Xenotransplantation is an important approach to addressing the shortage of donor organs. However, it still faces numerous challenges, such as acute rejection and zoonotic diseases. Organoid-on-a-chip technology refers to a microcell culture device that simulates the physiological functions of human organs in vitro. In recent years, it has achieved a series of important results in the field of allotransplantation and has great application prospects in the field of xenotransplantation, bringing new opportunities for xenotransplantation research. Therefore, this article discusses the current research status and progress of organoid-on-a-chip technology, combined with the various problems faced by xenotransplantation, to explore the application of organoid-on-a-chip technology in solving the selection of immunosuppressive regimens, matching and viral reactivation in xenotransplantation. This aims to open up new avenues for solving the current problems in the field of xenotransplantation and promote its further development.

Objective To explore the public attitude towards kidney xenotransplantation in China by constructing and validating the prediction model based on xenotransplantation questionnaire. Methods A convenient sampling survey was conducted among the public in China with the platform of Wenjuanxing to analyze public acceptance of kidney xenotransplantation and influencing factors. Using random distribution method, all included questionnaires (n=2 280) were divided into the training and validation sets according to a ratio of 7:3. A prediction model was constructed and validated. Results A total of 2 280 questionnaires were included. The public acceptance rate of xenotransplantation was 71.3%. Multivariate analysis showed that gender, marital status, resident area, medical insurance coverage, religious belief, vegetarianism, awareness of kidney xenotransplantation and whether on the waiting list for kidney transplantation were the independent influencing factors for public acceptance of kidney xenotransplantation (all P<0.05). The area under the curve (AUC) of receiver operating characteristic (ROC) of the prediction model in the training set was 0.773, and 0.785 in the validation set. The calibration curves in the training and validation sets indicated that the prediction models yielded good prediction value. Decision curve analysis (DCA) suggested that the prediction efficiency of the model was high. Conclusions In China, public acceptance of kidney xenotransplantation is relatively high, whereas it remains to be significantly enhanced. The prediction model based on questionnaire survey has favorable prediction efficiency, which provides reference for subsequent research.

Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, organ shortage is a global problem, which limits further development of organ transplantation. Recent research shows that genetically modified pig may become a realistic alternative source of clinical organ transplantation donor. Xenotransplantation may serve as one of the effective measures to resolve the problem of organ shortage. Since 2021, 2 cases of living xenotransplantation and 6 cases of xenotransplantation in brain death recipients have been performed worldwide, and phase Ⅰ clinical trial of xenotransplantation has been launched, and the results have exceeded expectations. Therefore, in this article, recent clinical trial results of xenotransplantation in living and brain death recipients were retrospectively analyzed, and scientific, technical and ethical issues related to clinical research of xenotransplantation were illustrated, hoping to provide reference for clinical research of xenotransplantation in China and promote the development of xenotransplantation in clinical practice.

Objective To summarize the experience and practical value of living donor kidney harvesting in Bama miniature pigs with six gene modified. Methods The left kidney of Bama miniature pigs with six gene modified was obtained by living donor kidney harvesting technique. First, the ureter was occluded, and then the inferior vena cava and abdominal aorta were freed. During the harvesting process, the ureter, renal vein and renal artery were exposed and freed in sequence. The vascular forceps were used at the abdominal aorta and inferior vena cava, and the renal artery and vein were immediately perfused with 4℃ renal preservation solution, and stored in ice normal saline for subsequent transplantation. Simultaneously, the donor abdominal aorta and inferior vena cava gap were sutured. The operation time, blood loss, warm and cold ischemia time, postoperative complications and the survival of donors and recipients were recorded. Results The left kidney of the genetically modified pig was successfully harvested. Intraoperative bleeding was 5 mL, warm ischemia time was 45 s, and cold ischemia time was 2.5 h. Neither donor nor recipient pig received blood transfusion, and urinary function of the kidney transplanted into the recipient was recovered. The donor survived for more than 8 months after the left kidney was resected. Conclusions Living donor kidney harvesting is safe and reliable in genetically modified pigs. Branch blood vessels could be processed during kidney harvesting, which shortens the process of kidney repair and the time of cold ischemia. Living donor kidney harvesting contributes to subsequent survival of donors and other scientific researches.

