器官移植

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Editorial

Xenotransplantation rejection and preventive and therapeutic strategies

He Xiaozhou, Fu Jiazhao, Zhou Cuixing

, Available online , doi: 10.3969/j.issn.1674-7445.2024079

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Xenotransplantation is a potential solution to the shortage of human organs. In the previous 100 years, xenotransplantation has witnessed preliminary attempts and persistent progress. At present, it has entered a new stage of rapid development and achieved a series of results. Nevertheless, the management of xenotransplantation rejection is more challenging compared with that of allogeneic organ transplantation rejection. Therefore, researchers have developed a series of immunosuppressive strategies, such as use of genetically modified pig donors, use of traditional and novel immunosuppressants, and co-transplantation of donor pig thymus with donor organs, aiming to adjust the immune system response of recipients, mitigate the intensity of rejection and prolong the survival time of grafts. In this article, research progress in the mechanism, prevention and treatment strategies of xenotransplantation rejection was reviewed, aiming to provide reference for accelerating subsequent development of xenotransplantation.

Review Article

Research progress on the role of normothermic machine perfusion in the preservation of severed limbs

Jia Zhibo, Guan Yanjun, Song Xiangyu, Dong Yanghui, Yang Boyao, Cui Mengyi, Xu Wenjing, Peng Jiang

, Available online , doi: 10.3969/j.issn.1674-7445.2024062

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Limb dismemberment injuries are common in clinical practice, and safe and effective protection of the dismembered limb is the key to successful limb replantation. Normothermic machine perfusion has made significant breakthrough in the field of organ transplantation, which may maintain the active function of organs and tissues for a long period of time and prolong the preservation time. These findings have been validated in large animal models and clinical trials. Meantime, this technology is expected to provide novel reference for the preservation and functional recovery of severed limbs. Therefore, this paper reviews the problems of static cold preservation in the preservation of disarticulated limbs, the development history of mechanical perfusion, the current status of clinical application of ambient mechanical perfusion of disarticulated limbs as well as the problems to be solved, and looks forward to the direction of its development and the prospect of its clinical application, with a view to promoting the wide application of this technology in the clinic.

Original Article

Single cell sequencing reveals the antigen presentation characteristics of dendritic cells and B cells in cardiac grafts

Zhu Yuexing, Chen Chao, Xu Ye, Fan Yuxi, Zheng Xinguo, Luo Qiulin, Tang Zhouqi, Zhang Hedong, Li Tengfang, Peng Longkai, Dai Helong

, Available online , doi: 10.3969/j.issn.1674-7445.2024115

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Objective To investigate the antigen presentation characteristics of dendritic cells (DC) and B cells in cardiac grafts. Methods The heart of BALB/c mice was transplanted into the abdominal cavity of C57BL/6J mice. CD45⁺ cells in the heart graft were extracted and sorted by flow cytometry at postoperative 5 d, and single cell RNA sequencing was performed. Taking DC and B cell subsets in cardiac grafts as the main study cells, the changing trend, antigen presenting ability and intercellular communication with T cells after heart transplantation were analyzed by bioinformatics analysis and flow cytometry. Gene ontology (GO) function enrichment difference analysis was adopted to prove the specific function and the reliability annotation of cell subsets. Results Germinal center-like B cell (GC-L B) was the B cell subset with the largest increase in quantity during the acute rejection phase, accounting for 87%. Classical DC (cDC) 2 was the only DC subset with a significant increase in quantity during acute rejection of heart transplantation, accounting for 44% of DC subset, and it occupied the highest communication intensity with T cells after heart transplantation. Mononucleated DC (moDC) and memory B cell (MBC) were the main transmitters of T cell input signals non-transplanted hearts, whereas transformed into cDC2 and GC-L B during the acute rejection phase. Among them, MBC and GC-L B were the main sources of T cell input signals in non-transplanted hearts and heart grafts. Conclusions Compared with DC, B cells occupy a higher number and weight in the intercellular communication with T cells before and after heart transplantation, prompting that the antigen presenting activity of B cells is more active and stronger than DC in the early stage of acute rejection of heart transplantation.

