器官移植

Abstract:
Objective To analyze the application effect of non-penetrating vascular closure system in portal vein reconstruction of allogenic liver transplantation in adults. Methods Clinical data of 222 patients undergoing allogeneic liver transplantation were retrospectively analyzed. According to whether vascular closure system was used in portal vein reconstruction during operation, all patients were divided into vascular clip group (n=137) and traditional suture group (n=85). Perioperative conditions, clinical prognosis and complications were statistically compared between two groups. Results All patients successfully completed the surgery. The success rate of one-time portal vein anastomosis was 93.4% (128/137) in the vascular clip group. A total of 14 patients died during perioperative period in this study with a mortality rate of 6.3% (14/222). No portal vein-related complications occurred during perioperative period in both groups. The time of portal vein anastomosis in the vascular clip group was (5.6±1.7) min, which was significantly shorter than (10.7±3.6) min in the traditional suture group (P < 0.05). The incidence and grade of perioperative complications did not significantly differ between two groups (all P > 0.05). Conclusions It is safe and feasible to utilize vascular closure system to reconstruct the portal vein during liver transplantation. Compared with traditional suture, it can effectively shorten the time of portal vein anastomosis.

Clinical efficacy of ABO-incompatible living donor liver transplantation: a Meta analysis

Liu Qiang, Luo Fangbiao, Yan Xiong, Luo Shiqiao, Du Chengyou

2018, 9(4): 261-267. doi: 10.3969/j.issn.1674-7445.2018.04.004

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Abstract:
Objective To systematically evaluate the clinical efficacy of ABO-incompatible living donor liver transplantation (ABO-I LDLT) and compare with ABO-compatible LDLT (ABO-C LDLT). Methods A systematic search of multiple databases at home and abroad was conducted to retrieve the literatures related to the statistical comparison of clinical efficacy between ABO-I LDLT and ABO-C LDLT. The literature screening was conducted, the quality of literatures was evaluated and data extraction was performed. Using Rev Man 5.3 software, a Meta-analysis was performed by random effect model or fixed effect model. Results A total of 432 articles were searched, and 6 articles published in English were eventually included according to the inclusion criteria. The Meta-analysis demonstrated that there was no significant difference in the postoperative 1-, 3- and 5-year survival rate of the recipients and grafts and the incidence of rejection responses between the ABO-I LDLT and ABO-C LDLT groups (all P≥0.05). The incidence of postoperative biliary complications and hepatic artery embolization in the ABO-I LDLT group was significantly higher than that in the ABO-C LDLT group [odds ratio (OR) =2.08, 95% confidence interval (CI) 1.25-3.45, P=0.005; OR=2.24, 95%CI 1.03-4.89, P=0.04]. Conclusions Compared with the ABO-C LDLT, ABO-I LDLT yields lower clinical efficacy, whereas it is still an effective method for the treatment of end-stage liver disease.

Long-term survival of bilateral lung transplantation combined with Nuss operation on treatment of bronchiolitis obliterans syndrome complicated with thoracic deformity after hematopoietic stem cell transplantation: report of one case

Ding Hao, Mao Wenjun, Liu Feng, Fan Li, Chen Jingyu

2018, 9(4): 268-271, 277. doi: 10.3969/j.issn.1674-7445.2018.04.005

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Abstract:
Objective To evaluate the clinical efficacy of bilateral lung transplantation combined with Nuss operation on the treatment of bronchiolitis obliterans syndrome (BOS) complicated with pectus excavatum after hematopoietic stem cell transplantation. Methods On March 24, 2015, one patient presenting with BOS complicated with pectus excavatum after hematopoietic stem cell transplantation underwent extracorporeal membrane oxygenation (ECMO)-assisted bilateral lung transplantation in the Department of Thoracic Surgery and Lung Transplantation Center of Wuxi People' s Hospital affiliated to Nanjing Medical University. Simutaneously, Nuss operation was successfully performed to treat pectus excavatum. After anti-inflammation and anti-fungal treatment, a triple immunosuppressive regimen consisting of tacrolimus + mycophenolate mofetil + adrenocortical hormone was implemented. Results The patient was properly recovered and discharged on 25 d after operation. The Nuss steel plate was removed from the chest at postoperative 2 years. The thoracic deformity was corrected. The patient received long-term postoperative follow-up. Until submission date, the patient survived for more than 3 years. The lung function was well restored and the quality of life was satisfactory. Conclusions Bilateral lung transplantation combined with Nuss operation is an effective approach in the treatment of end-stage BOS complicated thoracic deformity.

