2022 Vol. 13, No. 5

Guideline and Consensus
Expert consensus on liver transplantation perioperative evaluation and rehabilitation for acute-on-chronic liver failure
Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association, Organ Transplant Rehabilitation Committee of China Association Rehabilitation Medicine, Branch of Organ Transplantation Physician of Guangdong Medical Doctor Association
2022, 13(5): 543-554. doi: 10.3969/j.issn.1674-7445.2022.05.001
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Acute-on-chronic liver failure (ACLF) can be cured by liver transplantation; however, perioperative complications still affect posttransplant outcomes. In recent years, early rehabilitation for critical illness, liver disease, and surgery have significantly improved organ reserve function, surgery tolerance, and postoperative quality of life. They could also be applied in the perioperative period of liver transplantation in patients with ACLF. Therefore, the Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association, the Organ Transplant Rehabilitation Committee of China Association Rehabilitation Medicine, and the Branch of Organ Transplantation Physician of Guangdong Medical Doctor Association conducted a comprehensive review of rehabilitation in end-stage liver disease, critical illness and surgical patients by summarizing current evidence and best clinical practices and proposed a practice consensus on evaluation of cardiopulmonary and physical function, rehabilitation or physiotherapies, as well as the safety concerns in perioperative liver transplant recipients. It will be a valuable resource for hepatologists, transplant surgeons, and intensivists as they care for ACLF patients during transplantation.
Editorial
Diagnosis and treatment of vascular complications after liver transplantation in adults
Zhang Jiabin, Li Guangming
2022, 13(5): 555-560. doi: 10.3969/j.issn.1674-7445.2022.05.002
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As an efficacious treatment for end-stage liver diseases and primary malignant liver tumors, liver transplantation has been widely applied worldwide, and gradually receives widespread recognition from patients. With the development of organ transplant technique, vascular complications have rarely occurred after adult liver transplantation. However, vascular complications, such as postoperative thrombosis and anastomotic stenosis, are still common in the recipients undergoing living donor liver transplantation and split liver transplantation. Inappropriate treatment may lead to the loss of grafts and death of recipients. The authors have been engaged in liver transplantation for many years, witnessing persistent development of diagnostic and therapeutic technologies for vascular complications after liver transplantation. In this article, current status and development trend of diagnosis and treatment of different vascular complications were illustrated from the etiology, clinical manifestations, diagnosis and treatment of hepatic artery complications, portal vein complications, inferior vena cava and hepatic vein complications, aiming to further improve the survival rate of grafts and recipients and provide reference for promoting the development of clinical liver transplantation.
Expert Forum
Discussion on the indications and timing of targeted therapy and immunotherapy before and after liver transplantation for hepatocellular carcinoma
Li Keyue, Wei Guowei, Li Tao, Wang Chunlin, Tang Keli, Zhang Yi, Liu Yan
2022, 13(5): 561-568. doi: 10.3969/j.issn.1674-7445.2022.05.003
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Liver transplantation is one of the main treatments of early hepatocellular carcinoma (HCC). The recurrence of HCC after liver transplantation severely affects the long-term survival rate of the recipients. Targeted therapy and immunotherapy play a critical role in HCC downstaging, preventing disease progression, reducing recurrence rate, prolonging the survival and improving the quality of life. However, no consensus has been reached on the application of targeted therapy and immunotherapy in recipients undergoing liver transplantation for HCC, including indications, timing and dosage. In this article, clinical research progresses on the indications and timing of targeted therapy and immunotherapy before and after liver transplantation for HCC were reviewed, aiming to provide reference for prolonging the survival of recipients after liver transplantation for HCC.
Diagnosis and treatment of common biliary complications after orthotopic liver transplantation in adults
Hu Xinwen, Li Ting
2022, 13(5): 569-576. doi: 10.3969/j.issn.1674-7445.2022.05.004
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Liver transplantation has become an effective treatment for end-stage liver diseases. With rapid development of surgical techniques, donor selection, organ preservation and transportation, immunosuppressants and perioperative management, the overall incidence of complications after liver transplantation has been significantly decreased, whereas the incidence of biliary complications remains relatively high. At present, biliary complications after liver transplantation are still an important cause of graft failure. Nevertheless, the pathogenesis, diagnosis and treatment of biliary complications remain controversial, which are also research hotspots in the field of organ transplantation in recent years. In this article, new breakthrough and research progress upon biliary complications after orthotopic liver transplantation in adults were reviewed, aiming to provide theoretical basis for resolving biliary complications-related clinical issues.
