器官移植

Diagnosis and treatment of acute kidney injury after liver transplantation

Cai Jinzhen, Li Zhiqiang, Xu Chuanshen, Zhao Kai, Dai Deshu, Wang Xin

2023, 14(4): 473-478. doi: 10.3969/j.issn.1674-7445.2023.04.001

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Abstract:
Acute kidney injury is a common complication after liver transplantation, which severely affects clinical prognosis of liver transplant recipients. Multiple factors before, during and after liver transplantation may cause kidney injury. If not properly treated, it may progress into chronic kidney diseases, which significantly increases postoperative fatality and negatively affects clinical efficacy of liver transplantation. Therefore, prevention, diagnosis and treatment of acute kidney injury after liver transplantation is a hot topic for clinicians. In this article, the definition, diagnosis, risk factors, prevention and treatment of acute kidney injury after liver transplantation were reviewed, and potential risk factors and related therapeutic strategies during different stages of acute kidney injury after liver transplantation were analyzed, aiming to lower the risk of acute kidney injury after liver transplantation and further improve clinical prognosis of liver transplant recipients by optimizing treatment regimens.

Research status of machine perfusion of heart

Liu Jinping, Wang Wei

2023, 14(4): 479-484. doi: 10.3969/j.issn.1674-7445.2023.04.002

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High-quality donor heart is the prerequisite and fundamental guarantee for successful heart transplantation. Reasonable donor heart preservation technique plays a key role in improving the quality of donor heart and the prognosis of heart transplantation. Static cold storage (SCS) is currently the standard preservation technique for cardiac allograft. However, it is prone to cause severe cold ischemia injury to the donor heart, and it is impossible to evaluate heart function during SCS. As an important emerging technique of organ preservation, machine perfusion better matches with physiological conditions compared with SCS, which may remove metabolic wastes and provide basic substances for metabolic needs during organ preservation, prolong the preservation time and improve the preservation effect to a certain extent. Besides, it may also effectively evaluate organ function and improve clinical prognosis of heart transplantation. Meantime, it can also repair organ damage, significantly optimize organ quality and improve the utilization rate of donor organs. In this article, research status of machine perfusion of donor heart was reviewed.

Internal audit of Organ Procurement Organization under the requirements of high-quality development

Yang Shunliang, Lyu Lizhi, Jiang Zhelong, Li Yushu, Wang Dong, Wu Zaixin

2023, 14(4): 485-490. doi: 10.3969/j.issn.1674-7445.2023.04.003

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High-quality development is the primary task of building a socialist modern country in an all-round way. Organ donation and transplantation in China are evolving from high-speed growth to high-quality development, which put forward new requirements for the safe, stable and healthy operation of Organ Procurement Organization (OPO). Safety is the foundation and prerequisite for achieving the goal of high-quality development. As an independent and comprehensive department, internal audit should create new achievements in the new era. The department should include OPO and organ donation into the scope of internal audit, shift the emphasis upon the overall development of organ donation. Besides, it should fully consider the actual situation in different places, conduct all-round, objective and fair evaluation, provide evaluation and consulting services for OPO to properly implement organ donation, and give full play to the supervision and prevention role of internal audit.

Research progress on acute lung injury/acute respiratory distress syndrome after liver transplantation

Qiu Wei, Xia Xuxiang, Zhang Junpeng, Hu Xutao

2023, 14(4): 491-497. doi: 10.3969/j.issn.1674-7445.2023.04.004

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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common complication after liver transplantation, which could prolong the length of postoperative intensive care unit stay, affect clinical efficacy of liver transplantation and even lead to the death of recipients. ALI/ARDS has attracted extensive attention from liver transplant surgeons in clinical practice. ALI/ARDS after liver transplantation may be directly caused by pulmonary factors (such as mechanical ventilation-related lung injury, lung infection and aspiration, etc.) or indirectly induced by non-pulmonary factors (such as severe infection outside the lungs, blood transfusion and ischemia-reperfusion injury, etc.). In this article, the diagnostic criteria, incidence, mechanism, risk factors, laboratory and clinical diagnostic approaches and treatment of ALI/ARDS after liver transplantation were reviewed, aiming to deepen the understanding and cognition of ALI/ARDS during the perioperative period of liver transplantation and provide reference for the diagnosis and treatment of ALI/ARDS following liver transplantation.

