器官移植

Establishment of quality management system of Organ Procurement Organization with Chinese characteristics

Li Yushu, Yang Shunliang

2021, 12(4): 369-375. doi: 10.3969/j.issn.1674-7445.2021.04.001

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Abstract:
Quality assurance is the responsibility of Organ Procurement Organization (OPO). The establishment of OPO quality management system is a novel task for implementing high-quality human organ donation. At present, the quality management of OPO still has certain problems, such as lack of comprehensive management organization, standardized management process, scientific evaluation index, qualified professionals and strong safety culture atmosphere, etc. It is necessary to deliver top-level design from three perspectives of ideological concept change, quality management system construction and process implementation management in combination with the actual situation of OPO and reference to the criteria of international general quality management system. More importantly, the managers of OPO should play a leading role in ensuring the efficient operation of OPO in the persistent improvement of quality management system.

Overview of global organ donation and transplantation in 2020

Jiang Wenshi, Sun Yongkang, Yan Juan, Jiang Feng, Wang Huiying, Ma Qiruo, Xie Ying, He Xiangxiang, Wu Xiaotong

2021, 12(4): 376-383. doi: 10.3969/j.issn.1674-7445.2021.04.002

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Objective At present, the novel coronavirus pneumonia (COVID-19) pandemic is still raging in certain regions around the globe, and the prevention and control of the pandemic should be strengthened. Under the challenges of respective social environment and allocation of medical resources, and support from the inertia and inherent productivity of the system on which the industry depends, extensive attempts are being delivered to push forward the work of organ donation and transplantation in each country. Under the guidance of national experts and committee members, Shanxi Provincial Human Organ Procurement and Allocation Service Center was established on August 28, 2018 approved by the former Shanxi Provincial Health and Family Planning Commission. It is the only independent non-profit medical institution in Shanxi Province. In this article, the system construction of citizen's organ donation and transplantation fitting national and provincial conditions was further explored according to the data analysis of organ donation and transplantation in the United States and Spain during the COVID-19 pandemic combined with the implementation of organ donation work in Shanxi Provincial Human Organ Procurement and Allocation Service Center.

The latest progress on donation after the circulatory determination of death at home and abroad

Chen Gang, Han Ming, He Xiangxiang, Jiang Wenshi

2021, 12(4): 384-390. doi: 10.3969/j.issn.1674-7445.2021.04.003

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Organ shortage is a common problem in the field of transplantation worldwide. It is urgent to expand the donor pool via different effective and safe approaches. Recently, "the statement from international collaborative on expanding controlled donation after the circulatory determination of death (cDCDD)" has attracted widespread attention from scholars. The statement aims to promote cDCDD in order to increase organ donation rates, with the ultimate goal of achieving self-sufficiency in transplantation. In this article, the key contents mentioned in the statement were summarized, the terminology update and relevant discussion of donation after the circulatory determination of death (DCDD), the development trend of DCDD, the basic part of the clinical pathway of cDCDD and the key factors affecting the implementation of cDCDD were illustrated, and the inspiration drew from this statement to the sustainable development of organ donation program in China was reflected.

Progress on electron microscopy diagnosis on Banff classification for renal allograft pathology

Huang Yabing, Guo Hui, Guan Yang, Zhong Weixiong

2021, 12(4): 391-396. doi: 10.3969/j.issn.1674-7445.2021.04.004

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With the development of organ transplantation in clinical practice, allograft pathology has been constantly developing and advancing. The convening of Banff conference on allograft pathology and the establishment of Banff classification on allograft pathology (Banff classification) are pivotal milestones in the development of international allograft pathology. Since then, Banff classification on pathological diagnosis of various transplant organs have been continually updated and improved. Ultrastructural pathological observation by electron microscope plays an irreplaceable role in the early diagnosis of antibody-mediated rejection, recurrent disease and de novo disease of renal allograft. Early detection and rational treatment help to maintain the long-term survival of renal allograft and reduce the failure of renal allograft. In this article, the basic definition of electron microscope and the ultrastructural pathological diagnosis, the research history and main progress on electron microscope diagnosis on Banff classification for renal allograft pathology were introduced, and typical pathological changes, specific terminology and diagnostic criteria of electron microscope diagnosis on renal allograft biopsy were summarized, aiming to provide reference for clinical and basic research of organ transplantation.