Study on the relationship between anti-inflammatory cytokine IL-35 and delayed renal graft function

Hu Linkun, Chen Cheng, Wang Weizhen, Zhao Xiaojun, Li Feng, Zhang Xuefeng, Pan Hao, Pu Jinxian, Hou Jianquan

2018, 9(4): 272-277. doi: 10.3969/j.issn.1674-7445.2018.04.006

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Abstract:
Objective To investigate the relationship between the interleukin (IL)-35 and the recovery of renal graft function. Methods Clinical data of 45 recipients receiving renal transplantation from donation after cardiac death (DCD) were retrospectively analyzed. According to the presence of delayed graft function (DGF) after renal transplantation, all recipients were divided into the immediate graft function (IGF) group (n=32) and DGF group (n=13). The serum creatinine (Scr) level and estimated glomerular filtration rate (eGFR) in the recipients were statistically compared between two groups at 1, 2, 3, 7, 14, 28 d and 3, 6 and 12 months after renal transplantation. The IL-35 levels in the serum and urine samples of the recipients were statistically compared between two groups at 1, 2, 3, 7, 14, 28 d following renal transplantation. Results In the DGF group, the renal function was restored slowly. Compared with the IGF group, the Scr level was significantly higher, whereas the eGFR was considerably lower in the DGF group at postoperative 7 d (both P < 0.05). At 1 year after surgery, there was no significant difference in the Scr level between two groups. Compared with the IGF group, the eGFR in the DGF group was significantly lower at postoperative 1 year (P < 0.05). At 1, 2, 3, 7, 14 d after operation, the serum levels of IL-35 in the DGF group were evidently lower than those in the IGF group (all P < 0.05). Compared with the IGF group, the serum level of IL-35 in the DGF group was significantly increased at postoperative 28 d (P < 0.05). At postoperative 1, 2, 3, 7 d, the IL-35 levels in the urine samples in the DGF group were significantly lower than those in the IGF group (all P < 0.05). At postoperative 14 and 28 d, the IL-35 levels in the urine samples did not significantly differ between two groups (both P > 0.05). Conclusions The low levels of IL-35 in the serum and urine of recipients after renal transplantation are associated with the incidence of DGF to certain extent, prompting that excessively weak systemic and local anti-inflammatory responses early after renal transplantation and uncontrolled excessive inflammatory response are probably the pivotal causes of DGF.

Relationship between metabolic rate of tacrolimus and BK virus infection early after renal transplantation

Sun Zhongwei, Fan Yu, Bai Hongwei, Qian Yeyong

2018, 9(4): 278-282. doi: 10.3969/j.issn.1674-7445.2018.04.007

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Abstract:
Objective To investigate the relationship between the metabolic rate of tacrolimus (FK506) and BK virus infection early after renal transplantation. Methods Eighty recipients undergoing allogenic renal transplantation in Institute of Organ Transplantation of the 309^th Hospital of Chinese People' s Liberation Army were recruited in this study. The polymorphism of cytochrome P450 (CYP) 3A5 gene was detected in 80 recipients. All patients were divided into fast metabolism group (CYP3A5*1/*3 and CYP3A5*1/*1 genotypes, n=38) and slow metabolism group (CYP3A5*3/*3 genotype, n=42) based on the gene detection results. The distribution of CYP3A5 genotypes in 80 recipients was analyzed. The metabolic rate [concentration/dose ratio (C/D value)] of FK506 was statistically compared between two groups. The incidence of BK virus infection events [BK viruria, BK viremia and BK virus nephropathy(BKVN)] within postoperative 6 months were compared between two groups. Results Among 80 recipients, 5 cases (6%) were detected with CYP3A5*1/*1 genotype, 33 (41%) with CYP3A5*1/*3 genotype, and 42 (53%) with CYP3A5*3/*3 genotype. Among the 160 alleles in 80 recipients, 117 CYP3A5*3 allele were identified, suggesting that the mutation rate of CYP3A5*3 allele was 73.1%. In the fast metabolism group, the C/D values at postoperative 1, 3, and 6 months were significantly lower than those in the slow metabolism group (all P < 0.01). The incidence rates of BK viruria in the fast and slow metabolism groups were 37% and 29%, 18% and 2% for BK viremia, and 3% and 0 for BKVN, respectively. In the fast metabolism group, the incidence of BK virenia was significantly higher than that in the slow metabolism group (P=0.02). The incidence of BK viruria and BKVN did not significantly differ between two groups (both P > 0.05). Conclusions According to the CYP3A5 genotyping outcomes, the recipients with a high metabolic rate of FK506 have a high risk of BK viremia early after renal transplantation.