Prevention and treatment of hepatic artery dissection in donors and recipients during liver transplantation

Liu Zhaobo, Wang Zhenshun, Liu Dongbin, Li Fei, Li Jia, Lin Dongdong

2023, 14(4): 498-504. doi: 10.3969/j.issn.1674-7445.2023.04.005

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Hepatic artery reconstruction is one of the key procedures in liver transplantation. Accidental dissection of the hepatic artery to be reconstructed caused by donor and recipient factors or surgical factors will disrupt the surgical plan, increase the difficulty of arterial reconstruction, significantly prolong the operation time, increase the risk of postoperative arterial stenosis and thrombosis and probably lead to acute allograft failure, which requires emergency surgical interventions or even secondary liver transplantation. Understanding of how to avoid dissection of the artery to be anastomosed during liver transplantation and corresponding treatment will contribute to preventing the incidence of artery-related complications during liver transplantation and improving clinical prognosis of liver transplant recipients. In this article, the causes, prevention and treatment of hepatic artery dissection and hepatic artery reconstruction in donors and recipients during liver transplantation were illustrated.

Research progress on application of artificial intelligence in the field of kidney transplantation

Ren Xiangge, Zhai Wensheng, Li Bing

2023, 14(4): 505-513. doi: 10.3969/j.issn.1674-7445.2023.04.006

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In recent years, artificial intelligence has been persistently developed and increasingly applied in the medical field, including risk prediction, diagnosis and treatment of various diseases, which enhances the diagnosis and management levels of diseases and shows a promising application prospect in the medical field. Artificial intelligence has been rapidly advanced in the field of kidney transplantation. Researchers have attempted to apply it in multiple scenarios, such as preoperative evaluation and prediction of postoperative complications of kidney transplantation, prompting that artificial intelligence has tremendous application prospect in the field of kidney transplantation. In this article, the application of artificial intelligence in donor-recipient matching, evaluation of renal allograft function, prediction of clinical outcomes, diagnosis of postoperative complications, monitoring and management of immunosuppressants were reviewed, research progress on the application of artificial intelligence in the field of kidney transplantation was summarized, and the limitations of artificial intelligence were discussed, aiming to provide reference for promoting the practical application and popularization of artificial intelligence in the field of kidney transplantation.

Application progress on contrast-enhanced ultrasound in acute rejection after kidney transplantation

Leng Qianghua, Han Fei, Huang Zhengyu

2023, 14(4): 514-520. doi: 10.3969/j.issn.1674-7445.2023.04.007

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Early diagnosis of acute rejection is of significance for the protection of renal allograft function. Pathological puncture biopsy is the gold standard for the diagnosis of acute rejection of renal allografts. Nevertheless, it may provoke multiple complications, such as bleeding, infection and renal parenchymal injury, which limit its widespread application. In recent years, the sensitivity of contrast-enhanced ultrasound in the diagnosis of acute rejection has been constantly improved. Ultrasound-targeted microbubble technique has further enhanced the diagnostic specificity of contrast-enhanced ultrasound, making it possible to replace pathological puncture biopsy. Besides, in the field of acute rejection treatment, microbubble ultrasonic cavitation may promote local delivery of immunosuppressants by inducing sonoporation and exhibit anti-rejection effect. In this article, the application of contrast-enhanced ultrasound in the diagnosis and treatment of acute rejection after kidney transplantation was reviewed, aiming to provide reference for widespread application of contrast-enhanced ultrasound in kidney transplantation.

Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation

Yang Shujun, Wei Hao, Xu Yong, Wang Heng'en, Song Xiangyu, Jia Zhibo, Peng Jiang, Cui Mengyi, Yang Boyao, Chen Leijia, Guo Aitao, Zhang Xiaoli, Pan Dengke, Du Jiaxiang, Shang Panfeng, Sun Shengkun

2023, 14(4): 521-528. doi: 10.3969/j.issn.1674-7445.2023.04.008

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Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K⁺ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β₂-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.

circSNRK alleviates ischemia-reperfusion injury in renal tubular epithelial cell by up-regulating Akt pathway