Research status and prospect of basic application of islet organoid

Wu Lingling, Jiang Peng, Wu Zhen, Li Wanli, Yang Yuwei, Gao Hongjun

2021, 12(4): 397-402. doi: 10.3969/j.issn.1674-7445.2021.04.005

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Organoids are tissue structures, generated from pluripotent stem cells and cultured in vitro, which form self-organize and recapitulate tissues with similar structure and function to the original organs. Organoids have similar appearance and function to the original tissues, and have been widely applied in basic research and clinical trial. At present, the organoids of liver, kidney, islet, brain, intestine and other organs have been successfully cultivated. The use of islet organoid is a hotspot in the field of organoid research. However, islet organoid is currently applied in basic research because rejection after organ transplantation and other issues remain unresolved. In this article, the origin, development and basic application of islet organoid were reviewed, aiming to provide reference for the transformation from basic research of islet organoid into clinical application as well as the treatment of diabetes mellitus.

Experimental study of effect and mechanism of cysteine rich protein 61 on survival of adipose tissues in rats after autologous fat grafting

Chen Zhaohuan, Duan Ran, Huang Xiaolu, Li Qingfeng

2021, 12(4): 403-411. doi: 10.3969/j.issn.1674-7445.2021.04.006

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Objective To evaluate the effect and mechanism of cysteine rich protein 61, namely CCN family member 1(CCN1) on the survival of adipose tissues in rats after autologous fat grafting. Methods At 1 week after the establishment of autologous fat grafting rat models, all animals were randomly divided into the CCN1 group (n=20) and control group (n=20). The survival of fat grafts, the morphology of fat graft tissues, the proportion of active adipocytes and the number of new blood vessels of rats were statistically compared between two groups. The levels of differential expressed messenger ribonucleic acid (mRNA) in the fat graft tissues of rats were compared between two groups by high-throughput sequencing and subsequently subject to cluster analysis. The expression levels of related proinflammatory cytokines of fat graft tissues of rats were statistically compared between two groups. Results The weight retention rate of adipose tissues in the CCN1 group was significantly higher than that in the control group (P < 0.05). In the CCN1 group, the integrity of adipocytes was considerably higher, the degree of vesiculation and vacuolation, the degree of inflammatory cell aggregation and the degree of fibrosis were significantly lower than those in the control group (all P < 0.000 1). Immunofluorescence staining demonstrated that the proportion of active adipocytes with uniform morphology was higher in the CCN1 group, whereas the proportion of active adipocytes was lower and the cells were observed in different sizes accompanied by vesiculation in the control group. Compared with the control group, the quantity of new blood vessels was significantly higher, and the expression levels of platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) mRNA were remarkably higher in the CCN1 group (all P < 0.05). High-throughput sequencing analysis showed that the data at the transcriptome levels significantly differed between two groups. In the CCN1 group, the gene expression levels of cell surface markers, inflammatory cytokines and chemokines related to M1 macrophages tended to decline. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) revealed that the mRNA expression levels of interleukin (IL)-8, IL-1 and Toll-like receptor (TLR) 2 in the CCN1 group were significantly lower than those in the control group (P < 0.01-0.05). Conclusions During autologous fat grafting, supplement of exogenous CCN1 may effectively promote the neovascularization of adipose tissues and improve the survival rate of fat graft probably by mediating the transformation of macrophages into M2 phenotype via down-regulating the TLR2 expression level.