Perioperative management of split liver transplantation
Li Chuan, Lai Yanhua
2022, 13(5): 577-582. doi: 10.3969/j.issn.1674-7445.2022.05.005
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In the context of shortage of donor livers, split liver transplantation has achieved the goal of "one donor liver for two recipients", which effectively alleviates the shortage of donor livers and has promising development prospect. With the advancement of liver transplant techniques, split liver transplantation may yield clinical prognosis equivalent to total liver transplantation. However, perioperative management of split liver transplantation still encounters multiple challenges, with demanding techniques requirement and high-risk postoperative complications. Besides, there is a possibility of dividing one high-quality donor liver into two marginal donor livers, which will affect the development of liver transplantation. In this article, perioperative management of split liver transplantation was discussed from the perspectives of preoperative evaluation, recipient management and postoperative complication management, aiming to provide reference for promoting the development of split liver transplantation and enhancing clinical prognosis of recipients after split liver transplantation.
Recurrence of IgA nephropathy after kidney transplantation
Zhang Yinsheng, Peng Xingtong, Yang Tingkai, Xing Jiali, Wen Jin, Ji Zhigang
2022, 13(5): 583-590. doi: 10.3969/j.issn.1674-7445.2022.05.006
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IgA nephropathy (IgAN) is one of the common primary glomerulonephritis, which is also an important risk factor for end-stage renal disease. Kidney transplantation is the optimal treatment for end-stage renal disease induced by IgAN, whereas there is still a risk of recurrence of IgAN after kidney transplantation. At present, research progress upon IgAN recurrence after kidney transplantation is relatively lacking. The pathogenesis of IgAN recurrence remains elusive, and its pathological manifestations are not specific. The diagnosis of IgAN recurrence still depends on renal biopsy. Besides, no effective prevention and treatment are available for recurrent IgAN. In this article, research progress on IgAN recurrence after kidney transplantation was illustrated from the perspectives of pathogenesis, diagnosis, risk factors and treatment, aiming to provide reference for clinical prevention and treatment of IgAN recurrence after kidney transplantation and improve clinical prognosis of kidney transplant recipients.
Research progress on the role of STING signal pathway in ischemia-reperfusion injury
Hu Haoran, Xu Jian, Zhou Haoming
2022, 13(5): 591-596. doi: 10.3969/j.issn.1674-7445.2022.05.007
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Ischemia-reperfusion injury (IRI) is a pathophysiological process, which widely exists in organ transplantation and surgery. IRI is mainly manifested with hypoxia injury of organs or tissues during the ischemia period, which could be further aggravated after reperfusion. Ischemia-reperfusion induces tissue cell injury, releases damage-associated molecular pattern and further activates multiple immune cells via pattern recognition receptor, leading to aseptic inflammation and aggravating tissue injury. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), as a critical member of pattern recognition receptor, could activate the stimulator of interferon genes (STING) signal pathway and play an important regulatory role in innate immune response. At present, increasing evidences have shown that cGAS-STING signal pathway plays a significant role in organ IRI. In this article, STING signaling pathway, its role and mechanism in IRI of different organs were reviewed, aiming to provide novel ideas for clinical interventions.