Meng Fanhang, Cui Ruiwen, Chen Qiuyuan, Gu Shijie, Cao Ronghua

2023, 14(4): 529-538. doi: 10.3969/j.issn.1674-7445.2023.04.009

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Objective To investigate the role and mechanism of circular RNA SNRK (circSNRK) in ischemia-reperfusion injury (IRI). Methods A hypoxia-reoxygenation (IRI) cell model was established. The expression level of circSNRK after IRI treatment and the effect of overexpression of circSNRK on cell proliferation and apoptosis were detected. The targets of circSNRK were identified. HK2 cells were divided into the blank group (Mock group), IRI group, control plasmid+IRI group (IRI+NC group), human circSNRK overexpression+IRI group (IRI+circSNRK group), human circSNRK overexpression+IRI+protein kinase B (Akt) inhibitor group (IRI+circSNRK+MK2206 group) and control plasmid group (NC group). Cell proliferation and apoptosis were detected in the Mock, IRI, IRI+NC and IRI+circSNRK groups. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the target of circSNRK were carried out. The expression levels of CDKN1A, Akt, B-cell lymphoma (Bcl)-2, cysteinyl aspartate specific proteinase (Caspase)-9 messenger RNA (mRNA), and those of p21, Bcl-2, Caspase-9, Akt and p-Akt proteins were detected in the Mock, IRI, IRI+NC and IRI+circSNRK groups, respectively. Cell proliferation and apoptosis were determined in the NC, IRI+NC, IRI+circSNRK and IRI+circSNRK+MK2206 groups. Results Compared with the Mock group, the expression level of circSNRK was lower, and cell proliferation capability of HK2 cells was decreased and cell apoptosis was increased in the IRI group. In the IRI+circSNRK group, cell proliferation capability was higher, whereas cell apoptosis was lower than those in the IRI+NC group. circSNRK could act on 648 targets through 51 microRNAs (miRNAs). GO enrichment analysis revealed that the targets of circSNRK were mainly enriched in biological processes (such as cell process and biological regulation), cell components (such as cell parts, cells and extracellular parts), and molecular functions (such as binding, binding proteins and enzymes). KEGG enrichment analysis showed that the targets of circSNRK were mainly enriched in cancer signaling pathway, phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, miRNA in cancer and other related signaling pathways. Compared with the Mock group, the relative expression levels of CDKN1A and Caspase-9 mRNA were higher, the expression level of miR-99a-5p RNA was higher and the relative expression levels of Akt and Bcl-2 mRNA were lower in the IRI group. Compared with the IRI+NC group, the relative expression levels of CDKN1A and Caspase-9 mRNA were lower, those of Akt and Bcl-2 mRNA were higher, and the expression level of miR-99a-5p RNA was lower in the IRI+circSNRK group, and the differences were statistically significant (all P < 0.05). Compared with the Mock group, the expression levels of p21 and Caspase-9 proteins were higher, while those of p-Akt, Akt and Bcl-2 proteins were lower in the IRI group. Compared with the IRI+NC group, the expression levels of p21 and Caspase-9 proteins were lower, whereas those of p-Akt, Akt and Bcl-2 proteins were higher in the IRI+circSNRK group. The miR-99a-5p binding sites were observed in circSNRK and Akt. Compared with the NC group, cell proliferation capability was declined in the IRI+NC group. Compared with the IRI+NC group, cell proliferation capability was elevated in the IRI+circSNRK group. Compared with the IRI+circSNRK group, cell proliferation capability was declined in the IRI+circSNRK+MK2206 group (all P < 0.05). The cell apoptosis level in the IRI+NC group was higher than that in the NC group. The cell apoptosis level in the IRI+circSNRK group was lower compared with that in the IRI+NC group. The cell apoptosis level in the IRI+circSNRK+MK2206 group was higher than that in the IRI+circSNRK group. Conclusions Under IRI conditions, circSNRK may affect the proliferation and apoptosis of HK2 cells probably via the Akt signaling pathway.

Dl-3-N-butylphthalide alleviates renal ischemia-reperfusion injury by down-regulating NF-κB signaling pathway and inhibiting cell pyroptosis in rat models

