BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Objective To investigate the impact of two different surgical methods, orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, on the surgical outcomes of pig-to-pig kidney transplantation and the short-term survival of recipient pigs after surgery. Methods Twenty-four Bama miniature pigs were divided into two groups, with 12 pigs in each group, and underwent orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, respectively. The perioperative indicators of the recipient pigs, renal blood perfusion, the overall incidence rate of complications and survival rate were compared between the two surgical methods. Results The total surgical time, renal artery anastomosis time, renal vein anastomosis time, cold ischemia time and total ischemia time were all shorter in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group, with statistically significant differences (all P<0.05). The number of satisfactory renal perfusion cases was higher in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group (83% vs. 75%), but the difference was not statistically significant (P>0.05). The total incidence of postoperative complications was 33% in the heterotopic kidney transplantation group, with a survival rate of 92%, and the cause of death was rupture of the vascular anastomosis. The total incidence of postoperative complications was 50% in the orthotopic kidney transplantation group, with a survival rate of 83%, and the causes of death were renal vein thrombosis and renal artery thrombosis. There were no statistically significant differences in the total incidence of postoperative complications and survival rates between the two groups (all P>0.05). Conclusions Compared with orthotopic kidney transplantation, abdominal heterotopic kidney transplantation showes better surgical outcomes in pig-to-pig kidney transplantation and is more beneficial for the short-term survival of recipient pigs after surgery. This provides experience for improving the stability of pig-to-non-human primate kidney xenotransplantation models in the future.

Pain not only affects the physical and mental health of individuals, but also imposes a huge burden on society as a whole. Traditional pain management measures are diverse, but each has its limitations. Therefore, there is an urgent need for new tools. Digital therapies are booming, and virtual reality (VR) has been widely used, especially in the field of pain management. VR uses assistive tools, such as headsets, to build a three-dimensional virtual world with the participation of multiple senses, including vision, hearing, and smell, so that it can make user feel being there. This review aims to summarize the application and mechanism of VR in the field of pain management, with the hope of making VR a new choice for pain management.

Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.

【Objective】 To explore the factors influencing erectile dysfunction (ED) in male patients after renal transplantation, so as to provide basis for the prevention and treatment of this disease. 【Methods】 Kidney transplant recipients followed up in the Kidney Transplant Clinic of Xijing Hospital during Sep.1, 2022 and May 1, 2023 were selected as the study objects.Questionnaires were distributed, and the erectile function was measured with Sexual Health Inventory for Men (SHIM).Factors associated with ED were analyzed with multivariate logistic regression. 【Results】 A total of 300 questionnaires were distributed, and 276 valid ones were collected, including 182 cases (65.9%) suffering from ED of varying degrees.Multivariate logistic regression analysis showed that age [(<30 years/>50 years, OR: 0.120, 95%CI: 0.033-0.405, P<0.001), (30-40 years/>50 years, OR: 0.223, 95%CI: 0.102-0.463, P<0.001), (>40-50 years/>50 years, OR: 0.320, 95%CI: 0.139-0.719, P<0.01)], level of International Prostate Symptom Score (IPSS) (OR: 1.95, 95%CI: 1.211-3.248, P<0.01), International Prostate Symptom Score-Quality of Life item (IPSS-QoL) (OR: 1.482, 95%CI: 1.201-1.854, P<0.01), and income [(≥10 000 Yuan/<3 000 Yuan, OR: 0.156, 95%CI: 0.053-0.429, P<0.001), (5 000-<10 000 Yuan/<3 000 Yuan, OR: 0.418, 95%CI: 0.199-0.864, P<0.05), (≥10 000 Yuan/3 000-<5 000 Yuan, OR: 0.205, 95%CI: 0.069-0.573, P<0.01)] were independent and significant factors of ED. 【Conclusion】 The prevalence of ED in renal transplantation recipients is high.Age, income, IPSS and IPSS-QoL are the influencing factors.ED after renal transplantation is not only determined by physical and functional factors, but also closely related to social and psychological factors.