Effect of phosphoglycerate mutase 5 mediated pyroptosis on liver ischemia-reperfusion injury

Qiao Bingbing, Li Shipeng, Song Haosen, Ji Min, Zhao Longshuan

2021, 12(4): 412-420. doi: 10.3969/j.issn.1674-7445.2021.04.007

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Objective To investigate the effect and its molecular mechanism of phosphoglycerate mutase 5 (PGAM5) mediated pyroptosis on liver ischemia-reperfusion injury (IRI). Methods C57 mouse models of liver IRI were established and randomly divided into the 6 h reperfusion (6 h group) and 12 h reperfusion (12 h group), and sham operation group (sham group) was established too, 10 rats in each group. The effect of IRI on the parameters in the liver tissues and serum samples was evaluated. The expression levels of PGAM5 and cysteinyl aspartate specific proteinase (Caspase)-1 in the liver tissues during IRI were quantitatively detected. The IRI models of liver cells were established (IRI group). The IRI models of liver cells were established after pretreatment with Caspase-1 inhibitor Z-YVAD-FMK (inhibitor group). The untreated AML12 cells were allocated into the control group. The effect of inhibiting Caspase-1 activity on pyroptosis was analyzed. AML12 cells were transfected with PGAM5 small interfering ribonucleic acid (siRNA) (siRNA group) and siRNA-negative control (siRNA-NC) (siRNA-NC group) by liposome 3000, and then IRI models of liver cells were established. The untreated AML12 cells were assigned into the control group. The effect of PGAM5 mediated pyroptosis on IRI of liver cells was assessed. Results In the 6 h and 12 h groups, partial liver cell edema, hepatic sinusoid narrowing, central vein congestion and occasional spot necrosis were observed in the mouse liver tissues, and these changes in the 12 h group were more aggravated than those in the 6 h group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 h and 12 h groups were higher than those in the sham group, and the values in the 12 h group were higher than those in the 6 h group. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were increased in the 6 h and 12 h groups, and the values in the 12 h group were lower than those in the 6 h group. The relative expression levels of IL-1β messenger ribonucleic acid (mRNA) in the mouse liver tissues in the 6 h and 12 h groups were up-regulated, and the value in the 12 h group was lower than that in the 6 h group. The cell apoptosis rates in the liver tissues were significantly increased in the 6 h and 12 h groups, and the value in the 12 h group was remarkably lower than that in the 6 h group (P < 0.01-0.05). Compared with the sham group, the relative expression levels of PGAM5 mRNA and protein in the mouse liver tissues in the 6 h and 12 h groups were significantly up-regulated, and the values in the 12 h group were significantly higher than those in the 6 h group (P < 0.01-0.05). The protein expression levels of PGAM5 and Caspase-1 in the liver tissues were up-regulated in the 6 h and 12 h groups. Compared with the control group, the relative expression levels of NOD-like receptor protein 3 (NLRP3), cleaved Caspase-1 and Gasdermin D (GSDMD) proteins were up-regulated and the fluorescence intensity of GSDMD was increased in the IRI group. Compared with the IRI group, the relative expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated and the fluorescence intensity of GSDMD was considerably decreased in the inhibitor group (P < 0.01-0.05). Compared with the control group, the cell survival rate was significantly decreased, and the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly up-regulated in the siRNA-NC group (P < 0.01-0.05). Compared with the siRNA-NC group, the cell survival rate was remarkably increased, whereas the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated in the siRNA group (P < 0.01-0.05). Conclusions PGAM5 may aggravate the liver IRI in mouse models probably by mediating pyroptosis via PGAM5/Caspase-1/GSDMD signaling pathway and aggravating liver cell injury.

Experimental study on the role of IL-10 in improving donor lung function after ex vivo lung perfusion in rats of cardiac death

Chen Yinglun, Wei Dong, Wang Zitao, Yang Xiucheng, Liu Mingzhao, Dai Zhenhang, Chen Jingyu