Zhang Ruibo, Shen Kaiwen, Wang Qiang, Yuan Qiang, Shen Jun

2023, 14(4): 539-546. doi: 10.3969/j.issn.1674-7445.2023.04.010

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Objective To elucidate the mechanism of dl-3-N-butylphthalide (NBP) on renal ischemia-reperfusion injury (IRI) in rat models. Methods Forty SD rats were randomly divided into the sham operation group (Sham group), model group (IRI group), NF-κB inhibitor pyrrolidine dithiocarbamate group (PDTC group), low-dose NBP group (NBP-L group) and high-dose NBP group (NBP-H group), with 8 rats in each group. Serum creatinine (Scr), serum cystatin C(Cys-C), blood urea nitrogen (BUN) and serum interleukin (IL)-1β and IL-18 levels were detected in all groups. Pathological injury of renal tissues in each group was observed by Hematoxylin-eosin (HE) staining. The expression levels of inflammatory factors and nuclear factor (NF)-κB signaling pathway and cell pyroptosis-related proteins in renal tissues were measured by Western blot and immunohistochemical staining. Results Compared with the Sham group, renal tissue injury was more severe, and the levels of Scr, Cys-C, BUN and serum IL-1β and IL-18 were all up-regulated in the IRI group. Western blot showed that the relative expression levels of NOD-like receptor protein (NLRP3), Gasdermin D(GSDMD), cysteinyl aspartate specific proteinase (Caspase)-1, IL-18, IL-1β, NF-κB p65 and p-NF-κB p65 proteins were all up-regulated, and immunohistochemical staining revealed that the expression levels of NF-κB p65 and p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were all up-regulated in the IRI group. Compared with the IRI group, renal tissue injury was alleviated, and the levels of Scr, Cys-C, BUN and serum IL-18 and IL-1β were down-regulated in the PDTC, NBP-L and NBP-H groups. Western blot showed that the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated, and immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the PDTC, NBP-L and NBP-H groups, respectively. Compared with the NBP-L group, renal tissue injury was mitigated, and the levels of Scr, Cys-C, BUN, serum IL-18 and IL-1β were all down-regulated in the NBP-H group. Western blot showed the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated in the NBP-H group. Immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the NBP-H group. Conclusions NBP may down-regulate the activity of NF-κB/NLRP3 signaling pathway and reduce the expression levels of cell pyroptosis-related proteins and inflammatory factors after renal IRI, thereby suppressing cell pyroptosis and alleviating renal IRI.

Intrapatient variability of tacrolimus trough concentrations and its effect on serum creatinine level in kidney transplant recipients treated with nematvir/ritonavir

Zhang Yan, Hu Linkun, Miao Liyan

2023, 14(4): 547-552. doi: 10.3969/j.issn.1674-7445.2023.04.011

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Objective To investigate the intra-patient variability (IPV) of tacrolimus trough concentrations and its effect on serum creatinine (Scr) level in kidney transplant recipients treated with nematvir/ritonavir. Methods Clinical data of 41 kidney transplant recipients infected by SARS-CoV-2 and treated with nematvir/ritonavir were collected. The usage of nematvir/ritonavir and tacrolimus was summarized. The distribution of tacrolimus trough concentrations and the attainment rate of target concentration were analyzed. The correlation between the IPV distribution of tacrolimus trough concentrations and the changes of Scr level was determined. Results Among 41 kidney transplant recipients, 46%(19/41) were given with full- and low-dose nematvir/ritonavir, and 7%(3/41) were given with high-dose nematvir/ritonavir. Use of tacrolimus was discontinued at 24 h before nematvir/ritonavir treatment in 95%(39/41) patients, and at 24 h after use of nematvir/ritonavir in 5%(2/41) patients. Tacrolimus was given at least 3 d after the 5-d course of nematvir/ritonavir in all patients. The attainment rate of tacrolimus trough concentration was 73%(30/41), 30%(3/10), 48%(15/31), 35%(11/31) and 53%(16/30) before, during, 1 week, 2 weeks and 1 month after use of nematvir/ritonavir, respectively. The median IPV was 35%(23%, 51%). Spearman correlation analysis showed that the increase of Scr level was positively correlated with IPV (r_s=0.400 7, P=0.028 2). Conclusions The attainment rate of tacrolimus trough concentration is declined in kidney transplant recipients treated with nematvir/ritonavir. The IPV of tacrolimus trough concentrations is elevated. The recipients with higher IPV are prone to an elevation in Scr level.