Effective preoperative matching of organ transplantation is essential for the success of organ transplantation.The current methods of preoperative matching for xenotransplantation are derived from human allogeneic organ transplantation.However,these methods are simple and cannot accurately predict whether rejection will occur after transplantation.A noteworthy feature of xenotransplantation lies in the stability of the donor source and the clarity of its genotype,which facilitate convenient sampling and ensure robust repeatability.The multi-link and multi-dimensional preoperative matching is conducive to accurately screening suitable donors and reducing the occurrence of postoperative rejection after xenotransplantation,including making full use of the advantages of donor control in xenotransplantation,expanding tissue level matching methods on the basis of improving traditional cytological matching,paying attention to the role of endothelial cells in matching,and developing organic-level matching methods.Therefore,this article reviews the methods of allogeneic organ transplantation matching,current methods,existing problems and possible breakthroughs of xenotransplantation matching,in order to provide reference for further research on xenotransplantation matching.

Objective To analyze the research progress and development trend of xenotransplantation in China.Methods Literatures related to xenotransplantation in Chinese and English were searched from CNKI and Web of Science Core Collection databases from January 1,2014 to December 31,2023.Visualization analysis of the research progress,hot topics and research frontiers in this field was performed by CiteSpace software and R language from the aspects of number of publications,keywords,distribution of journal origin,core author cooperation network,main research institutions,and citation of key literatures,etc.Results Chinese scholars published 684 articles in Chinese and 624 articles in English,ranking 2nd worldwide.The top 3 Chinese journals regarding the number of publications were Organ Transplantation,Practical Journal of Organ Transplantation(Electronic Version)and Acta Laboratorium Animalis Scientia Sinica.The top 3 English journals were Xenotransplantation,Frontiers in Immunology and Scientific Reports.The top 5 authors regarding the number of publications in Chinese were Pan Dengke,Cai Zhiming,Mou Lisha,Li Xiao and Dou Kefeng.The top 5 authors regarding the number of publications in English were Mou Lisha,Cai Zhiming,Dai Yifan,Wang Yi and Pan Dengke.High-frequency Chinese keywords included xenotransplantation,immune rejection,transplantation,xenogenic,animal model,xenogeneic bone,liver transplantation,gene editing,kidney transplantation,burn and bone transplantation.High-frequency English keywords were expression,xenotransplantation,cells,transplantation and survival.Conclusions In recent years,certain research achievement and global influence have been obtained in the field of xenotransplantation in China,involving a variety of disciplines and a wide range of research contents.However,cooperation among different institutions is still lacking.In the future,cross-regional and interdisciplinary communication and cooperation should be prompted.Resource sharing and integration should be strengthened to maintain rapid and steady advancement in this field.

Organ shortage is a critical factor limiting the development of organ transplantation. Xenotransplantation is expected to resolve the problem of organ shortage, which has become a new research hotspot. Study of costimulatory signaling pathway related to T cell regulation is a hot topic in terms of immunity of xenotransplantation. Since the discovery of costimulatory molecule CD28, multiple costimulatory molecules have been identified, including costimulatory and coinhibitory receptors and their related ligands. Specific T cell activation of donors is the key factor leading to acute immune rejection. The expression and induction of costimulatory molecules on T cells differ during different immune stages, and these costimulatory molecules play a key role in maintaining T cell tolerance and the balance of T cell immune response. At present, increasing attention has been diverted to the role of costimulatory signaling pathway in organ transplantation. In this article, the latest research progress in costimulatory signaling pathway related to xenotransplantation immunity was reviewed, aiming to provide reference for the optimization of xenotransplantation immunosuppression regimen.

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.