2021, 12(4): 421-427. doi: 10.3969/j.issn.1674-7445.2021.04.008

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Objective To evaluate the effect of interleukin (IL)-10 on donor lung function after ex vivo lung perfusion (EVLP) in rats of cardiac death. Methods Twenty adult male SD rats were randomly divided into the simple perfusion group (group A, n=10) and modified perfusion group (group B, n=10). Perfusate A (without IL-10) and perfusate B (supplemented with IL-10) was administered in group A and B, respectively. The EVLP rat models of cardiac death were established. The appearance of donor lung, dry-to-wet (D/W) ratio of donor lung tissues, the function and metabolism of donor lung, the morphology of donor lung and the levels of inflammatory markers of donor lung were statistically compared between two groups. Results After perfusion, evident edema of the whole donor lung, poor compliance and a large amount of edema fluid discharged from the airway were observed in group A, whereas no obvious edema and good compliance were found in group B. Compared with group A, the D/W ratio of lung tissues in group B was higher (P < 0.05). In both groups, the pulmonary vein partial pressure of oxygen reached the peak at 2 h after perfusion, which did not significantly differ between two groups (P > 0.05). In group B, the pulmonary artery pressure was increased at a lower speed and significantly lower after perfusion, and the lactic acid level in the perfusate was significantly lower than those in group A (all P < 0.05). In group A, the alveolar structure was largely destroyed and the cells was rare. In group B, the alveolar structure was relatively normal without evident cell edema. The incidence of cell apoptosis of donor lung was high in group A, whereas no obvious cell apoptosis of donor lung was noted in group B. After perfusion for 4 h, the levels of monocyte chemoattractant protein (MCP)-1 and IL-6 were significantly increased, the IL-4 levels were remarkably decreased (all P < 0.05), but the levels of tumor necrosis factor (TNF)-α, IL-1α and inducible nitric oxide synthase (iNOS) did not significantly change in both groups (all P > 0.05). Conclusions IL-10 may improve the function of donor lung after EVLP in rat of cardiac death by reducing cell apoptosis.

Mechanism of Danhong injection in improving therapeutic effect of neural stem cell transplantation for cerebral ischemia injury

Wang Jiachuan, Yu Xuewen, Xu Hua, Li Zhenguo, Xu Zhouwen, Shao Mumin

2021, 12(4): 428-435. doi: 10.3969/j.issn.1674-7445.2021.04.009

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Objective To investigate whether Danhong injection can enhance the therapeutic effect of neural stem cell (NSC) transplantation in repairing cerebral ischemia injury by regulating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Methods Forty male SD rats were randomly divided into the NSC transplantation group (NSC group), Danhong injection group (DH group), NSC+ Danhong injection group (N+D group), NSC+ Danhong injection group +ML385 group(N+D+M group) and PBS control group (PBS group), 8 rats in each group. All rat models of cerebral ischemia were established by embolization of the middle cerebral artery. Reperfusion was performed at 1.5 h after embolization. All rats in each group received corresponding interventions at 3 d after reperfusion. The neurological function score was evaluated before and 1, 2, 4 weeks after NSC transplantation. All rats were sacrificed at 4 weeks after NSC transplantation. The parameters related to oxidative stress were detected. The expression levels of neuron-specific nuclear protein (NeuN) and von Willebrand factor (vWF) were determined by immunofluorescence staining. Results Before NSC transplantation, the neurological function scores did not significantly differ among different groups (all P > 0.05). At postoperative 1, 2 and 4 weeks, the neurological function scores in the NSC, DH and N+D groups were significantly lower than those in the PBS and N+D+M groups (all P < 0.05). Compared with the PBS and N+D+M groups, the malondialdehyde (MDA) levels were significantly decreased, whereas the superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels were considerably increased in the NSC, DH and N+D groups (all P < 0.05). The GPX level in the N+D+M group was significantly lower than that in the PBS group (P < 0.05). Immunofluorescence staining showed that the transplant NSC in the rat brain migrated to the surrounding area of cerebral infarction and survived, and expressed neuronal marker NeuN and neovascularization marker vWF. However, the number of living NSC in the N+D+M group was significantly lower compared with those in the remaining groups. Conclusions Danhong injection may improve the microenvironment of stem cell transplantation, enhance the survival rate of transplant NSC and improve the therapeutic effect of NSC transplantation for cerebral ischemia injury probably by regulating the Nrf2 signaling pathway.