【Objective】 To analyze the correlation between the expressions of CD10,CA9 and CD133 and the prognosis of patients with metastatic renal clear cell carcinoma (mccRCC) treated with sorafenib or sunitinib. 【Methods】 A total of 80 mccRCC patients who received sorafenib or sunitinib as first-line therapy were retrospectively enrolled. Immunohistochemical staining (IHC) was performed for CD10,CA9 and CD133 in tumor tissue samples to analyze the correlation between the expression of each marker and clinicopathologic variables. Univariate and multivariate Cox proportional risk models were used to analyze prognostic factors of progression free survival (PFS) and overall survival (OS),and Kaplan-Meier survival analysis was performed for CA9 expression and PFS,OS in the treatment subgroups. 【Results】 Altogether 37 patients (46.25%) had PFS,and the median PFS (mPFS) was 24.9 months (95%CI:16.5-33.2 months),while 55 patients (68.75%) died and the median OS (mOS) was 44.2 months (95%CI:14.6-73.7). Low expression of CD10 was correlated with high Fuhrman grade (χ²=6.241,P=0.012),lymph node metastasis (χ²=5.952,P=0.015),and the number of metastatic organs ≥2 (χ²=8.205,P=0.004). Univariate analysis showed that Fuhrman grade,number of metastatic organs and lymph node metastasis were the prognostic factors of PFS (P<0.05),while the number of metastatic organs,lymph node metastasis and CA9 expression were the prognostic factors of OS (P<0.05). Multivariate analysis showed that Fuhrman grade was an independent factor of PFS (HR=2.457,95%CI:1.126-5.365,P=0.024),and the number of metastatic organs was an independent prognostic factor of OS (HR=1.857,95%CI:1.048-3.290,P=0.034). Survival analysis in subgroups showed that high CA9 expression in the sorafenib group was associated with longer OS (HR=0.401,95%CI:0.204-0.787,P=0.008). 【Conclusion】 Low expression of CA9 is an non-independent risk factor for OS,while CD10 and CD133 cannot be used as prognostic factors for mccRCC patients. Since mccRCC patients with low CA9 expression have less survival benefit from sorafenib and sunitinib,they can choose target therapy combined with immunotherapy or dual immunotherapy according to the guidelines to improve prognosis.

Objective To evaluate the clinical efficacy of adult kidney transplantation from unilateral pediatric donor kidney. Methods Clinical data of pediatric donors (n=10) and adult recipients (n=19) undergoing kidney transplantation were retrospectively analyzed. The changes of renal function, liver function and the maximal diameters of the kidney allografts were compared at 1, 7, 14, 28, 60 d after operation. The short-term survival and incidence of postoperative complications of the recipients were analyzed. Results Ten donors included 6 males and 4 females, aged (7±3) years old, with a body mass index (BMI) of (16.3±3.8) kg/m². All donors were donation after brain death followed by cardiac death. Among 19 recipients, 12 were males and 7 were females, aged (34±12) years old, with a BMI of (20.3±1.3) kg/m².An oblique incision was created in the lower right abdomen of the recipients. The arteries and veins of donor kidney were anastomosed with the external iliac arteries and veins of the recipients. The ureter of donor kidney was anastomosed with the bladder of the recipients. After anastomosis, the kidney was placed and fixed in the right iliac fossa. The serum creatinine and blood urea nitrogen levels of the recipients were decreased at 1 week after kidney transplantation, and restored to normal range at postoperative 2 weeks. All parameters related to liver function were normal after operation. At postoperative 1 month, the maximal diameters of the kidney allografts were (9.5±0.3) cm on average, which basically reached those of normal adults. The 1-year survival rate of 19 recipients was 95%. One recipient died from pulmonary infection after ineffective treatment. Two recipients developed rejection, and 1 recipient experienced urinary system infection, who were healed after corresponding treatment. Conclusions Adult kidney transplantation from unilateral pediatric donor kidney is safe, feasible and effective, which can be utilized to enlarge the source of donor kidneys.