Objective:To investigate the effect of total anatomical reconstruction (TAR) during robot-assisted radical prostatectomy (RARP) .Methods:The clinical data of 99 patients with RARP performed by a single doctor in our hospital from January 2018 to January 2021 were analyzed retrospectively.There were 38 patients in the TAR+ vesicourethral anastomosis (VUA) group and 61 patients in the VUA group. There were no significant differences between the two groups in the age of patients [ 65.5 (60.8, 71.0) years vs. 66.0 (61.5, 69.0) years], body mass index[ (24.92±2.65) kg/m 2 vs. (25.51±2.80) kg/m 2], prostate volume [28.13 (25.21, 36.53) ml vs. 26.33 (19.75, 47.84) ml], PSA [15.67 (9.02, 31.49) ng/ml vs. 14.58 (9.23, 30.06) ng/ml], neoadjuvant therapy [50.0% (19/38) vs. 63.9% (39/61)], Gleason score (6/7/8/9-10 scores: 8/16/5/9 cases vs. 16/25/9/11 cases) and clinical T stage (T 1/T 2/T 3 stage: 4/29/5 cases vs. 3/53/5 cases)(all P>0.05). The TAR technique was performed as follows. ①The two layers of posterior reconstruction involved the residual Denonvilliers fascia, the striated sphincter and medial dorsal raphe (MDR), and the vesicoprostatic muscle (VPM), the fascia which was 1-2 cm from the cranial side of the bladder neck and MDR. ②The one layer of anterior reconstruction involved detrusor apron, tissues around the urethra and the visceral and parietal layers of the endoplevic fascia. The VUA technique was suturing the bladder neck and urethra consecutively. Perioperative indexes were compared between the two groups. Results:All 99 operations were successfully completed. There were no statistically significant differences between the TAR+ VUA and VUA groups in operation time [ (174.16±47.21) min vs. (188.70±45.39) min], blood loss [ 50 (50, 100) ml vs. 100 (50, 100) ml], incidence of postoperative complications [10.5% (4/38) vs. 14.8% (9/61)], phathological T stage [pT 2/pT 3~4 stage: 25/12 cases vs. 42/19 cases, P=0.895], and the time of indwelling catheter [ 21.0 (19.0, 21.0) d vs. 21.0 (21.0, 21.0) d] (all P>0.05). The difference in postoperative length of stay between the two groups was statistically significant[6.0 (5.0, 6.0) d vs. 7.0 (6.0, 7.5)d, P<0.001]. Follow-up was performed for 1 year after surgery. The recovery rate of urinary continence 3 months after surgery in TAR+ VUA and VUA groups were 86.8% (33/38) vs. 65.6% (40/61), which were statistically significant( P=0.019). There were no significant differences between TAR+ VUA and VUA groups in recovery rate of urinary continence 1 months after surgery [47.4% (18/38) vs. 45.9% (28/61)], 6 months after surgery [94.7% (36/38) vs. 85.2% (52/61)], and 12 months after surgery [94.7% (36/38) vs. 93.4% (57/61)] (all P>0.05). Conclusions:TAR technique has good surgical safety, and can promote recovery of early urinary continence after RARP.

Objective:To investigate the relationship between the positive surgical margin and clinical factors such as neoadjuvant hormonal therapy after robot-assisted laparoscopic radical prostatectomy (RARP) in high-risk patients with prostate cancer.Methods:The clinical data of 164 patients with high-risk prostate cancer being performed RARP by one surgeon were analyzed retrospectively in our hospital from January 2016 to January 2022. The mean patient’s age was (65.3±6.2) years old, mean body mass index (BMI) was (25.6±3.0) kg/m 2, the median value of total prostate specific antigen (tPSA) before operation was 18.6(11.3, 31.3)ng/ml, the median value of Gleason score before operation was 7 (7, 8), the median value of prostate volume was 29.3 (22.4, 40.2) ml, and the clinical stage was T 2aN 0M 0-T 4N 0M 0. 80 patients with prostate cancer were treated with neoadjuvant endocrine therapy. All of them were treated with complete androgen blockade with a median course of 3 months. Univariate analysis was used to analyze the correlation between age, BMI, prostate volume, neoadjuvant hormonal therapy, preoperative tPSA, clinical stage, Gleason score before operation and positive surgical margin. Then multivariate logistic regression was used to further analyze the independent risk factor of positive surgical margin after RARP. Results:The postoperative pathological diagnosis included pT 2 stage in 111 cases (67.7%), pT 3a stage in 15 cases (9.1%), pT 3b stage in 25 cases (15.2%), pT 4 stage in 13 cases (7.9%). No lymph node metastasis was noticed in all patients. The Gleason scores included 6 in 11 cases (6.7%), 3+ 4 in 26 cases (15.9%), 4+ 3 in 36 cases (22.0%), 8 in 17 cases (10.4%), 9-10 in 24 cases (14.6%), un-evaluation due to endocrine therapy in 50 (30.5%). The positive surgical margin of high-risk patients with prostate cancer was 44.5% (73/164). Univariate analysis showed that the neoadjuvant hormonal therapy, tPSA and clinical stage were correlated with positive surgical margin ( P<0.05). Multivariate logistic regression analysis showed that non-neoadjuvant hormonal therapy, preoperative tPSA>20ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of high-risk patients with prostate cancer. Stratified analysis showed that when the preoperative tPSA was 10-20 ng/ml(21.1% vs.55.9%, P=0.014), the clinical stage was T 2c(29.6% vs.49.1%, P=0.040), the Gleason score before operation was 7(19.4% vs.54.1%, P=0.003), the positive surgical margin of high-risk patients in the neoadjuvant hormonal therapy group was significantly lower than that in the non-neoadjuvant hormonal therapy group ( P<0.05). Conclusions:Non-neoadjuvant hormonal therapy, preoperative tPSA>20 ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of RARP in the high-risk patients with prostate cancer. For high-risk patients with preoperative tPSA of 10-20 ng/ml, clinical stage of T 2c and Gleason score before operation of 7, neoadjuvant hormonal therapy has important clinical significance in reducing the positive surgical margin of RARP.