Protective effect of sevoflurane preconditioning on lung ischemia-reperfusion injury in rats and its influence on TLR4/MyD88/NF-κB signaling pathway

Fan Junchao, Song Junjie, Chen Yong

2021, 12(4): 436-444. doi: 10.3969/j.issn.1674-7445.2021.04.010

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Objective To evaluate the protective effect of sevoflurane preconditioning on lung ischemia-reperfusion injury (IRI) and its influence on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor (NF)-κB signaling pathway. Methods Forty healthy adult SD rats were randomly divided into the control group (Sham group), lung IRI model group (LIRI group), sevoflurane group (Sev group) and TLR4 inhibitor TAK-242 combined with sevoflurane group (TAK+Sev group), 10 rats in each group. The pathological changes of lung tissues were observed by hematoxylin-eosin (HE) staining and the pathological injury score was graded. The cell apoptosis of lung tissues was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick- end labeling (TUNEL) and the apoptosis rate was calculated. The wet-to-dry (W/D) ratio of lung tissues was measured to determine the water content of lung tissues. The levels of oxidative stress-related parameters in the lung tissues and inflammatory factors in both the lung tissues and serum were detected. The expression levels of TLR4/MyD88/NF-κB signaling pathway-associated proteins in the lung tissues were determined by Western blot. Results Compared with the Sham group, the pathological injury score, W/D ratio, cell apoptosis rate, malondialdehyde (MDA) level, inflammatory factor level and the relative expression levels of TLR4, MyD88 and NF-κB p65 proteins in the lung tissues were significantly increased, whereas the superoxide dismutase (SOD) level and the relative expression level of NF-κB inhibitory protein α(IκBα) were significantly decreased in the LIRI and Sev groups (all P < 0.05). Compared with the LIRI group, the pathological injury score, W/D ratio, cell apoptosis rate, MDA level, inflammatory factor level and the relative expression levels of TLR4, MyD88 and NF-κB p65 proteins were significantly decreased, whereas the SOD level and the relative expression level of IκBα were significantly increased in the Sev and TAK+Sev groups (all P < 0.05). Compared with the Sev group, the pathological injury score, W/D ratio, cell apoptosis rate, MDA level, inflammatory factor level and the relative expression levels of TLR4, MyD88, NF-κB p65 proteins were significantly decreased, while the relative expression level of IκBα was significantly increased in the TAK+Sev group (all P < 0.05). Conclusions Sevoflurane preconditioning may inhibit the activation of TLR4/MyD88/NF-κB signaling pathway and suppress inflammatory reaction and oxidative stress, thereby effectively mitigating the lung IRI.

Safety of PD-1 inhibitor in preoperative treatment of liver transplantation for liver cancer

Liu Zhaobo, Wu Jushan, Lin Dongdong, Li Guangming

2021, 12(4): 445-449. doi: 10.3969/j.issn.1674-7445.2021.04.011

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Objective To evaluate the safety of programmed cell death protein 1 (PD-1) inhibitor in the treatment of primary liver cancer (liver cancer) before liver transplantation. Methods Clinical data of 7 recipients given with PD-1 inhibitor before liver transplantation for liver cancer were retrospectively analyzed. The incidence of immune-related adverse event (irAE) and clinical prognosis of the recipients were summarized. The safety of PD-1 inhibitor in recipients prior to liver transplantation for liver cancer was evaluated. Results Seven recipients were treated with PD-1 inhibitor with 1-20 courses before liver transplantation for liver cancer. The time interval from drug withdrawal to liver transplantation was 6-120 d. Five recipients suffered from irAE of different degrees, including fatigue in 3 cases, fever in 2 cases, alopecia in 2 cases, rash in 1 case, nausea in 1 case and myocarditis in 1 case, respectively. A majority of these irAE were classified as grade Ⅰ-Ⅱ. One recipient died from grade Ⅴ irAE (fatal myocarditis). One recipient developed rejection at postoperative 7 d, which were mitigated after glucocorticoid pulse therapy combined with increased dosage of tacrolimus. Conclusions PD-1 inhibitor can be applied in preoperative treatment before liver transplantation for liver cancer. Nevertheless, the incidence of irAE and postoperative rejection should be intimately monitored.