Original Article
Comprehensive minimally invasive treatment for biliary anastomotic stenosis after orthotopic liver transplantation: a single center analysis of 60 cases
Tian Wenjie, Dong Dinghui, Hao Jie, Tao Jie, Yang Xue, Tian Min, Liu Xuemin, Wang Bo, Sun Hao, Lyu Yi, Li Yu
2022, 13(5): 597-604. doi: 10.3969/j.issn.1674-7445.2022.05.008
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  Objective  To evaluate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP)-based comprehensive minimally invasive treatment for biliary anastomotic stenosis (BAS) after liver transplantation.  Methods  Clinical data of 60 BAS recipients after liver transplantation were retrospectively analyzed, 54 male and 6 female, aged (48±10) years. ERCP was initially carried out. If it succeeded, plastic or metallic stents were placed into the biliary tract. If it failed, percutaneous transhepatic cholangial drainage (PTCD) or single-operator cholangioscopy (SpyGlass) was adopted to pass through the stenosis. If all these procedures failed, magnetic anastomosis or other special methods were delivered. The incidence and treatment of BAS after liver transplantation were summarized. The efficacy, stent removal and recurrence were observed.  Results  The median time of incidence of BAS after liver transplantation was 8 (4, 13) months. Within postoperative 1 year, 1-2 years and over 2 years, 39, 16 and 5 recipients were diagnosed with BAS, respectively. All 60 BAS recipients after liver transplantation were successfully treated, including 56 cases initially receiving ERCP, and 41 completing BAS treatment, with a success rate of 73%. The failure of guide wire was the main cause of ERCP failure. The success rates of PTCD, SpyGlass and magnetic anastomosis were 5/9, 5/7 and 7/8, respectively. Two recipients were successfully treated by percutaneous choledochoscope-assisted blunt guide wire technique and stent placement in the biliary and duodenal fistula. After 3 (3, 4) cycles of ERCP and 13 (8, 18) months of stent indwelling, 38 recipients reached the stent removal criteria, including 25 plastic stents and 13 metallic stents. The indwelling time of plastic stents was longer than that of metallic stents (P < 0.05). Six cases suffered from stenosis recurrence at 12 (8, 33) months after stent removal, and the recurrence rate was 16%. Six patients were treated with ERCP, and 5 of them did not recur after the stents were successfully removed. Multivariate analysis showed that delayed diagnosis of stenosis and frequent ERCP before stent removal were the independent risk factors for BAS recurrence (both P < 0.05).  Conclusions  ERCP-based comprehensive minimally invasive treatment may improve the success rate of BAS treatment after liver transplantation and yield satisfactory long-term efficacy. Delayed diagnosis of BAS and high frequent ERCP required for stent removal are the independent risk factors for BAS recurrence.
Liver transplantation for acute liver failure in children: 8-year experience in a single center
Liu Ying, Sun Liying, Zhu Zhijun, Wei Lin, Qu Wei, Zeng Zhigui
2022, 13(5): 605-610. doi: 10.3969/j.issn.1674-7445.2022.05.009
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  Objective  To evaluate the efficacy of liver transplantation for acute liver failure (ALF) in children.  Methods  Clinical data of 15 children with ALF who underwent liver transplantation were collected and retrospectively analyzed. The proportion of ALF among children undergoing liver transplantation during the same period was calculated. The characteristics, postoperative complications and clinical prognosis of ALF children receiving liver transplantation were analyzed.  Results  In the same period, the proportion of ALF was 2.0% (15/743) among pediatric recipients undergoing liver transplantation. All 15 children had acute onset of ALF, and most of them were accompanied by fever, diarrhea and progressive yellowing of skin and sclera. Thirteen children were complicated with hepatic encephalopathy before operation (6 cases of stage Ⅳ hepatic encephalopathy), and two children were complicated with myelosuppression and granulocytopenia before liver transplantation. Ten children underwent living donor liver transplantation with relative donor liver, 4 received liver transplantation from donation after cardiac death (DCD), and 1 underwent Domino donor-auxiliary liver transplantation. Of 15 children, 12 recipients had the same blood type with their donors, 1 recipient had compatible blood type with the donor and 2 cases had different blood type with their donors. Among 15 children, 10 cases developed postoperative complications. Postoperative cerebral edema occurred in 5 cases, of whom 4 cases died of diffuse cerebral edema, and the remaining case was in a persistent vegetative state (eyes-open coma). Postoperative cytomegalovirus (CMV) infection was seen in 5 cases. Two children presented with aplastic anemia and survived after bone marrow transplantation, 1 case died of CMV hepatitis and viral encephalitis, and 2 cases died of diffuse brain edema. One child developed graft-versus-host disease (GVHD) after liver transplantation, and died of septic shock after bone marrow transplantation. Nine children survived and obtained favorable liver function during postoperative follow-up.  Conclusions  Liver transplantation is an efficacious treatment for ALF in children, which may enhance the survival rate. Brain edema is the main cause of death in ALF children following liver transplantation, and treatment such as lowering intracranial pressure, improving brain metabolism and blood purification should be actively performed. Liver transplantation should be promptly performed prior to the incidence of irreversible neurological damage in ALF children, which might prolong the survival and enhance long-term prognosis.
