境水中有机磷杀虫剂的研究

固相微萃取(solid-phase microextraction,SPME)是20世纪90年代发展起来的一种样品前处理技术,与传统的液-液提取、液-固提取相比,SPME更适用于提取、浓缩液态或气态的挥发性和半挥发性物质,SPME技术可将采样、萃取、浓缩和样本引入集中于一个步骤完成,尤其随着自动SPME与GC-MS等联用技术的日益完善,使SPME技术优点得到更充分的发挥.……

急性髓细胞白血病患者DC-CIK治疗后T细胞亚群动态变化的临床观察

目的观察急性髓细胞白血病患者经自体外周血移植联合自身白血病细胞冻融抗原负载的DC-CIK输注治疗后体内的T细胞亚群动态变化。方法选择50名初发急性髓细胞白血病患者,抽取其未缓解的骨髓制备自身白血病细胞冻融抗原,在自体外周血干细胞采集时分离部分单个核细胞培养DC-CIK,以自身白血病冻融抗原共培养激活扩增DC-CIK。患者自体外周血造血干细胞移植30～60 d输注自身白血病细胞冻融抗原负载的DC-CIK,每例每疗程回输细胞总数>7×109,同时给予IL-2(20 WU皮下注射,1次/d,连续10 d)皮下注射。动态观察患者接受DC-CIK细胞输注治疗后不同时间点体内T细胞亚群动态变化,并与既往接受自体外周血移植但未输注DC-CIK细胞治疗的52名急性髓细胞白血病患者进行比较分析。结果 50名患者DC-CIK输注后患者体内CD8+、CD16+、CD56+淋巴细胞均显著高于输注治疗前水平(P<0.01),治疗组同一随访时间段CD3+、CD4+、CD8+、CD16+、CD56+淋巴细胞均显著高于未采用DC-CIK治疗组(P<0.01)。结论对急性髓细胞白血病患者采用自体外周血移植联合自身白血病细胞冻融抗原负载的DC-CIK输注治疗,能显著提高患者肿瘤杀伤性T细胞水平,有助于清除移植后微小残留病,改善患者无病生存率(PFS)。

^(99m)Tc-MIBI SPECT-CT在持续性甲状旁腺功能亢进患者手术治疗中的作用

目的比较甲状旁腺99mTc-MIBI SPECT/CT显像与超声检查在持续性甲状旁腺功能亢进患者再次手术治疗中的作用。方法 8例持续性甲状旁腺功能亢进患者,评价患者再次术前超声及99mTc-MIBI SPECT-CT显像在诊断和定位中的敏感性和准确性。结果 8例持续性甲状旁腺功能亢进患者共切除共切除14处组织,甲状旁腺增生结节9枚,其余5处未见增生的甲状旁腺组织。99mTc-MIBI SPECT-CT显像诊断敏感性为100%,准确性为78.6%;而超声诊断敏感性为77.8%,准确性为50%。统计学分析显示二者之间有显著性差异(P=0.021),99mTc-MIBI SPECT-CT显像与超声检查发现的甲状腺上、下极甲状旁腺的数目一致,但99mTc-MIBI SPECT-CT显像比超声检查多发现2枚异位甲状旁腺结节,二者之间无明显统计学意义(P=0.300)。99mTc-MIBI SPECT-CT检查发现的另两例异位于食管旁沟、升主动脉旁的结节结节虽然未能取得病理结果,但随后随访中这2例患者的i PTH分别为800、1429pg/ml,远远高于其余4位患者的i PTH(<400)pg/ml。结论再次甲状旁腺全切术是治疗持续性甲状旁腺功能亢进的一种安全和有效的手段,与超声检查比较,99mTc-MIBI SPECT/CT显像通过病灶摄取99mTc-MIBI及与CT结合从而对功能增强的甲状旁腺组织准确定位,并能发现纵隔内异位甲状旁腺组织,能为持续性甲状旁腺功能亢进术前定位提供更多帮助。