Early outcomes of heart transplantation in critical patients: single center experience of Fuwai Hospital

Zheng Shanshan, Liu Sheng, Tang Hanwei, Song Yunhu, Wang wei, Huang Jie, Liao Zhongkai, Zheng Zhe

2021, 12(4): 450-457. doi: 10.3969/j.issn.1674-7445.2021.04.012

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Objective To analyze the early outcomes of heart transplantation in critical patients and its significance in donor allocation decision. Methods Clinical data of 449 recipients undergoing heart transplantation were retrospectively analyzed. According to preoperative status, all patients were divided into the critical status group (n=64) and general status group (n=385). The incidence of critical status was summarized. Clinical data of recipients were statistically compared between two groups. Postoperative survival and causes of death in recipients between two groups were analyzed. Perioperative results of critical recipients undergoing different mechanical circulation support as a bridge to heart transplantation were compared. Results Critical patients accounted for 14.3% of the total number of transplant recipients. The proportion of critical patients gradually increased in recent 5 years. Compared with the general status group, the recipients in critical status group had a lower proportion of smoking history, a higher proportion of cardiac surgery history, a higher serum level of creatinine, and a higher proportion of primary diseases of heart failure before heart transplantation(all P≤0.01). The proportion of undergoing mechanical circulation support was higher, the incidence of complications was higher, the stay time in intensive care unit (ICU) was longer and the in-hospital fatality was higher after heart transplantation in the critical status group (all P≤0.01). The 1-year survival rate of recipients in critical status group was significantly lower than that in general status group (83% vs. 95%, P < 0.01). The fatality of recipients due to infection and multiple organ failure in critical status group was higher than that in general status group. Among 64 critical recipients, 1 recipient received ventilator alone, and 63 recipients underwent mechanical circulation support devices as a bridge to heart transplantation. Among them, intra-aortic balloon pump (IABP) alone was applied in 49 cases (77%), 8 cases (13%) of extracorporeal membrane oxygenation (ECMO) combined with IABP, 4 cases (6%) of ECMO alone, and 2 cases (3%) of left ventricular assist device (LVAD) alone. Critical patients who received preoperative ECMO and ECMO combined with IABP bridging to heart transplantation have a higher proportion of postoperative complications, a longer ICU stay time, a longer mechanical ventilation time, and a higher proportion of hospital deaths. Conclusions The overall prognosis of critical patients undergoing heart transplantation is relatively poor. Effective preoperative management may reverse the high-risk status of critical patients in a certain extent. The limited quantity of donor heart should be allocated to the most urgent patients who can obtain the greatest benefit from heart transplantation.

Three-dimensional speckle tracking imaging for quantitative evaluation of left ventricular global strain in renal transplant recipients

Tang Junyi, Sui Mingxing, Xi Jiaying, Zhu Xialing, Cai Zhuhong, Jin Xiucai

2021, 12(4): 458-464. doi: 10.3969/j.issn.1674-7445.2021.04.013

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Objective To evaluate the application value of three-dimensional speckle tracking imaging (3D-STI) in quantitatively evaluating the left ventricular global strain in recipients within 3 months after renal transplantation. Methods Clinical data including blood pressure, serum creatinine and tacrolimus blood concentration of 34 renal transplant recipients were collected before operation, 7 d, 1 month and 3 months after operation, respectively. Meanwhile, conventional echocardiography and 3D-STI examination were performed. Echocardiographic parameters [left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF)] and 3D-STI parameters [left ventricular global peak longitudinal strain (GPLS), global peak circumferential strain (GPCS), global peak radial strain (GPRS) and global peak area strain (GPAS)] of recipients were collected. The changes of these parameters before operation, 7 d, 1 month and 3 months after operation were statistically compared. The changing characteristic and application value of 3D-STI in quantitatively evaluating the left ventricular global strain in recipients within 3 months after renal transplantation were evaluated. Results LVEF and GPCS did not significantly differ at different time points (all P > 0.05), whereas LVEDV, LVESV, GPLS, GPAS and GPRS significantly differed at different time points from preoperative to within postoperative 3 months (all P < 0.001). GPLS, GPAS and GPRS trended to decline within postoperative 1 month, and slightly increased at 3 months after operation, which was still lower than the preoperative levels. Conclusions Application of 3D-STI may sensitively detect the changes of left ventricular global strain in recipients after renal transplantation when no significant variations are observed in postoperative LVEF. Compared with conventional echocardiography, 3D-STI may more accurately evaluate the changes of left ventricular global strain in recipients after renal transplantation.