Predictive values of ALBI and EZ-ALBI scores for early survival of recipients with liver failure after liver transplantation
Yang Chengkai, Xu Jiamian, Wang Huaxiang, Lyu Lizhi, Jiang Yi, Wu Aiping
2022, 13(5): 611-617. doi: 10.3969/j.issn.1674-7445.2022.05.010
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  Objective  To evaluate the predictive values of albumin-bilirubin (ALBI) and easy albumin-bilirubin (EZ-ALBI) scores for early survival (postoperative 3 months) of recipients with liver failure after liver transplantation.  Methods  Clinical data of 137 recipients diagnosed with liver failure and underwent liver transplantation were retrospectively analyzed. The optimal cut-off values of preoperative ALBI, EZ-ALBI and MELD scores to predict early survival of recipients with liver failure after liver transplantation were determined by the area under the receiver operating characteristic (ROC) curve. The risk factors of early death of recipients with liver failure after liver transplantation were identified by univariate and multivariate Cox regression analyses. The effects of different ALBI and EZ-ALBI levels upon early prognosis of recipients with liver failure after liver transplantation were analyzed.  Results  The optimal cut-off values of ALBI, EZ-ALBI and MELD scores were 0.21, -19.83 and 24.36, and the AUC was 0.706, 0.697 and 0.686, respectively. Univariate Cox regression analysis showed that preoperative alanine aminotransferase(ALT)≥50 U/L, aspartate aminotransferase(AST)≥60 U/L, ALBI score≥0.21 and EZ-ALBI score≥-19.83 were the risk factors for early postoperative death of recipients with liver failure after liver transplantation (all P < 0.05). Multivariate Cox regression analysis demonstrated that preoperative ALBI score≥0.21 was an independent risk factor for early postoperative death of recipients with liver failure after liver transplantation (P < 0.05). According to the optimal cut-off value of ALBI score, the early survival rates in the ALBI < 0.21 (n=46) and ALBI≥0.21(n=91) groups were 93.5% and 64.8%, and the difference was statistically significant (P < 0.05). According to the optimal cut-off value of EZ-ALBI score, the early survival rates in the EZ-ALBI < -19.83(n=60) and EZ-ALBI≥-19.83(n=77) groups were 88.3% and 63.6%, and the difference was statistically significant (P < 0.05).  Conclusions  Preoperative ALBI score is of high predictive value for early survival of recipients with liver failure after liver transplantation, which could be utilized as a reference parameter for selecting liver transplant recipients.
Nicotinamide mononucleotide attenuates ischemia-reperfusion injury induced by donor liver from cardiac death through Sirt3
Jia Zhixing, Cheng Ying, Li Huiyuan, Jia Degong
2022, 13(5): 618-625. doi: 10.3969/j.issn.1674-7445.2022.05.011
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  Objective  To evaluate the effect and mechanism of nicotinamide mononucleotide (NMN) on ischemia-reperfusion injury (IRI) induced by donor liver after cardiac death in rat models.  Methods  Rat models of orthotopic liver transplantation were established by "magnetic ring + double cuff" method. SD rats were randomly divided into the sham operation group (Sham group), orthotopic liver transplantation group (OLT group), NMN treatment + orthotopic liver transplantation group (NMN group), NMN+sirtuin-3 (Sirt3) inhibitor (3-TYP) + orthotopic liver transplantation group (NMN+3-TYP group), respectively. Pathological changes and hepatocyte apoptosis of the rats were observed in each group. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in liver tissues were detected. The expression levels of Sirt3, microtubule-associated protein 1 light chain 3 (LC3)Ⅱ, PTEN-induced putative kinase 1 (PINK1), Parkin and translocase of the outer mitochondrial membrane 20 (TOMM20) in liver tissues were measured. Postoperative survival of the rats in each group was analyzed.  