器官移植

Abstract:
Objective To investigate the effect of induced pluripotent stem cells (iPSCs) transplantation after the down-regulation of hypoxia-inducible factor (HIF)-2α gene on the treatment of cerebral ischemia injury in rats. Methods Twenty-four male Sprague-Dawley (SD) rats were randomly and evenly divided into the iPSCs treatment, iPSCs+siHIF-2α and phosphate buffer saline (PBS) control groups. The rat models with cerebral ischemia were established by the middle cerebral artery embolization, and reperfusion was carried out 90 min after embolization. At 3 d after reperfusion, iPSCs transplantation, iPSCs+siHIF-2α transplantation or PBS injection were performed. Before and at 2 and 4 weeks after transplantation, neurobehavioral evaluation was performed and the uptake of ¹⁸F-fluoro-deoxyglucose (¹⁸F-FDG) was measured by micro-positron emission tomography (micro-PET). At 4 weeks after transplantation, the rats were sacrificed and nerve cell markers were detected by immunofluorescence. Results At 2 and 4 weeks after stem cell transplantation, the neurological function scores of the iPSCs treatment group were significantly lower than those in the PBS control group (both P < 0.05), whereas the neurological function scores in the iPSCs+siHIF-2α group were considerably higher than those in the iPSCs treatment group (both P < 0.05). At 2 and 4 weeks after stem cell transplantation, the glucose metabolism levels (injured side/normal side) in the brain of cerebral ischemia rats in the iPSCs treatment and iPSCs+siHIF-2αgroups were significantly increased compared with those in the PBS control group (both P < 0.001). At the 2^nd week after stem cell transplantation, the glucose metabolism level in the iPSCs treatment group was significantly higher than that in the iPSCs+siHIF-2α group (P < 0.001). Subsequently, the glucose metabolism level in the iPSCs+siHIF-2α group continued to rise until the 4^th week after stem cell transplantation, which was almost identical to but still lower than that in the iPSCs treatment group (P=0.025). Immunofluorescent staining prompted that the transplanted stem cells survived and migrated to the periphery of the infarction area, and a majority of the transplanted stem cells expressed nerve cell markers. Conclusions iPSCs transplantation can be employed to effectively treat cerebral ischemia injury in rats. Down-regulation of HIF-2α gene exerts certain effect upon the therapeutic effect of iPSCs transplantation.

Effect and mechanism research of selective deletion of Ndst1 in donor kidney on acute rejection after renal transplantation in mouse models

Li Xuemei, Gu Baohong, Hu Jike, Ma Yanling, Wang Bofang, Feng Zedong, Zhang Fan, Chen Hao

2018, 9(6): 424-429. doi: 10.3969/j.issn.1674-7445.2018.06.005

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Abstract:
Objective To investigate the effect and mechanism of selective deletion of N-deacetylase-N-sulfotransferase (Ndst) 1 in donor kidney on the acute rejection after renal transplantation in the recipient mice. Methods A mouse model undergoing renal transplantation was established. The mice were divided into 3 groups according to the strains of mice and treatment: wild type (WT) group (n=10), Ndst1^-/- group (n=9) and myxoma virus T7 protein(M-T 7)treatment group (n=7). The mice were euthanized at postoperative 10 d. Pathological examination and the content of disaccharide [heparan sulfate (HS) and chondroitin sulfate (CS)] in glycosaminoglycans (GAGs) were analyzed. The correlation between pathological score and changes of disaccharide content was analyzed. Results Compared with the WT group, the overall pathological scores of early rejection of the transplanted kidney tissues were significantly lower in the Ndst1^-/- and M-T7 treatment groups (both P < 0.05). Compared with the WT group, the percentage of 6-O sulfation and the content of D0S6 in HS were significantly increased, whereas the contents of D0A4 and D2A4 in CS were significantly decreased in the transplanted kidney tissues in the Ndst1^-/- group (all P < 0.05). Compared with the WT group, the percentage of 6-O sulfation in HS, the percentages of 6-O sulfation and 2-O sulfation in CS and the contents of D0S6 and D2S6 in HS were significantly increased, whereas the content of D2A0 in HS, the contents of D0A4 and D2A4 in CS were significantly decreased in the transplanted kidney tissues in the M-T7 treatment group (all P < 0.05). The changes of disaccharide content in the transplanted kidney tissues of mice were significantly correlated with pathological scores related to acute rejection (all P < 0.05). Conclusions Selective deletion of Ndst1 of the donor kidney can alleviate acute rejection after renal transplantation, and the mechanism may be related to the increased 6-O sulfation ratio of disaccharide HS in the transplanted kidney tissues.