Experimental Researches

Preliminary study of the effect of EPO pretreatment of bone marrow mesenchymal stem cells on preventing acute rejection after renal transplantation in rats

Zhang Ya, Zhou Song, Liu Yongguang, Fan Lipei, Li Min, Guo Ying, Zhao Ming

2018, 9(4): 283-289. doi: 10.3969/j.issn.1674-7445.2018.04.008

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Abstract:
Objective To investigate the role of bone marrow mesenchymal stem cells (BMSCs) pretreated with erythropoietin (EPO) in the prevention of acute rejection after renal transplantation in rats. Methods BMSCs were divided into five groups: control group (without EPO), group A (pretreated with EPO at a final concentration of 10 IU/mL), group B (pretreated with EPO at a final concentration of 100 IU/mL), group C (pretreated with EPO at a final concentration of 500 IU/mL) and group D (pretreated with EPO at a final concentration of 1 000 IU/mL). In each group, the BMSCs were cultured for 24 h and 48 h. The proliferation rate of the BMSCs was determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The BMSCs were divided into two groups: BMSC group (without EPO) and EPO-BMSC group (pretreated with EPO at a final concentration of 500 IU/mL). After 48 h culture, Western blot was adopted to measure the expression level of CXC chemokine receptor (CXCR) 4 protein in BMSCs. Wistar rats were used as the donors, and SD rats were utilized as the recipients to establish the rat models with acute rejection after renal transplantation. The recipient rats were randomly divided into four groups (n=6 in each group) including the control group (without any intervention), EPO group (injection of 1 mL of solution containing 500 IU EPO via tail vein immediately after surgery), BMSC group (injection of 1 mL of solution containing 1×10⁶/mL BMSCs via tail vein immediately after surgery) and EPO-BMSC group (injection of 1 mL of solution containing 1×10⁶/mL BMSCs cultured in vitro with 500 IU/mL EPO via tail vein). The level of serum creatinine (Scr) level was determined by Scr detection kit. Western blot was used to detect the expression levels of interferon (IFN)-γ and interleukin (IL)-4 proteins. Results After 24 h culture, the proliferation rate of BMSCs did not significantly differ among all groups (all P > 0.05). After 48 h culture, the proliferation rate of BMSCs in group C (pretreated with EPO at a final concentration of 500 IU/mL) was significantly higher than that in the control group (P < 0.05). Compared with the BMSC group, the expression level of CXCR4 protein on the surface of BMSCs was higher in the EPO-BMSC group (P < 0.05). At 1 d after renal transplantation, the levels of Scr did not significantly differ among all groups (all P > 0.05). At 5 d after operation, the levels of Scr in the EPO, BMSC and EPO-BMSC groups were significantly lower than that in the control group (all P < 0.05). The level of Scr in the EPO-BMSC group was markedly lower than those in the EPO and BMSC groups (both P < 0.05). At postoperative 1 d and 5 d, the expression levels of IL-4 protein in the kidney tissues did not significantly differ among all groups (all P > 0.05). At 1 d after surgery, compared with control group, the expression levels of IFN-γ protein and IFN-γ/IL-4 ratio in the renal tissues in the EPO, BMSC and EPO-BMSC groups were significantly decreased to varying extents (all P < 0.05), and similar results were obtained at 5 d after surgery (all P < 0.05). The expression levels of IFN-γ protein and IFN-γ/IL-4 ratio in the EPO-BMSC group were significantly lower than those in the EPO group and BMSC group (both P < 0.05). Conclusions BMSCs pretreated with EPO can prevent the incidence of acute rejection after renal transplantation and protect the renal graft function.