Objective To compare the early clinical efficacy of renal transplantation between extended criteria donor (ECD) and standard criteria donor (SCD). Methods Clinical data of 85 recipients undergoing renal transplantation from donation after cardiac death (DCD) were retrospectively analyzed. According to the types of donors, all recipients were divided into the ECD group (n=31) and SCD group (n=54). The level of serum creatinine (Scr), incidence of early complications and clinical prognosis within 3 months after renal transplantation were compared between 2 groups. Results No statistical significance was observed in the levels of Scr within 1 month after renal transplantation between the ECD group and SCD group (all P>0.05). At postoperative 60 and 90 d, the level of Scr in the ECD group was (189±97) and (175± 69) μmol/L respectively, significantly higher than (142±49) and (135±41) μmol/L in the SCD group (P=0.005 and 0.002). In the ECD group and SCD group, the incidence of acute rejection (AR) was 6% and 15%, the incidence of delayed graft function (DGF) was 23% and 19%, the incidence of pulmonary infection was 10% and 6%, the incidence of other early complications was 32% and 15%, respectively, no statistical significance was identified (all P>0.05). In the ECD group and SCD group, the survival rate of the recipient was 97% and 94%, the survival rate of the renal was 84% and 91%, no statistical significance was identified (all P>0.05). Conclusions Compared with the SCD, renal transplantation from ECD can achieve equivalent early clinical efficacy. In the present condition of serious deficiency of donor kidney, the application of ECD can enlarge the supply of the donor kidney.

Objective To explore the skills and summarize the experience in the establishment of orthotopic liver transplantation rat models from donation after cardiac death (DCD). Methods According to the time of warm ischemia, 120 rats were divided into 3 groups: group A (warm ischemia for 0 min, n=40 pairs), group B (warm ischemia for 10 min, n=40 pairs) and group C (warm ischemia for 20 min, n=40 pairs). Orthotopic liver transplantation was performed by the modified two-cuff technique in 3 groups. The time of each stage of surgery was recorded in 3 groups. The survival rate at the end of surgery, 24 h, 72 h and 7 d after surgery was recorded in 3 groups. The dead rats were immediately subject to anatomical examination to identify the cause of death. Results The cold ischemia time of donor liver, anhepatic phase and operation time of the recipients did not significantly differ among three groups (all P>0.05). In groups A, B and C, the survival rate at the end of surgery was 97%, 97%, and 100% respectively. The survival rate at postoperative 24 h was 92%, 90% and 92% respectively. The survival rate at postoperative 72 h was 90%, 80% and 77% respectively. The survival rate at postoperative 7 d was 85%, 70% and 57% respectively. The survival rate at the end of surgery, postoperative 24 h and 72 h did not significantly differ among 3 groups (all P>0.05). At postoperative 7 d, the survival rate in group C was significantly lower than that in group A (P<0.05). Surgical operation was the major cause of intraoperative and postoperative 24 h death. Bile leakage and ischemic hepatic failure were the causes of death at postoperative 72 h. Biliary duct complications were the main causes of death at postoperative 7 d. The quantity of rats developing with biliary duct complications was increased along with the prolongation of warm ischemic time. Conclusions The success of stable establishment of rat models with orthotopic liver transplantation from DCD depends upon the protection of the liver and biliary function. The difficulty lies in the anastomosis of the suprahepatic inferior vena cava and the shortening of anhepatic phase.

Objective To analyze the follow-up results and clinical characteristics of one case of highly sensitized recipient after combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation.Methods This patient was diagnosed as having chronic renal insufficiency in the uremia period 10 years ago,subjected to kidney transplantation 9 years ago,and got renal allograft loss 8 years ago.The recipient was positive for PRA (for class Ⅰ,31％,and for class Ⅱ,63％).Under the general anesthesia,the patient was given combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation.The ATG was used for immune induction.Rituximab and plasma exchange were applied to prevent acute rejection.Regular follow-up was done after discharge.Results On the postoperative day (POD) one,ALT was 256 IU/L,AST was 342 IU/L and serum creatinine was 502 μmol/L.On the POD 6,ALT and AST levels were normal and serum creatinine was 141 μmol/L.Serum creatinine increased to 202 μmol/L and the volume of urine reduced on the POD 7.The ultrasound displayed graft size increased slightly,substantial echogenicity enhanced,artery blood flow RI increased to 0.8,suggesting the occurrence of acute rejection.A single dose of Rituximab,intravenous IG,and plasma exchange were given.On the POD 60,serum creatinine was reduced to 131 μmol/L.During a follow-up period of 28 months,imrnunosuppresants were given:Tac + MMF + Pred.FK506 valley concentration was maintained at 6-8 μg/L.The function of the transplanted kidney and liver was normal,and the general conditions were good.Conclusion Combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation is safe.Individualized medication and regular follow-up are the important factors for long-term survival of recipients.