Analysis of effect of preoperative renal insufficiency on clinical prognosis of heart transplant recipients

Zheng Shanshan, Huang Jie, Zheng Zhe, Liao Zhongkai, Song Yunhu, Liu Sheng

2023, 14(4): 553-561. doi: 10.3969/j.issn.1674-7445.2023.04.012

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Objective To evaluate the effect of renal insufficiency before heart transplantation on perioperative death, complications and long-term survival, and to compare the differences between preoperative serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) in preoperative risk assessment. Methods Clinical data of 1 095 heart transplant recipients were retrospectively analyzed. According to preoperative Scr level, all recipients were divided into the Scr < 133 μmol/L(n=980), Scr 133-176 μmol/L (n=83) and Scr≥177 μmol/L groups (n=32). According to preoperative eGFR, all recipients were divided into eGFR≥90 mL/(min·1.73m²) (n=436), eGFR 60-89 mL/(min·1.73m²) (n=418) and eGFR < 60 mL/(min·1.73m²) groups (n=241). Clinical prognosis of postoperative renal function, perioperative and long-term outcomes of recipients were compared among different groups. The effect of eGFR and Scr level on renal function injury and long-term survival after heart transplantation was assessed. Results With the increase of preoperative Scr level, the proportion of recipients undergoing postoperative continuous renal replacement therapy (CRRT) was increased, the proportion of recipients receiving postoperative mechanical circulatory support was elevated, the incidence of postoperative complications was increased, the duration of mechanical ventilation and intensive care unit(ICU) stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). With the decrease of preoperative eGFR, the proportion of recipients receiving postoperative CRRT was increased, the proportion of recipients using postoperative intra-aortic balloon pump (IABP) was elevated, the duration of mechanical ventilation and ICU stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). Scr≥177 μmol/L was an independent risk factor for postoperative death [adjusted hazard ratio (HR) 3.64, 95% confidence interval (CI) 1.89-6.99, P < 0.01]. Among different groups classified by Scr and eGFR, the cumulative incidence rate of postoperative renal function injury and long-term survival rate were statistically significant among three groups (all P < 0.05). In patients with preoperative Scr < 133 μmol/L, the cumulative incidence rate of postoperative long-term renal function injury was significantly increased with the decrease of preoperative eGFR (P < 0.01). There was no significant difference in postoperative long-term survival rate among patients stratified by different eGFR (P > 0.05). Conclusions Renal insufficiency before heart transplantation is associated with poor perioperative and long-term prognosis. Preoperative Scr and eGFR are the independent risk factors for postoperative renal function injury. Scr yields low sensitivity in the assessment of preoperative renal function, whereas it has high accuracy in predicting perioperative death risk. And eGFR is a more sensitive parameter to evaluate preoperative renal function, which may identify early-stage renal functional abnormality and take effective measures during early stage to reduce adverse effect on prognosis.

In vitro research of mesenchymal stem cell-coated human islets to alleviate instant blood-mediated inflammatory reaction

Yang Yuwei, Li Wanli, Chen Jibing, Feng Bingzheng, Xu Zhiran, Wu Lingling, Wu Zhen, Gu Xinwei, Gao Hongjun

2023, 14(4): 562-569. doi: 10.3969/j.issn.1674-7445.2023.04.013

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Objective To evaluate the effect of mesenchymal stem cell (MSC) coated-islets on instant blood-mediated inflammatory reaction (IBMIR) after islet transplantation. Methods MSC labeled with tracer and human islets were placed into an ultra-low adsorption cell culture dish, shaken and mixed twice at an interval of 0.5 h, and then incubated at 37 ℃ and 5% CO₂ for 24 h to obtain MSC-coated islets. The coating effect of MSC and in vitro function of the islets were assessed. A blood circulation tube-shaped model was established in vitro. In the blank control group, 0.2 mL of islet culture solution was added. In the islet group, 800 islet equivalent quantity (IEQ) of uncoated islets were supplemented. In the MSC-coated islets group, 800 IEQ of MSC-coated islets were added, and circulated for 60 min at 37 ℃. A portion of 0.5 mL blood sample was taken for routine blood test at 0, 30 and 60 min, respectively. After 60 min circulation, the blood sample was filtered with a 70 μm filter to collect plasma, blood clots and islets. Blood clots and islets were subject to hematoxylin-eosin (HE) staining and immunohistochemical staining. Morphological changes and the aggregation of CD11b-positive cells surrounding the islets were observed. The contents of plasma thrombin-antithrombin complex (TAT), tissue factor (TF), C3a, C5b-9, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1 and IL-8 were determined by enzyme-linked immune absorbent assay. Results After 24 h co-incubation, the islets were coated by MSC, with a coating degree of approximately 80%. In the islet and MSC-coated islet group, a large quantity of neutrophils and monocytes were observed surrounding the blood clots and islets, and the quantity of CD11b-positive cells in the MSC-coated islet group was less compared with that in the islet group. After co-incubation with the whole blood for 0, 30 and 60 min, the quantity of platelets, neutrophils and monocytes was declined in the MSC-coated and islet groups, and gradually decreased over time. Compared with the blank control group, the quantity of platelets, monocytes and neutrophils was lower, whereas the TF content was higher in the MSC-coated islet group. Compared with the islet group, the quantity of platelets, monocytes and neutrophils was higher, whereas the TAT and TF contents were less in the MSC-coated islet group, the differences were statistically significant (all P < 0.05). Compared with the blank control group, the expression levels of C3a, C5b-9, IL-6, TNF-α and IL-8 were up-regulated in the MSC-coated islet group. Compared with the islet group, the expression levels of C3a, C5b-9, IL-1β, IL-6, TNF-α, IL-8 and MCP-1 were down-regulated in the MSC-coated islet group, and the differences were statistically significant (all P < 0.05). Conclusions MSC-coated islets may reduce the exposure of islet TF in the blood and prevent the incidence of IBMIR during the coagulation response stage, thereby mitigating the injury and loss of islet allograft in the early stage of islet transplantation.