Results  Compared with the Sham group, serum ALT and AST levels were higher in the OLT group. Compared with the OLT group, the levels of ALT and AST were decreased in the NMN group. Compared with the NMN group, the levels of ALT and AST were increased in the NMN +3-TYP group (all P < 0.05). The liver tissue structure of rats in the Sham group was basically normal. In the OLT group, pathological changes, such as evident congestion, vacuolar degeneration and hepatocyte necrosis, were observed in the liver tissues. Compared with the Sham group, Suzuki score and apoptosis rate were higher in the OLT group. Suzuki score and apoptosis rate in the NMN group were lower than those in the OLT group. Suzuki score and apoptosis rate in the NMN+3-TYP group were higher compared with those in the NMN group (all P < 0.05). Compared with the Sham group, the SOD content was decreased, whereas the MDA content was increased in the OLT group. Compared with the OLT group, the SOD content was increased, whereas the MDA content was decreased in the NMN group. Compared with the NMN group, the SOD content was decreased, whereas the MDA content was increased in the NMN+3-TYP group (all P < 0.05). Compared with the Sham group, the relative expression levels of Sirt3 and TOMM20 proteins were down-regulated, whereas those of PINK1, Parkin and LC3Ⅱproteins were up-regulated in the OLT group. Compared with the OLT group, the relative expression levels of Sirt3, PINK1, Parkin and LC3Ⅱproteins were up-regulated, whereas that of TOMM20 protein was down-regulated in the NMN group. Compared with the NMN group, the relative expression levels of PINK1, Parkin and LC3Ⅱproteins were down-regulated, whereas that of TOMM20 protein was up-regulated in the NMN+3-TYP group (all P < 0.05). In the Sham group, the 7 d survival rate of rats was 100%, 50% in the OLT group, 75% in the NMN group and 58% in the NMN+3-TYP group, respectively.  Conclusions  NMN may enhance the antioxidative capacity of the liver, induce PINK1/Parkin-mediated mitochondrial autophagy, and alleviate IRI of the liver by up-regulating Sirt3, thereby playing a protective role in the donor liver after cardiac death.
Effect and mechanism of terminal fucosylation inhibitor on ciclosporin-induced renal epithelial-mesenchymal transition
Mao Kaifeng, Luo Jialiang, Lin Fenwang, Zuo Daming, Ye Junsheng
2022, 13(5): 626-633. doi: 10.3969/j.issn.1674-7445.2022.05.012
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  Objective  To evaluate the effect and mechanism of terminal fucosylation inhibitor 2-deoxy-D-galactose (2-D-gal) on ciclosporin (CsA)-induced renal epithelial-mesenchymal transition (EMT).  Methods  Fifteen male C57BL/6 mice aged 8-10 weeks were randomly and evenly divided into the control group (Ctrl group), CsA group and CsA+2-D-gal group (n=5). The expression levels of fucosyltransferase 1 (FUT1), EMT-associated proteins including E-cadherin, Vimentin, α-smooth muscle actin (α-SMA) in the kidney tissues of the Ctrl and CsA groups were detected by Western blot. The expression levels of terminal fucose in the kidney tissues of Ctrl and CsA groups were determined by immunofluorescence. The renal fibrosis of mice in each group was evaluated by Masson staining. The blood urea nitrogen and serum creatinine levels of mice in each group were detected. The in vitro EMT model of renal tubular epithelial cell HK2 was induced by CsA. HK2 cells were stimulated with 0, 2.5, 5.0 and 10.0 μmol/L CsA for 24 h, respectively. In addition, HK2 cells were divided into the Ctrl, 2-D-gal, CsA and CsA+2-D-gal groups. The morphology of HK2 cells after stimulation with different concentrations of CsA and in each group was observed. The expression levels of FUT1, E-cadherin, Vimentin and α-SMA in HK2 cells after stimulation with different concentrations of CsA and in each group were detected by Western blot. The expression level of terminal fucose in HK2 cells of the Ctrl and CsA groups was measured by immunofluorescence.  