Clinical analysis of early Klebsiella pneumoniae infection after liver transplantation

Zheng Kezhong, Chen Song, He Zhixiang, Wang Guobin, Zhao Hongchuan, Geng Xiaoping, Huang Fan

, Available online , doi: 10.3969/j.issn.1674-7445.2024053

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To identify early Klebsiella pneumoniae (KP) infection after liver transplantation and its impact on prognosis. Methods Clinical data of 171 liver transplant recipients were retrospectively analyzed, and they were divided into the non-infection (n=52) and infection groups (n=119) according to the bacterial culture results at postoperative 2 weeks. In the infection group, KP was not detected in 86 cases (non-KP infection group), and KP was cultured in 33 cases (KP infection group). Preoperative, intraoperative and postoperative data were statistically compared between the non-infection and infection groups, and between the non-KP infection and KP infection groups. The risk factors of early KP infection after liver transplantation and the influencing factors of long-term survival of the recipients were analyzed. Results Compared with the non-infection group, model for end-stage liver disease (MELD) score and total bilirubin level were higher, the operation time was longer, the length of postoperative intensive care unit (ICU) stay and the length of hospital stay were longer, the amount of intraoperative red blood cell transfusion was higher, the hospitalization expense was higher, the incidence of severe complications was higher, white blood cell count, absolute neutrophil cell count and neutrophil-to-lymphocyte ratio at postoperative 14 and 30 d were higher, absolute lymphocyte count at postoperative 14 d was lower and hemoglobin level at postoperative 30 d was lower in the infection group. The differences were statistically significant (all P<0.05). Compared with the non-KP infection group, MELD score, total bilirubin level and aspartate aminotransferase (AST) level were higher, the operation time and the length of postoperative ICU stay were longer, the hospitalization expense was higher, the 90-d fatality was higher, the albumin level at postoperative 14 d was lower, and total bilirubin level at postoperative 30 d was higher in the KP infection group. The differences were statistically significant (all P<0.05). Among 33 recipients with KP infection, 16 cases were resistant to carbapenem antibiotics, and 7 of them died within postoperative 90 d. Seventeen cases were intermediate or sensitive to carbapenem antibiotics, and 4 of them died within postoperative 90 d. Preoperative MELD score ≥17 and operation time＞415 min were the independent risk factors for KP infection after liver transplantation (both P<0.05). The length of postoperative ICU stay ≥44 h and KP infection were the independent risk factors for long-term prognosis of liver transplantation (both P<0.05). Conclusions KP infection is an independent risk factor for death after liver transplantation. High preoperative MELD score and long operation time are the independent risk factors for early KP infection after liver transplantation.

Guidelines for clinical diagnosis and treatment of delayed graft function in kidney transplant recipients in China

Branch of Organ Transplantation of Chinese Medical Association, Branch of Kidney Transplantation of China International Exchange and Promotive Association for Medical and Health Care,

, Available online , doi: 10.3969/j.issn.1674-7445.2024156

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Delayed graft function in kidney transplant recipients is one of the common early complications after kidney transplantation, which is an independent risk factor affecting the short-term and long-term survival of renal allografts. Branch of Organ Transplantation of Chinese Medical Association and Branch of Kidney Transplantation of China International Exchange and Promotive Association for Medical and Health Care organized well-known Chinese experts in organ transplantation and related disciplines to formulate and discuss the determination of the scope and clinical problems, evidence retrieval and screening, and the formation of recommendations based on “Technical Specification for the Diagnosis and Treatment on Delayed Graft Function After Renal Transplantation (2019 edition)”. After two rounds of collective examination and approval by Chinese Medical Association and China International Exchange and Promotive Association for Medical and Health Care, “Guidelines for Clinical Diagnosis and Treatment of Delayed Graft Function in Kidney Transplant Recipients in China” was finally formulated. This guideline puts forward recommendations and explanations regarding 21 clinical problems including the concept, mechanism, risk factors, diagnosis, prevention, treatment and application of immunosuppressive drugs for delayed graft function in kidney transplant recipients, aiming to standardize the diagnosis, prevention and treatment of delayed graft function in kidney transplant recipients, enhance clinical efficacy of kidney transplantation, prolong short-term and long-term survival of kidney transplant recipients and renal allografts and promote the development of the discipline of transplantation.