Protective effect and mechanism of serum containing Euonymus fortunei on rat pancreatic islet cells

Jiang Peng, Gao Hongjun, You Jianpeng, Liang Taisheng, Gu Xinwei, Zhang Jianqiang, Liang Fangfang, Huang Fu, Wu Zhen

2018, 9(4): 290-296. doi: 10.3969/j.issn.1674-7445.2018.04.009

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Abstract:
Objective To investigate the protective effect and mechanism of serum containing Euonymus fortunei on the rat pancreatic islet cells. Methods Forty male SD rats were randomly divided into 5 groups (n=8 in each group), including the control group (normal rat islet cells were cultured with normal rat serum), ischemic preconditioning group (abdominal aorta was blocked first and then re-opened before the pancreas was obtained, and the pancreatic islet cells were cultured with normal rat serum), Euonymus fortunei treatment group (normal rat islet cells were cultured with rat serum containing Euonymus fortunei), Euonymus fortunei group and blank group (normal rats were administered orally with Euonymus fortunei extract or distilled water for the preparation of rat serum). Diphenylthiocarbazone (DTZ) staining was utilized to observe and calculate the quantity of islets. Acridine orange (AO)/propidium iodide (PI) staining was adopted to calculate the survival rate of islet cells. The insulin release experiment was performed to calculate the stimulation index (SI) and evaluate islet cell function. The concentration of glutathione (GSH) and nitric oxide (NO) in islet cells was detected using GSH and NO kits. The expression level of inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) was quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). Results Islet cells were observed in specifically scarlet color after DTZ staining. The quantity of islet cells did not significantly differ among different groups (all P > 0.05). Along with the prolongation of culture time, the activity of islet cells in each group was gradually decreased. At 72 h after isolation and culture, compared with the control group, the survival rate of the cells was significantly higher in the Euonymus fortunei treatment group (P < 0.05). The insulin release test results demonstrated that compared with the control group, the SI of the ischemic preconditioning and Euonymus fortunei treatment groups was significantly increased (both P < 0.05). Compared with the control group, the GSH contents of pancreatic islet cells in the ischemic preconditioning and Euonymus fortunei treatment groups were considerably enhanced, the NO content was significantly decreased, and the expression level of iNOS mRNA was significantly down-regulated (all P < 0.05). Conclusions Euonymus fortunei can increase the survival rate of islet cells and enhance the function of pancreatic islets by increasing the level of GSH, down-regulating the expression of iNOS and decreasing the NO production.

Effect and mechanism of mesenchymal stem cell derived from different sources on inhibiting follicular helper T cells

Kuang Guojie, Chen Wen, Shi Bingyi

2018, 9(4): 297-303. doi: 10.3969/j.issn.1674-7445.2018.04.010

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Abstract:
Objective To investigate the inhibitory effect and underlying mechanism of mesenchymal stem cell (MSC) derived from different sources on follicular helper T cell (Tfh cell). Methods Umbilical cord-derived MSC (UC MSC), bone marrow-derived MSC (BM MSC) and fat-derived MSC (Fat MSC) were co-cultured with peripheral blood mononuclear cell (PBMC) for 48 h. A control group was established. Flow cytometry was adopted to calculate the proportion of Tfh cells among the lymphocytes in four groups. The content of interleukin (IL)-21 in the supernatant was detected by enzyme-linked immune absorbent assay (ELISA) in four groups. BM MSC was co-cultured with PBMC, and supplemented with indoleamine 2, 3-dioxygenase (IDO) inhibitor 1-methyl tryptophan (1-MT), IL-10 antibody, human leukocyte antigen (HLA)-G antibody in the 1-MT group, IL-10 inhibition group, HLA-G inhibition group and BM MSC group without addition of other substances. After 48 h culture, flow cytometry was used to detect the percentage of Tfh cells among lymphocytes. Results Flow cytometry demonstrated that compared with the control group, the proportion of Tfh cells in the BM MSC group was significantly decreased (P < 0.05). Compared with the BM MSC group, the percentage of Tfh cells in the UC MSC and Fat MSC groups was significantly higher (both P < 0.05). ELISA revealed that compared with the control group, the IL-21 content in the BM MSC group was significantly decreased (P < 0.05). Compared with the BM MSC group, the IL-21 contents were considerably higher in the UC MSC and Fat MSC groups (both P < 0.05). The analysis of underlying mechanism revealed that the proportions of Tfh cells in the 1-MT, IL-10 inhibition and the HLA-G inhibition groups were (1.75±0.07)%, (1.31±0.09)% and (1.50±0.03)%, respectively, which were significantly higher than (1.03±0.43)% in the BM MSC group (all P < 0.05). Conclusions BM MSC exerts the highest inhibitory effect upon the differentiation of Tfh cell and IL-21. The mechanism underlying suppressing the differentiation of Tfh cells differentiation is probably correlated to promoting the secretion of IDO.