Clinical and epidemiological features analysis of pneumocystis jirovecii pneumonia in kidney transplant recipients

Shen Ze, Tian Yangyang, Zhou Zheng, Hui Yu, Wang Liangliang, Pan Hao, Huang Yuhua, Hu Linkun

2023, 14(4): 570-577. doi: 10.3969/j.issn.1674-7445.2023.04.014

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Objective To investigate clinical and epidemiological features of pneumocystis jirovecii pneumonia (PJP) in kidney transplant recipients. Methods Clinical data of 68 kidney transplant recipients admitted from July, 2021 to December, 2021 were collected. All patients were divided into the PJP group (n=11), common pulmonary infection group (n=24) and non-pneumonia group (n=33) according to the status of pulmonary infection. The incidence and treatment of PJP after kidney transplantation were analyzed. Basic characteristics and laboratory parameters of the recipients were compared among all groups. The genotyping and transmission map of PJP patients were evaluated. Results Among 64 kidney transplant recipients, 11 cases were definitely diagnosed with PJP. The most common clinical manifestations included elevated body temperature, and dry cough complicated with progressive dyspnea. Chest CT scan showed diffuse interstitial inflammation and ground glass-like lesions of bilateral lungs in all patients. After diagnosis, all patients were orally given with compound sulfamethoxazole for 3-4 weeks. Two patients received non-invasive ventilator-assisted ventilation due to severe lung infection and dyspnea, and the remaining patients were given with nasal cannula oxygenation. One patient experienced elevated serum creatinine level upon discharge, and developed renal allograft failure. The remaining 10 recipients with PJP obtained normal renal allograft function, and no recipient died. Compared with the non-pneumonia group, the rejection rate was higher, the length of hospital stay was longer, the lymphocyte count was less, the lymphocyte proportion was lower, the levels of C-reactive protein, serum creatinine and lactate dehydrogenase were higher, and the levels of serum albumin was lower and CD4⁺T cell count was less in the PJP group (all P < 0.05). Compared with common pulmonary infection group, the lymphocyte count was less, the lymphocyte proportion was lower, the CD4⁺T cell count was less and 1, 3-β-D- glucan (BDG) level was higher in the PJP group (all P < 0.05). No new genotype was detected in 10 of the 12 testing samples. It was considered that PJP mainly depended on two transmission chains and two independent transmission individuals. Conclusions Kidney transplant recipients are prone to pneumocystis jirovecii (PJ) infection due to impaired cellular immune function. The most common clinical manifestations consist of elevated body temperature and dry cough complicated with progressive dyspnea, accompanied by headache and fatigue in partial patients. Chest CT scan shows diffuse interstitial inflammation and ground glass-like lesion of bilateral lungs. PJ may be transmitted through respiratory tract. Small-scale PJP might occur in the follow-up outpatient of kidney transplant recipients. Preventive measures should be delivered in a timely manner.