Clinical Researches

Application of LifePort organ transporter to improve clinical efficacy of renal transplantation: a report of 573 cases

Pan Xiaoming, Xue Wujun, Tian Puxun, Ding Xiaoming, Xiang Heli, Feng Xinshun, Yan Hang, Hou Jun, Tian Xiaohui, Li Yang, Ding Chenguang

2018, 9(6): 430-435, 477. doi: 10.3969/j.issn.1674-7445.2018.06.006

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Abstract:
Objective To evaluate the effect of the preservation of the donor kidneys from donation after cardiac death (DCD) and expanded criteria donor (ECD) by donor kidney pulse perfusion storage transporter (LifePort) on the postoperative recovery of renal function in recipients undergoing renal transplantation. Methods Perioperative clinical data of 466 donors (DCD+ECD) and 882 recipients undergoing renal transplantation were retrospectively analyzed. According to different approaches of kidney preservation, bilateral kidneys of 309 DCD donors were randomly divided into the LifePort group(DCD-LP, n=309) and DCD cold storage group (n=309). All the bilateral kidneys of 132 ECD donors were stored and transported by LifePort and assigned into the ECD-LP group (n=264). The postoperative overall condition, early postoperative renal function indexes and postoperative complications of the recipients were observed among three groups. The pathological findings of renal puncture before renal transplantation were observed in donor kidneys. The LifePort perfusion parameters of the donor kidney were compared between the recipients with and without delayed graft function (DGF) after renal transplantation. Results Compared with the DCD cold storage group, the length of hospital stay was significantly shorter in the DCD-LP and ECD-LP groups (both P < 0.05). The survival rate of the recipients was 100% in three groups. The survival rate of the donor kidney was 99.7%, 100% and 99.2% in the DCD cold storage, DCD-LP and ECD-LP groups, respectively. No statistical difference was observed among three groups (all P > 0.05). Compared with the DCD cold storage group, the incidence of DGF was significantly lower in the DCD-LP and ECD-LP groups (both P < 0.05). Early postoperative renal function, the incidence of acute rejection, infection and surgical complications did not significantly differ among three groups (all P > 0.05). Pathological examination demonstrated that usage of LifePort perfusion could significantly mitigate the edema, degeneration and necrosis of renal tubules. In the recipients with DGF, the LifePort perfusion resistance index of donor kidney was significantly higher, whereas the LifePort perfusion volume of donor kidney was considerably lower than those without DGF (both P < 0.05). Conclusions LifePort can effectively improve the quality of the donor kidney from DCD and ECD in vitro, reduce the incidence of postoperative DGF, promote the recovery of transplanted kidney function and predict the postoperative recovery during the maintenance and evaluation of the isolated kidney.

Effect of mycophenolate mofetil and enteric-coated mycophenolate sodium on blood concentration in renal transplant recipients

Zeng Weisheng, Zhang Changsheng, Song Mi, Zhu Min, Li Tonghai, Li Zhen

2018, 9(6): 436-440. doi: 10.3969/j.issn.1674-7445.2018.06.007

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Abstract:
Objective To evaluate the effect of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) on the blood concentration of mycophenolic acid (MPA) and adverse events in renal transplant recipients at the equivalent biologically effective dose. Methods Clinical data of 106 recipients undergoing living-donor kidney transplantation were retrospectively analyzed. According to the drugs taken after renal transplantation, all recipients were divided into the MMF (M1 group, n=62) and EC-MPS groups (M2 group, n=44). In the M1 group, tacrolimus (FK506) + MMF + prednisone was delivered and FK506 + EC-MPS + prednisone was given in the M2 group. The changes of blood concentration of MPA were analyzed at 1-, 2-, 3-week, 1-, 2- and 3-month after drug administration. The incidence of adverse events and the drug cost were also analyzed. Results The drugs were administered at the same biologically effective dose. At each time point after drug administration, the trough blood concentration of MPA in the M1 group was significantly lower than that in the M2 group (all P < 0.05). Compared with the M1 group, the incidence and severity of adverse events were significantly less in the M2 group. The cost of taking MMF in the M1 group was 1 710 Yuan/month, whereas 2 736 Yuan/month for taking EC-MPS in the M2 group. However, the cost of treating drug-induced adverse events in the M1 group was significantly higher than that in the M2 group. Conclusions Patients taking EC-MPS at the same biologically effective dose can maintain higher blood concentration of MPA and suffer from fewer adverse events than their counterparts receiving MMF.