RT-PCR方法对检测乳腺癌干细胞富集血残存肿瘤细胞的价值

目的：旨在用敏感的ＲＴ－ ＰＣＲ 方法扩增目的基因，用于检测干细胞富集血中残存的肿瘤细胞。方法：应用ＲＴ－ ＰＣＲ 方法检测样品ＭＵＣ１ 、Ｋ１９ 基因的表达情况。结果：乳腺癌细胞系ＭＣＦ－ ７ 中ＭＵＣ１ 、Ｋ１９ 表达阳性，而在淋巴细胞中则未见有表达。进一步用淋巴细胞稀释乳腺癌细胞来检测该方法的灵敏度。ＭＵＣ１ 、Ｋ１９ 检测残存肿瘤细胞的灵敏度均达到１／１０５ 。在此基础上，完成了１５ 例乳腺癌患者干细胞富集血检测工作。结论：ＲＴ－ ＰＣＲ 是检测残存肿瘤细胞检测中行之有效的方法。

3种G-CSF动员224例外周血干细胞效果比较

目的比较3种粒细胞集落刺激因子(G-CSF)对外周血干细胞的动员效果。方法我科自体外周血干细胞移植病人224例,采用3种粒细胞集落刺激因子(吉赛欣、欣粒生、惠尔血)进行外周血干细胞动员,对干细胞动员情况、干细胞质量、移植后造血重建和药物毒副作用进行比较。结果224例病人全部移植成功,其动员效果、干细胞质量及在移植后造血重建中的临床效果差异均无显著性,毒副作用小。结论吉赛欣和欣粒生两种国产制剂及惠尔血能可靠用于外周血干细胞动员及造血重建,尤其是国产制剂的价格明显低于进口产品,在有效保证动员效果的同时大大减轻了病员的经济负担,值得临床应用推广。

A 26-year clinical observation of splenic auto-transplantation and oesophageal transection anastomosis:a new treatment strategy in patients with portal hypertension

Background Surgical treatment options for patients with cirrhosis and portal hypertension are complicated. In this study we evaluated the effectiveness of a new treatment strategy, splenic auto-transplantation and oesophageal transection anastomosis. We report results from clinical observations, splenic immune function and portal dynamics in 274 patients. Methods From 1979 to 2005, 274 cirrhosis patients with portal hypertension underwent the new treatment strategy, and were followed up to compare results with those patients who underwent traditional surgical treatment. From 1999 to 2002 a randomized controlled trial （RCT） was performed on 40 patients to compare their post-operative immune function. From 1994 to 2006, another RCT enrolled 28 patients to compare portal dynamics using three-dimensional dynamic contrast-enhanced magnetic resonance angiography （3D DEC MRA） investigation post operation. Results Among 274 patients （mean age 41.8 years）, the emergency operative mortality （4.4%）, selective operative mortality （2.2%）, complication rate （17.9%）, prevalence of hepatic encephalopathy （〈1%）, rate of portal hypertension gastritis （PHG） bleeding （9.1%）, and morbidity of hepatic carcinoma （8%） were similar to those patients undergoing traditional operation; the spleen immunology function （Tuftsin, IgM） decreased in both groups 2 months post operation, but this decrease did not reach statistical significance. Through 3D DCE MRA, the cross sectional area and the velocity and volume of blood flow of the main portal vein decreased significantly after operation in both groups. The velocity and volume of blood flow in the auto-transplantation group was significantly lower than that in the control group. Conclusions Splenic auto-transplantation and esophageal transection anastomosis is a safe, effective, and reasonable treatment strategy for patients with portal hypertension with varicial bleeding. It not only can correct hypersplenism, but may also achieve complete hemostasis. Spleens auto-transplanted into the retroperitoneal space can preserve immune function and establish broad collateral circulation.

CTLA-4Ig治疗作用的实验研究进展

控制器官移植后的排斥反应以及治疗风湿性关节炎之类的自身免疫性疾病一直是医学科学领域的难题。传统采用一些非特异的免疫抑制剂比如激素、环孢霉素进行治疗 ,其作用有限 ,而且会导致全身感染、肿瘤发生等副作用。CTLA 4Ig是人CTLA 4分子胞外区与人免疫球蛋白γ1绞链区、CH2、CH3区组成的融合蛋白 ,与B7有高度的亲和力 ,可以阻断B7与CD2 8的结合。它不但可以封闭B7,导致免疫耐受 ,而且可以调节免疫细胞的分化 ,调节免疫反应。因而 ,作为一种人类基因工程生物制剂 ,它在抗移植排斥反应、治疗自身免疫性疾病等方面具有重要的应用价值 。