Multi-disciplinary team of human herpes virus-6B encephalitis after liver transplantation

Guo Yafei, Wang Jizhou, Zhu Zebin, Chen Cui, Liu Guoyan, Qun Sen, Deng Kexue, Huang Dehao, Liu Lianxin

2021, 12(4): 465-471. doi: 10.3969/j.issn.1674-7445.2021.04.014

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Objective To evaluate the role of multi-disciplinary team (MDT) in improving the diagnosis and treatment of human herpes virus-6B (HHV-6B) encephalitis after liver transplantation. Methods MDT consultation was delivered for one rare case of HHV-6B encephalitis after liver transplantation to establish an effective individualized treatment regime. Results On the 16 d after liver transplantation, the patient developed headache, and suddenly presented with unresponsiveness, unconsciousness, coma complicated with involuntary limb twitching on the 18 d. Blood ammonia level was increased. Brain CT scan showed cerebral ischemic changes. Electroencephalography prompted the epileptic seizure. After MDT consultation, the possibility of nervous system infection after liver transplantation was considered, and medication therapy was given to control the epileptic seizure. Cerebrospinal fluid examination via lumbar puncture hinted increased intracranial pressure. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) of the cerebrospinal fluid demonstrated that the patient was tested positive for HHV-6B nucleic acid, which confirmed the diagnosis of HHV-6B encephalitis. The immunosuppressant regime was adjusted, intravenous ganciclovir was given for antiviral treatment, and active interventions were delivered to prevent and treat relevant complications. Epileptic seizure disappeared after 4 d, and neurological symptoms were significantly alleviated after 2 weeks. After 4-week antiviral treatment, the patient was tested negative for virology testing, and the neurological function was restored to normal. Conclusions HHV-6B encephalitis rarely occurs after adult liver transplantation, which is primarily associated with the virus reactivation after use of immunosuppressant. MDT pattern may be employed to deepen the understanding of the patient's condition, formulate more effective individualized treatment regime, and enhance the clinical efficacy and safety.

Role of PD-1/PD-L1 signaling pathway in immune response of liver transplantation

Lu Jing, Xu Junming

2021, 12(4): 472-476. doi: 10.3969/j.issn.1674-7445.2021.04.015

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Primary liver cancer (liver cancer) is one of the main indications of liver transplantation. However, postoperative recurrence of liver cancer severely affects the long-term clinical efficacy of liver transplantation. Programmed cell death protein 1 (PD-1) is an immunosuppressive molecule. Activation of PD-1/programmed cell death protein-ligand 1 (PD-L1) signaling pathway plays a pivotal role in the immune tolerance of grafts. In recent years, immune checkpoint inhibitor(ICI), such as PD-1/PD-L1 inhibitor, has become one of the effective approaches to treat advanced liver cancer, whereas ICI can be applied in liver transplant recipients is highly controversial, and the efficacy and safety remain to be studied. In this article, the expression of PD-1/PD-L1 in liver allograft tissues, the mechanism of PD-1/PD-L1 inducing transplantation immune tolerance and clinical application of PD-1/PD-L1 inhibitor in liver transplantation for liver cancer were reviewed.