Secondary transplantation strategy for graft failure of haploidentical hematopoietic stem cell transplantation for acute lymphocytic leukemia

Zhang Jingwen, Sun Yanling, Li Xudong

2018, 9(6): 441-444. doi: 10.3969/j.issn.1674-7445.2018.06.008

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Abstract:
Objective To explore the secondary transplantation strategy for graft failure of the primary haploidentical hematopoietic stem cell transplantation (haplo-SCT) associated with fatal complications in a patient with acute T-cell lymphocytic leukemia. Methods One male patient was diagnosed with acute T-cell lymphocytic leukemia. In November 2015, he received haplo-SCT from his sister as the donor. But graft failure was developed and complicated by Escherichia coli sepsis, serum disease, hepatic venous occlusion and multiple organ failure. At 32^nd d after the first transplantation, secondary haplo-SCT from his father as the donor was performed. Prior to secondary transplantation, chemotherapy pretreatment was not conducted. Post-transplantation cyclophosphamide (PTCy)-based prevention measure against the graft-versus-host disease (GVHD) was adopted after transplantation. Results White blood cells were implanted on the 12nd d and platelet implantation was performed on the 67th d after haplo-SCT. Serum disease, septicemia and hepatic venous occlusion were cured and organ function was improved. However, the patient died from the recurrence of leukemia at 18^th months after transplantation (June 2017). Conclusions Prior to secondary haplo-SCT, PTCy prevention measures against the GVHD rather than pretreated chemotherapy probably contributes to the success of transplantation.

Investigation of influencing factors of residents' willingness to donate organs in Yantai City and conception of novel propaganda mode

Geng Zixiang, Niu Tianfu, Gao Shuchang, Zheng Yu, Han Chunlei

2018, 9(6): 445-450. doi: 10.3969/j.issn.1674-7445.2018.06.009

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Abstract:
Objective To explore the influencing factors of the willingness of residents to donate organs in Yantai City and to devise an effective propaganda mode for organ donation. Methods The residents of 10 districts and counties in Yantai City were chosen for survey investigation by convenient sampling method. The survey items included socio-demographic characteristics, ways to obtain organ transplantation and organ donation related knowledge, relevant factors affecting the willingness to donate organs, and relevant issues of potential apprehension, etc. During the survey, a novel propaganda mode of organ donation called Chengguang mode was established. Results The awareness of organ donation of Yantai residents was relatively low and 44.6% of residents were willing to donate organs. Age and educational level affected the residents' willingness to donate organs (both P < 0.05). Most residents learned the knowledge about organ donation through TV, radio and internet. The correct rate of residents to answer the questions related to organ donation was relatively low. Traditional ideas (38.1%) and public opinions (25.9%) were the main factors affecting the residents' willingness to donate organs. The opposition of family members significantly reduced the organ donation rate of residents, whereas financial compensation and social assistance greatly increased their willingness to donate organs. Only 16.3% of the residents knew the way for organ donation through Alipay, suggesting the propaganda was insufficient. In the process of survey investigation, a novel propaganda mode, Chengguang mode, initiated by local medical college and university and then gradually promoted nationwide, was established. Conclusions The willingness to donate organs of residents in Yantai City is mainly influenced by the cognition level of organ donation. It is necessary to strengthen the propaganda of organ donation. A new propaganda mode started by local medical college and promoted throughout the nation is established to enhance the understanding and participation in organ donation, thereby probably improving the organ donation rate across China.

Total pancreatectomy-islet autotransplantation in treatment of chronic pancreatitis: report of one case and literature review

Chen Huanwei, Luan Xiaojun, Liu Chengyang, Xiao Ping, Zhen Zuojun, Deng Feiwen, Wang Fengjie, Liu Ying, Xu Xuejuan, Chen Guoqiang

2018, 9(6): 451-455. doi: 10.3969/j.issn.1674-7445.2018.06.010

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Abstract:
Objective To evaluate the clinical efficacy of total pancreatectomy-islet autotransplantation (TP-IAT) in the treatment of chronic pancreatitis. Methods One patient diagnosed with refractory chronic pancreatitis complicated with multiple pseudocysts and pancreatic stones underwent TP-IAT in the First People's Hospital of Foshan. Clinical data were collected and analyzed during postoperative 3 months follow-up. Results The patient was well recovered after TP-IAT without complications, such as bleeding and severe hypoglycemia. Abdominal pain was completely relieved without taking analgesic drugs. During postoperative follow-up, the patient was treated with exogenous insulin, the fasting blood glucose was properly controlled and the function of islet cells was partially restored. Conclusions TP-IAT can not only relieve the clinical symptoms of chronic pancreatitis, but also prevent postoperative diabetes mellitus, which is an efficacious treatment of refractory chronic pancreatitis.