Primary cutaneous anaplastic large cell lymphoma with overexpressed Ki-67 transitioning into systemic anaplastic large cell lymphoma:A case report

BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)differs from systemic anaplastic large cell lymphoma(sALCL)in cell biological behavior,clinical features,treatment,and outcome.PC-ALCL has been reported to rarely transition into sALCL,but the underlying mechanism is not clear.Here we report such a case with certain characteristics that shed light on this.CASE SUMMARY Herein,we report a 43-year-old male with symptoms of a skin nodule and histologically confirmed PC-ALCL with high expression of Ki-67.After three months of observation,two skin nodules re-appeared with muscle layer involvement and was histologically confirmed as sALCL.Seventeen months after receiving six cycles of CHOP regimen,the patient had pain in the chest and back,cough,shortness of breath,and night sweats.This was confirmed as relapse of sALCL by immunohistochemistry and several organs,such as the lung were involved as shown by positron emission tomography/computed tomography.After four cycles of DICE plus chidamide regimens followed by auto-hematopoietic stem cell transplantation(ASCT),complete remission(CR)duration was achieved for twelve months while the patient was on maintenance with chidamide(20 mg)pills.CONCLUSION This case had significantly high expression of Ki-67 when diagnosed as PC-ALCL initially and then transitioned into sALCL,which is rare.Auto-ASCT combined with demethylation drugs effectively maintained CR and prolonged progression free survival.

Utility of the low-accelerating-dose regimen in 182 liver recipients with recurrent hepatitis C virus

AIM: To describe our experience using a low-acceleratingdose regimen(LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis C virus(HCV) recurrence. METHODS: From 2003, a protocolized LADR strategy was employed to treat liver transplant(LT) recipients with recurrent HCV at our institution. Medical records of 182 adult patients with recurrent HCV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28 B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B(rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include(1) patient and graft survival;(2) effect of anti-viral therapy on liver histology(fibrosis and inflammation);(3) incidence of on-treatment development of ACR, CDR, or PCH;(4) association of recipient and donor IL28 B genotype with SVR; and(5) incidence of antiviral therapy-associated adverse events(anemia, leukopenia, thrombocytopenia, depression) and hepatic decompensation.RESULTS: The overall SVR rate was 38%(29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HCV Gt(P < 0.0001), donor age(P = 0.003), cytomegalovirus mismatch(P = 0.001), baseline serum bilirubin(P = 0.002), and baseline viral load(P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-CC/donor-non CC pairs(P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR(97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L(P = 0.01), total bilirubin ≥ 1.5 mg/d L(P = 0.001) and creatinine ≥ 2 mg/d L(P = 0.001) were independently associated with patient survival. Only 13% of patients achieving SVR died during the followup period. Treatment discontinuation and treatmentrelated mortality occurred in 35% and 2.2% of patients, respectively. EPO, G-CSF and blood transfusion were needed in 89%, 40% and 23% of patients, respectively. Overall hospitalization rate for treatment-related serious adverse events was 21%. Forty-six(25%) of the patients were deceased; among those who died, 25(54%) were due to liver-related complications, and 4 deaths(9%) occurred while receiving therapy(2 patients experienced hepatic decompensation and 2 sepsis). CONCLUSION: LADR strategy remains relevant in managing post-LT recurrent HCV where access to DAAs is limited. SVR is associated with improved survival, but fibrosis progression still occurs.