Summary of experience in the establishment of rat models with orthotopic liver transplantation from donation after cardiac death

Wu Ruichao, Huang Zhaoyu, Zhang Li, Liu Junhan, Zheng Kepu, Ran Jianghua

2018, 9(4): 304-310. doi: 10.3969/j.issn.1674-7445.2018.04.011

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Objective To explore the skills and summarize the experience in the establishment of orthotopic liver transplantation rat models from donation after cardiac death (DCD). Methods According to the time of warm ischemia, 120 rats were divided into 3 groups: group A (warm ischemia for 0 min, n=40 pairs), group B (warm ischemia for 10 min, n=40 pairs) and group C (warm ischemia for 20 min, n=40 pairs). Orthotopic liver transplantation was performed by the modified two-cuff technique in 3 groups. The time of each stage of surgery was recorded in 3 groups. The survival rate at the end of surgery, 24 h, 72 h and 7 d after surgery was recorded in 3 groups. The dead rats were immediately subject to anatomical examination to identify the cause of death. Results The cold ischemia time of donor liver, anhepatic phase and operation time of the recipients did not significantly differ among three groups (all P > 0.05). In groups A, B and C, the survival rate at the end of surgery was 97%, 97%, and 100% respectively. The survival rate at postoperative 24 h was 92%, 90% and 92% respectively. The survival rate at postoperative 72 h was 90%, 80% and 77% respectively. The survival rate at postoperative 7 d was 85%, 70% and 57% respectively. The survival rate at the end of surgery, postoperative 24 h and 72 h did not significantly differ among 3 groups (all P > 0.05). At postoperative 7 d, the survival rate in group C was significantly lower than that in group A (P < 0.05). Surgical operation was the major cause of intraoperative and postoperative 24 h death. Bile leakage and ischemic hepatic failure were the causes of death at postoperative 72 h. Biliary duct complications were the main causes of death at postoperative 7 d. The quantity of rats developing with biliary duct complications was increased along with the prolongation of warm ischemic time. Conclusions The success of stable establishment of rat models with orthotopic liver transplantation from DCD depends upon the protection of the liver and biliary function. The difficulty lies in the anastomosis of the suprahepatic inferior vena cava and the shortening of anhepatic phase.

Effect of tacrolimus on short chain fatty acids in rats

Huang Zhongli, Jiang Yamei, Song Turun, Wang Xianding, Fan Yu, Liu Jinpeng, Wang Zhiling, Wang Li, Lin Tao

2018, 9(4): 311-315. doi: 10.3969/j.issn.1674-7445.2018.04.012

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Objective To investigate the changes of short chain fatty acids (SCFA) induced by tacrolimus (FK506) in rats and evaluate its effect on blood glucose levels. Methods Ten SD rats were divided into the FK506 group and control group (n=5 in each group). In the FK506 group, the rats were received a subcutaneous injection of FK506 (3 mg/kg) +sunflower oil solution containing 10% ethanol daily for consecutive 4 weeks. In the control group, the rats were received a subcutaneous injection of an equivalent amount of sunflower oil solution containing 10% ethanol for consecutive 4 weeks. During the drug injection period, the body mass of rats was measured every week in two groups. After the drug injection period, blood glucose level, SCFA content in the blood and feces samples were measured in two groups. Results Compared with the control group, the relative body mass of rats in the FK506 group was significantly lower at the 2^nd, 3^rd and 4^th weeks (all P < 0.01). Compared with the control group, the blood glucose levels of rats in the FK506 group were significantly increased at 0, 30, and 60 min after giving glucose (P < 0.01-0.05). Compared with the control group, the contents of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid and valeric acid in the feces sample were significantly lower in the FK506 group (P < 0.01-0.05). Conclusions FK506 can upregulate the blood glucose level in rats, which is probably induced by the decrease of SCFA content in rat feces.