, Available online

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Guideline and Consensus

Guidelines for clinical diagnosis and treatment of nontuberculous mycobacterial disease in kidney transplant recipients

, Available online , doi: 10.3969/j.issn.1674-7445.2024142

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In recent years, the infection of nontuberculous mycobacterium (NTM) has been increasing rapidly, which captivates widespread attention. The infection rate of NTM in kidney transplant recipients is more significantly elevated due to the impact of immunosuppressive drugs and other factors. However, due to the lack of sufficient research evidence, relevant guidelines for the diagnosis and treatment of NTM after kidney transplantation are still lacking. To further standardize the diagnosis and treatment of NTM disease in kidney transplant recipients, and deepen medical practitioners' understanding and diagnosis and treatment of NTM disease in organ transplantation in China, Branch of Organ Transplantation of Chinese Medical Association organized relevant experts to formulate this guideline by referring to the latest edition of “An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases”, “Expert Consensus on the Diagnosis and Treatment of Nontuberculous Mycobacterial Disease”, and “Technical Specification for Clinical Diagnosis and Treatment of Nontuberculous Mycobacteria in Organ Transplant Recipients (2019 Edition) ”, and considering the characteristics of kidney transplant recipients.

Guidelines for clinical diagnosis and treatment of urinary tract infection in kidney transplant recipients in China

Branch of Organ Transplantation of Chinese Medical Association,

, Available online , doi: 10.3969/j.issn.1674-7445.2024140

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Urinary tract infection is the most common infectious complication after kidney transplantation. To further reduce the incidence of urinary tract infection after kidney transplantation, improve the diagnosis and treatment level of urinary tract infection after kidney transplantation in China, prevent the development of bacterial drug resistance and ensure the safety and effectiveness of drug use, Branch of Organ Transplantation of Chinese Medical Association organized experts in the fields of kidney transplantation and infectious diseases to consider clinical status of urinary tract infection after kidney transplantation in China, refer to “Diagnosis and Treatment of Urological and Andrological Diseases in China (2022 edition)” and “Urinary Tract Infection in Solid Organ Transplant Recipients in American Society of Transplantation Practical Guidelines for Infectious Diseases (2019 edition) ”, and formulate “Guidelines for Clinical Diagnosis and Treatment of Urinary Tract Infection in Kidney Transplant Recipients in China” from the perspectives of clinical classification and definition, epidemiology and etiology, diagnosis and treatment of urinary tract infection after kidney transplantation, respectively.

Expert Forum

Exploratory road of liver xenotransplantation: from scientific research to clinical application

Li Xiao, Cao Weiwei, Yu Liang

, Available online , doi: 10.3969/j.issn.1674-7445.2024043

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With the advancement of surgical technologies and the improvement of perioperative management, the survival rates of organ transplant recipients and grafts have been significantly elevated. Shortage of donor organs has become the main obstacle to further development of organ transplantation. Recently, kidney and heart xenotransplantation with genetically modified pigs as donors have entered clinical trials and achieved favorable results. Xenotransplantation has repeatedly become a hot spot in biomedical research. Compared with heart and kidney, the survival time of liver grafts from genetically modified pigs in non-human primates is shorter. Besides, experimental results are dramatically different. Hence, it is not eligible for clinical trials. Consequently, recent research progress in xenotransplantation was reviewed from surgical pattern selection, coagulation dysfunction and acute vascular rejection, advances in liver xenotransplantation were summarized, and the main problems hindering xenotransplantation from entering clinical trials and potential solutions were illustrated, aiming to provide reference for xenotransplantation from scientific research to clinical application.