Application progress of extracellular vesicle in liver transplantation

Jia Degong, Jia Zhixing, Guo Shanshan, Cheng Ying

2021, 12(4): 477-483. doi: 10.3969/j.issn.1674-7445.2021.04.016

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Liver transplantation is an effective treatment of end-stage liver diseases. However, liver ischemia-reperfusion injury (IRI) and rejection significantly cause the decrease of survival rate of liver graft. Therefore, it is urgent to explore a novel method, which can not only alleviate liver IRI, but also promote immune tolerance of allograft, thereby improving the survival rate of liver graft. Extracellular vesicle (EV) is nanoparticle released from cells into the extracellular microenvironment, which may alleviate graft injury by repairing autophagy, immunosuppression and accelerating tissue regeneration. Hence, EV becomes a research hot spot in the field of liver transplantation. Nevertheless, the clinical application of EV encounters multiple challenges, such as separation, purification, identification, storage of EV and how to deliver EV to the target cells. In this article, the mechanism of EV in liver IRI, the challenges in clinical application of EV and the potential application of EV were reviewed, aiming to provide reference for the clinical application of EV in liver transplantation.

The latest progress on JC virus infection after renal transplantation

He Yu, Ou Zhiyu, Miao Yun

2021, 12(4): 484-488. doi: 10.3969/j.issn.1674-7445.2021.04.017

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JC virus (JCV) is a member of polyomaviridae family that infects approximately 70% of the population worldwide. JCV constantly stays in a latent state after the primary infection. In immunosuppressed individuals, especially under the circumstances of low cellular immune function, JCV may be reactivated and lead to severe clinical manifestations. In recent years, the correlation between JCV and complications after renal transplantation has captivated widespread attention. JCV-associated nephropathy (JCVAN) has been reported. Here, latest research progresses on the epidemiology, molecular biology, in vivo infection process, JCV and complications after renal transplantation, and the relationship between JCV and BKV were reviewed, aiming to provide reference for the adjustment of immunosuppressive regimen following renal transplantation.

Research progress on determination of intracellular concentration of immunosuppressant

Shao Kun, Chen Bing, Zhou Peijun

2021, 12(4): 489-495. doi: 10.3969/j.issn.1674-7445.2021.04.018

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Abstract:
Currently, extracellular concentration measurement is the major approach of therapeutic drug monitoring (TDM) of clinical immunosuppressant in organ transplantation. Its correlation with the efficacy of immunosuppressant remains elusive. With widespread application of liquid chromatography, the detection technology of intracellular concentration of immunosuppressant is gradually mature. Theoretically, it may more accurately reflect the efficacy of immunosuppressant due to that the level of drug exposure in target cells can be directly measured. In this article, the history and present situation of the determination of intracellular concentration of immunosuppressant were summarized, and the association between the determination methods of intracellular concentration of immunosuppressant and drug efficacy was emphatically analyzed. Detection of intracellular concentration of immunosuppressant possesses better application value in clinical practice, which is worthy of promotion in clinical settings.

Research progress on the gene polymorphism of tacrolimus transporter in organ transplantation

Zhang Hanshu, Song Cangsang, Zhang Yang, Li Xingde

2021, 12(4): 496-502. doi: 10.3969/j.issn.1674-7445.2021.04.019

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Abstract:
Tacrolimus (Tac) is a commonly used immunosuppressant after organ transplantation, which has high immunosuppressive efficacy. However, the pharmacokinetics of Tac significantly differ among individuals, and gene polymorphism is the main influencing factor. In recent years, the gene polymorphism of drug transporter has become a novel research hotspot. Nevertheless, the effect of the gene polymorphism of transporter on Tac pharmacokinetics remains controversial. Consequently, the correlation between the gene polymorphism of transporter and Tac blood concentration plays a significant role in guiding Tac-based individualized immunosuppressive therapy. In this article, the research progresses on the gene polymorphism of adenosine triphosphate-binding cassette (ABC) transporter and solute carrier (SLC) transporter in organ transplantation was reviewed. The correlation between the gene polymorphism of transporter and Tac blood concentration was summarized, aiming to provide reference for Tac-based individualized therapy.

2021 Vol. 12, No. 4