Analysis of risk factors of multidrug-resistant organism infection in lung transplant recipients based on restricted cubic spline model

Qiu Sangsang, Xu Qinfen, Chen Jingyu, Liu Feng, Huang Qinhong, Li Xiaoshan, Wu Bo

2023, 14(4): 578-584. doi: 10.3969/j.issn.1674-7445.2023.04.015

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Objective To summarize current status of multidrug-resistant organism (MDRO) infection in lung transplant recipients and analyze the risk factors of MDRO infection. Methods Clinical data of 321 lung transplant recipients were retrospectively analyzed. According to the incidence of postoperative MDRO infection, they were divided into the MDRO group (n=122) and non-MDRO infection group (n=199). The incidence of MDRO infection in lung transplant recipients was summarized. The risk factors of MDRO infection in lung transplant recipients were analyzed by logistic regression model. The dose-response relationship between MDRO infection and time of ventilator use was determined by restricted cubic spline model. Results Among 321 lung transplant recipients, 122 cases developed MDRO infection, with an infection rate of 38.0%. Two hundred and twenty-nine strains of pathogenic bacteria were detected in the MDRO infection group, mainly Gram-negative bacteria (92.6%), and the top three strains were carbapenem-resistant acinetobacter baumannii (46.3%), carbapenem-resistant pseudomonas aeruginosa (22.3%) and carbapenem-resistant klebsiella pneumoniae (14.8%), respectively. MDRO infection mainly consisted of lower respiratory tract infection (61.5%), followed by ventilator-associated pneumonia (26.2%). Univariate analysis showed that the risk factors of MDRO infection in lung transplant recipients were single-lung transplantation, long-time postoperative use of extracorporeal membrane oxygenation (ECMO), long operation time, long-time urinary catheterization, long-time central venous catheterization and long-time ventilator use (all P < 0.05). Multivariate logistic regression analysis indicated that single-lung transplantation and long-time ventilator use were the independent risk factors for MDRO infection in lung transplant recipients (both P < 0.05). Results of restricted cubic spline model analysis showed that the risk of infection continued to increase with the prolongation of ventilator use time within 20 d. After 20 d, prolonging the time of ventilator use failed to increase the risk of infection, showing a plateau effect. Conclusions The MDRO infection rate tends to decline in lung transplant recipients year by year. Single-lung transplantation and long-time ventilator use are the independent risk factors for MDRO infection in lung transplant recipients.

Latest research progress on expansion of the donor pool for heart transplantation

Yuan Shun, Wang Zhiwei

2023, 14(4): 585-591. doi: 10.3969/j.issn.1674-7445.2023.04.016

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Abstract:
With gradual maturity of surgical technique of heart transplantation, extensive use of immunosuppressants and the improvement of organ distribution system, the shortage of donor heart has become a bottleneck issue restricting the development of heart transplantation in clinical practice. How to expand the donor pool for heart transplantation remains to be urgently solved. In recent years, with the development of science and technology and the application of new technology, groundbreaking progresses have been made on how to expand the donor pool for heart transplantation within the transplantation community. Multiple research results have been gradually translated into clinical practice, driving the development of heart transplantation in clinical settings. In this article, the latest technologies and strategies to expand the donor pool for heart transplantation were reviewed, the roles of organ preservation technology, use of marginal donor heart, xenotransplantation, artificial heart and bioartificial heart in alleviating the shortage of donor heart were investigated, and existing challenges and future directions to expand the donor pool for heart transplantation were summarized, aiming to provide reference for subsequent development of heart transplantation in clinical practice.

Potential value of mesenchymal stem cells and their derivatives in repairing donor liver

Wang Yiting, Jiang Jie, Ma Li, Hu Zongqiang, Li Li

2023, 14(4): 592-597. doi: 10.3969/j.issn.1674-7445.2023.04.017

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Abstract:
In recent years, organ transplantation has developed rapidly in China, whereas the proportion of supply and demand of organs for donation is severely unbalanced. To resolve the shortage of donor livers, repairing extended criteria donor liver and improving the quality of donor liver are critical research directions. Mesenchymal stem cell (MSC) is a category of stem cells with self-renewal and differentiation potential, which possess the functions of immunomodulation and tissue repair. The derivatives of MSC have the advantages of low immunogenicity and high biocompatibility, which have been widely applied in the treatment of multiple diseases. In this article, research progress on the role of MSC, exosomes and extracellular vesicles in alleviating liver steatosis, repairing ischemia-reperfusion injury and promoting the regeneration of small-for-size liver allograft was reviewed, and the feasibility and safety of MSC and the derivatives in repairing donor liver were summarized, aiming provide novel ideas for repairing marginal donor liver and enhancing the quality of liver allograft.