Results  Compared with the Ctrl group, the relative expression of E-cadherin protein was down-regulated, those of FUT1, Vimentin and α-SMA proteins were up-regulated (all P < 0.05), and that of terminal fucose in the mouse kidney tissues was up-regulated in the CsA group. Compared with the Ctrl group, the blood urea nitrogen and serum creatinine levels in the CsA and CsA+2-D-gal groups were up-regulated (all P < 0.05). Compared with the CsA group, the blood urea nitrogen and serum creatinine levels in the CsA+2-D-gal group were down-regulated (both P < 0.05). Compared with the Ctrl group, the collagen fiber deposition was increased and the relative expression of α-SMA protein was up-regulated in the mouse kidney tissues of CsA and CsA+2-D-gal groups (all P < 0.05). Compared with the CsA group, the collagen fiber deposition was decreased and the relative expression of α-SMA protein in the mouse kidney tissues was down-regulated in the CsA+2-D-gal group (both P < 0.05). With the increase of CsA concentration, the morphology of HK2 cells gradually became longer and thinner from original normal cobblestone shape, the relative expression levels of FUT1, Vimentin and α-SMA protein in HK2 cells were up-regulated, and that of E-cadherin protein was down-regulated in a concentration-dependent manner. Compared with the Ctrl group, the expression level of terminal fucose of HK2 cells was up-regulated in the CsA group. After CsA treatment combined with 2-D-gal intervention, the morphology of HK2 cells in the CsA+2-D-gal group was restored to resemble that of normal HK2 cells. Compared with the CsA group, the relative expression of E-cadherin protein in HK2 cells was up-regulated, whereas those of Vimentin and α-SMA proteins were down-regulated in the CsA+2-D-gal group (all P < 0.05).  Conclusions  CsA may induce EMT both in vivo and in vitro, and the terminal fucosylation is increased. 2-D-gal may inhibit CsA-induced EMT by suppressing the terminal fucosylation.
A modified mouse model of orthotopic left lung transplantation based on "pendulum" anastomosis of the reverse-view plane (with video demonstration)
Li Caihan, Huang Heng, Wang Junjie, Tang Hongtao, Wu Ye, Hou Senlin, Liu Peizhi, Yang Wan, Chen Tingting, Zhang Shengxuan, Fu Siyi, Zuo Yujie, Yang Junjie, Yan Haoji, Tian Dong
2022, 13(5): 634-639. doi: 10.3969/j.issn.1674-7445.2022.05.013
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  Objective  To modify the mouse model of orthotopic left lung transplantation from different perspectives, aiming to establish a simpler, faster and stabler mouse model of lung transplantation.  Methods  Based on preliminary modified rat model of orthotopic left lung transplantation established by our team, varying extent of modifications were made regarding the tracheal intubation, cannula preparation and anastomosis procedures of orthotopic left lung transplantation in the recipient mice. Orthotopic left lung transplantation in 40 mice were performed by an operator with microsurgical experience. The dissection of the recipient's hilar structure was carried out at the plane of the hilar clamp model within the reverse-view, and the three branches (left main bronchus, pulmonary artery and pulmonary vein) of the pulmonary hilum were anastomosed in turn by the "pendulum" anastomosis method. The operation time of each procedure was recorded. The recipient mice were sacrificed at postoperative 2 weeks, and the incidence of postoperative complications was recorded.  Results  Lung transplantation was successfully completed in 40 mice, with no bronchial and vascular tearing or twisting, and no bleeding at the anastomosis site. The overall cardiopulmonary procurement time was (10.7±1.5) min, cannula preparation time was (16.2±1.5) min, cold ischemia time was (25.1±2.4) min, warm ischemia time was (19.4±1.6) min, and the total operation time was (57.2±2.9) min, respectively. During the follow-up from 6 to 14 days after surgery, one recipient mouse died of pleural effusion, probably caused by infection. No pneumothorax, thrombosis or atelectasis was found in the remaining recipient mice during postoperative follow-up.  Conclusions  The modified mouse model of orthotopic left lung transplantation based on "pendulum" anastomosis of the reverse-view plane possesses multiple advantages of short operation time, high success rate and few complications, which is expected to become an alternative model of studying pathological changes after lung transplantation and worthy of further application.