两种rhG-CSF制剂用于自体外周造血干细胞移植的效果比较

目的探讨两种重组人粒细胞集落刺激因子吉赛欣(国产rhG-CSF)和惠尔血(进口rhG-CSF)在外周造血干细胞(PBSC)动员及移植后造血恢复中的效能差异。方法选择2000-01～2003-05在本院进行自体外周造血干细胞动员的47例血液肿瘤患者,随机分为两组,在化疗后白细胞降至最低点时分别接受国产rhG-CSF和进口rhG-CSF进行干细胞动员,比较rhG-CSF使用时间及采集所得CD34+细胞数量,其中接受干细胞回输的41例再随机分组,在预处理和干细胞回输后,外周WBC达到0×109/L时分别接受两种rhG-CSF促进造血恢复,比较外周血中性粒细胞绝对计数(ANC)恢复至≥1.5×109/L的天数及rhG-CSF使用时间。结果47例进行干细胞动员的患者中,24例应用进口rhG-CSF,23例应用国产rhG-CS,使用时间分别为6.17±2.64d和5.78±1.83d,所得采集物CD34+细胞总数分别为(5.90±5.06)×106/kg体重和(5.13±6.07)×106/kg体重,两者比较无显著性差异。41例接受自体干细胞回输的患者,22例应用进口rhG-CSF,19例应用国产rhG-CSF,使用时间分别为10.86±2.41d和10.83±4.75d,ANC恢复至≥1.5×109/L的时间分别为9.07±1.50d和10.00±4.20d,两者比较亦无显著性差异。结论两种rhG-CSF制剂在PBSC动员、PBSC回输后造血恢复等方面无明显差异,均可供临床上选择使用。

Blockade of 4-1BB/4-1BB ligand interactions prevents acute rejection in rat liver transplantation

Background Blocking the 4-1BB/4-1BB ligand （4-1BBL） signal may modulate the secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play a key role in organ transplantation tolerance. The aim of this study was to investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody （mAB） in acute rejection of rat orthotopic liver transplantation. Methods The orthotopic liver transplantation model was set up, while male Lewis rats were used as liver donors and Brown-Norway rats as recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB or isotype control antibody. Groups were monitored for graft survival after transplantation. Plasma chemistry, including aspartate transaminase （AST）, alanine aminotransferase （ALT）, and bilirubin （BIL）, was assayed. The concentrations of interleukin （IL）-2, IL-10 and interferon （IFN）-γ in plasma were also measured by enzyme-linked immunosorbent assay. Allograft histology images were collected under light microscope and electron microscope. Results Isotype antibody treated recipients exhibited elevated plasma levels of liver injury markers including AST, ALT and BIL, progressive portal and venous inflammation and cellular infiltration of the liver ailografts, and a mean graft survival time （MST） of 10.9 days. Administration of anti 4-1BBL mAB resulted in a decrease in plasma levels of liver injury markers and the concentrations of IL-2, IL-10 and IFN-γ. The histological grade of rejection on day 7 decreased and MST （17.3 days） increased substantially. Conclusions These results demonstrate that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a promising strategy to prevent progression of graft rejection by suppressing T cell-mediated immunity.

Validation of novel Japanese indication criteria and biomarkers among living donor liver transplantation recipients with hepatocellular carcinoma - a single center retrospective study

Aim:To validate a novel Japanese indication criteria for liver transplantation(LT)for hepatocellular carcinoma(HCC),i.e.,the 5-5-500 criteria(nodule size≤5 cm in diameter,nodule number≤5,and alfa-fetoprotein(AFP)value≤500 ng/mL)and the Japanese double eligibility criteria(DEC)(patients meeting the Milan or the 5-5-500 criteria)in the University of Tokyo cohort.The usefulness of biomarkers in predicting the recurrence of HCC was also verified.Methods:The overall survival and recurrence rates of patients meeting the Milan,5-5-500,and the Japanese DEC were compared among 153 patients who underwent living donor LT(LDLT)between 1996 and 2019.A receiver-operating characteristics curve analysis was conducted to evaluate the usefulness of AFP,lens culinaris agglutinin-reactive fraction of AFP,des-gamma-carboxy prothrombin,neutrophil-lymphocyte ratio,and the platelet-lymphocyte ratio to detect recurrence.Results:The 5-year recurrence rate for all patients,those meeting the Japanese DEC,5-5-500 criteria,and the Milan criteria was 10.9%,9.2%,7.4%,and 7.6%,respectively.Compared with the conventional Milan criteria,the 5-5-500 criteria and the Japanese DEC could increase the number of eligible LDLT candidates by 6.1%and 11.4%.Among five biomarkers,the area under the curve value of AFP was the highest(0.852).Conclusion:The results suggest that the 5-5-500 criteria and the Japanese DEC are the appropriate selection criteria for patients with HCC in LDLT.Among five biomarkers investigated,AFP was most reliable to predict HCC recurrence,which justified the utilization of AFP in the 5-5-500 criteria and the Japanese DEC.