The role of mammalian target of rapamycin inhibitor in virus infection of organ transplant recipients

Du Chunkai, Zhu Yichen, Lin Jun

2023, 14(4): 598-604. doi: 10.3969/j.issn.1674-7445.2023.04.018

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Abstract:
At present, mammalian target of rapamycin (mTOR) inhibitors are commonly-used immunosuppressive drugs after organ transplantation, including sirolimus (rapamycin) and everolimus. mTOR inhibitors not only exert an immunosuppressive effect by inhibiting T cell proliferation, but also possess multiple potential functions, such as antiaging, anti-tumor and anti-virus infection, etc. Virus infection is one of the most common complications after organ transplantation. Current anti-viral treatments are limited and yield poor efficacy. In this article, the role of mTOR pathway in virus infection, the mechanism of common mTOR inhibitors and the role of mTOR inhibitors in different types of virus infections were reviewed, aiming to provide reference for clinical application and subsequent research of mTOR inhibitors in organ transplant recipients.

Current status and prospect of preoperative assessment of heart disease risk in liver transplant recipients

Li Wenlei, Li Guangming

2023, 14(4): 605-611. doi: 10.3969/j.issn.1674-7445.2023.04.019

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Abstract:
With the changes of the disease spectrum of liver transplantation and organ allocation system, more and more patients complicated with cardiovascular complications have entered the waiting list for liver transplantation. However, surgical stress, severe infection and adverse reactions of immunosuppressive drugs will significantly increase the risk of postoperative cardiac complications and affect the short-and long-term survival of the recipients. Therefore, comprehensive evaluation of cardiac structure and function of the recipients before liver transplantation is of significance for improving clinical prognosis of the recipients. In this article, the main causes for the increased risk of heart disease during the perioperative period of liver transplantation, the time and methods of heart disease risk assessment for liver transplant recipients were reviewed, and existing assessment approaches for common heart diseases before liver transplantation were illustrated, aiming to provide reference for further reducing the incidence of heart complications after liver transplantation, improving the survival rates of grafts and recipients and enhancing clinical prognosis.

Application progress in classification of puncture biopsy after kidney transplantation

Halinuer Shadekejiang, Dong Jin, Wu Xiongfei, Zhu Jiefu

2023, 14(4): 612-618. doi: 10.3969/j.issn.1674-7445.2023.04.020

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Abstract:
Renal allograft biopsy (biopsy) remains the "gold standard" for the diagnosis of renal dysfunction after kidney transplantation. Puncture biopsy after kidney transplantation could be divided into indicative biopsy and protocol biopsy according to renal function of the patients. Indicative biopsy is mainly applied to diagnose postoperative complications of kidney transplantation, evaluate the severity of disease and guide subsequent treatment. Protocol biopsy is primarily employed to regular monitor renal allograft function of kidney transplant recipients and exclude subclinical rejection and other complications. Due to the willingness of patients and other reasons, protocol biopsy has not been widely applied in China. Currently, indicative biopsy is the main biopsy pattern. At present, the indications of puncture of indicative biopsy, the timing and necessity of puncture of protocol biopsy remain controversial. In this article, the classification of puncture biopsy after kidney transplantation and research progress on tissue biomarkers based on biopsy were reviewed, aiming to assist clinical diagnosis and targeted treatment of complications after kidney transplantation and provide reference for further improving the survival of renal allografts and recipients.

Minutes of seminar on 2023 multi-center cooperation project of liver transplantation for metastatic liver cancer in China

Teng Fei, Song Shaohua, Fu Zhiren

2023, 14(4): 619-622. doi: 10.3969/j.issn.1674-7445.2023.04.021

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Abstract:
Led by Zheng Shusen, Academician of Chinese Academy of Engineering (CAE) from Zhejiang University, the first multi-center cooperation project of liver transplantation for metastatic liver cancer in China, gathering 28 liver transplantation centers nationwide, was launched in Shanghai. All participating experts conducted in-depth exchanges and discussions regarding four topics including inclusion criteria of liver transplantation for metastatic liver cancer, the risk assessment and prognostic evaluation of liver transplantation for metastatic liver cancer, perioperative medication of liver transplantation for metastatic liver cancer, and the implementation details of multi-center cooperation project. Questionnaires were distributed to reach consensus and pinpoint the directions, aiming to carry out high-quality and standardized clinical researches on liver transplantation for metastatic liver cancer in China.

2023 Vol. 14, No. 4