Diagnosis and treatment of Takotsubo syndrome after liver transplantation and literature review
Kang Yisheng, Li Danyang, Yu Lixin, Xie Yan, Liu Yihe
2022, 13(5): 640-646. doi: 10.3969/j.issn.1674-7445.2022.05.014
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  Objective  To summarize the experience of diagnosis and treatment of Takotsubo syndrome (TTS) after liver transplantation.  Methods  Clinical data of one TTS patient after liver transplantation was retrospectively analyzed. Clinical features, diagnosis and treatment strategies were summarized, and literature review was conducted.  Results  A 43-year-old female patient successfully underwent split liver transplantation due to primary biliary cirrhosis for 8 years. At postoperative 3 d, the patient developed anxiety, irritation, dyspnea, disorientation, hypotension, N-terminal pro-brain natriuretic peptide (NT-proBNP) of > 35 000 pg/mL, creatine kinase isoenzyme (CK-MB) of 5.9 U/L and troponin I (TnI) of 1.78 μg/L. Electrocardiogram indicated the signs of sinus rhythm. Echocardiography indicated diffuse weakening of the left ventricular wall motion and spherical dilatation of the apex, accompanied with moderate and severe regurgitation of the mitral valve and tricuspid valve. The left ventricular ejection fraction (LVEF) declined to 23%, whereas no abnormal segmental motion of ventricular wall or corresponding electrocardiogram changes were observed. The possibility of acute coronary syndrome was excluded. The InterTAK diagnostic score was 73. The diagnosis of TTS after liver transplantation was considered. Metoprolol, coenzyme Q10, recombinant human brain natriuretic peptide, deacetyl lanatoside and lorazepam were given. Echocardiography at postoperative 10 d showed that the left ventricular function was significantly improved and the LVEF recovered to 50%. The patient was discharged 40 d after liver transplantation. The liver function was recovered well. During postoperative follow-up, she was given with metoprolol till the submission date, and no recurrence was reported.  Conclusions  TTS after liver transplantation is rare in clinical practice. It is difficult to make the diagnosis. The condition of TTS is severe and clinical prognosis is poor. Prompt diagnosis and interventions should be implemented.
Review Article
Research progress on the role of programmed cell death in hepatic ischemia-reperfusion injury
Bai Yang, Shi Jihua, Zhang Shuijun
2022, 13(5): 647-652. doi: 10.3969/j.issn.1674-7445.2022.05.015
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Liver transplantation is an effective treatment for the end-stage liver disease. However, hepatic ischemia-reperfusion injury (HIRI) will inevitably occur during liver transplantation, which might lead to early graft dysfunction or aggravate rejection. The underlying protective mechanism remains to be further elucidated. Programmed cell death is an important mechanism of HIRI, and multiple novel types of programmed cell death participate in the pathological process of HIRI. In-depth study of programmed cell death is expected to further improve the therapeutic effect of liver transplantation. In this article, research progresses on apoptosis, autophagy and autophagy-dependent cell death, ferroptosis, necroptosis, pyroptosis, pathanatos and other common programmed cell death patterns in HIRI were reviewed, aiming to provide reference for enhancing the success rate of liver transplantation and improving clinical prognosis of the recipients.
Application progress of ischemic preconditioning in ischemia-reperfusion injury of renal allografts
Shi Lang, Zhu Jiefu, Wu Xiongfei
2022, 13(5): 653-658. doi: 10.3969/j.issn.1674-7445.2022.05.016
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Kidney transplantation is more efficacious compared with other organ transplantations. Nevertheless, postoperative complications, such as renal ischemia-reperfusion injury (IRI), severely affect the survival rate and quality of life of recipients. How to mitigate the IRI of renal allografts has become one of the key topics in the field of kidney transplantation. At present, ischemic preconditioning enables renal allografts to adapt to ischemia, which is one of the effective methods to prevent the progression of IRI. However, the underlying mechanism remains elusive. In this article, the application of ischemic preconditioning in IRI, the regulation mechanism of ischemic preconditioning on the IRI of renal allografts at the cellular level and intracellular signaling pathway, and clinical application value and prospect of ischemic preconditioning were reviewed, aiming to provide reference for alleviating the IRI of renal allografts, enhancing the survival rate of the recipients and renal allografts and improving the quality of life of recipients.
Research progress on the role of transient receptor potential canonical 6 in ischemia-reperfusion injury
Guo Wenwen, Yuan Yuan, Wei Huafeng, Luo Hao, Li Lingyu, Lyu Xinghua
2022, 13(5): 659-665. doi: 10.3969/j.issn.1674-7445.2022.05.017
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Ischemia-reperfusion injury (IRI) refers to the reperfusion injury caused by the recovery of blood supply of ischemic tissues or organs, which commonly occurs in organ transplantation and other surgical procedures. IRI may cause a series of severe clinical issues, such as delayed graft function, acute kidney injury, myocardial infarction, ischemic stroke and circulatory arrest, etc. These events yield high incidence and fatality. At present, no effective solution has been available. Transient receptor potential canonical 6 (TRPC6), a member of Ca2+ channel family, is highly expressed in multiple types of cells. It may adjust many physiological functions by regulating intracellular Ca2+ concentration, which has become an important target for developing therapeutic drugs for multiple diseases. In this article, research progresses on the introduction and function of TRPC6, the association between TRPC6 and IRI and the therapeutic prospect of TRPC6 targeted drugs in IRI were reviewed, aiming to provide novel insights into the prevention and treatment of IRI during organ transplantation
Research progress on the role of miR-155 in rejection of organ transplantation
Zhang Yang, Yang Jinwei, Li Xingde, Ma Xuejiao, Zhang Hanshu, Song Cangsang
2022, 13(5): 666-671. doi: 10.3969/j.issn.1674-7445.2022.05.018
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Abstract:
Rejection has constantly been an unresolved challenge in the field of organ transplantation. The research on the mechanism of rejection plays a significant role in improving the efficacy of organ transplantation and enhancing the survival rate of graft. The innate and specific immune responses of the human body jointly participate in the graft rejection, leading to graft injury. In recent years, multiple researchers have conducted in-depth studies on the mechanism underlying the role of microRNA (miR) in regulating rejection. Among them, miR-155 has been widely considered as a key factor involved in immune regulation. The expression level and functional status of miR-155 may be intimately associated with the occurrence of rejection, which may become a new target for overcoming rejection. In this article, relevant studies on the role of miR-155 in regulating key immune cells in innate and specific immune responses were reviewed, aiming to provide novel ideas for the development of new immunosuppressants and rejection therapy.
Imaging manifestations of central nervous system complications after heart transplantation
Fu Xiaona, Zhang Li, Wang Jing
2022, 13(5): 672-677. doi: 10.3969/j.issn.1674-7445.2022.05.019
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Abstract:
Heart transplantation is the main treatment of end-stage heart failure. With the advancement of heart transplantation and rational use of postoperative immunosuppressants, the survival rate of recipients has been gradually enhanced. However, a variety of central nervous system complications may still occur following heart transplantation, including immunosuppressant-associated neurotoxicity, epilepsy, stroke, encephalopathy, central nervous system infection and de novo malignant tumors in the central nervous system. These complications will severely affect the quality of life of heart transplant recipients. Consequently, prompt imaging diagnosis plays a significant role in the prevention and treatment of central nervous system complications. In this article, main imaging manifestations of central nervous system complications after heart transplantation were reviewed, aiming to provide reference for prompt diagnosis and differential diagnosis of complications, guide clinical treatment and management, and improve the long-term prognosis of the recipients.
Application of contrast-enhanced ultrasound in evaluation of donor kidney quality
Dong Shangxin, Shi Huibo, Zhao Yuanyuan, Li Kaiyan, Luo Hongchang, Zhang Bo, Chen Zhishui, Jiang Jipin
2022, 13(5): 678-682. doi: 10.3969/j.issn.1674-7445.2022.05.020
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Abstract:
In recent years, although the quantity of organ donation after citizen's death has been constantly increased, a large number of patients with end-stage renal diseases are waiting for kidney transplantation every year. The imbalance between donor and recipient is still one of the main problems affecting kidney transplantation in clinical practice. Therefore, it is of clinical significance to accurately evaluate the quality of donor kidney and fully utilize the expanded criteria donor kidney. Contrast-enhanced ultrasound has been gradually applied in the detection of multiple solid organs due to its safety, portability, real-time detection, quantification and other characteristics, and it also has promising application prospect in the evaluation of donor kidney quality. In this article, the advantages and limitations of current evaluation methods for donor kidney and current status and advantages of contrast-enhanced ultrasound in donor kidney evaluation were reviewed, and the application prospect of contrast-enhanced ultrasound in the evaluation of donor kidney quality was discussed, aiming to increase the methods and enhance the accuracy for donor kidney evaluation, and provide reference for rational use of expanded criteria donor kidney.