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 discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.

Objective:To systematically evaluate the efficacy and safety of laparoscopic transcystic approach with micro-incision of the cystic duct confluence in common bile duct exploration (LTM-CBDE) versus laparoscopic common bile duct exploration (LCBDE) for the treatment of choledocholithiasis.Methods:PubMed, Library, Embase, Cochrane, CNKI, VIP, CBMdisc, Wanfang and other databases were searched to collect relevant literature about LTM-CBDE treatment of choledocholithiasis from December 2013 to December 2023. The main observational indexes were operation time, intraoperative bleeding, drainage tube banding time, postoperative gastrointestinal function recovery time, hospitalization time and postoperative complication rate. Meta-analysis was performed using Review Manager 5.4 software.Results:A total of 15 studies were collected, including one in English and 14 in Chinese. Five were randomized controlled clinical trials and 10 were case-control studies. A total of 1 493 patients, including 690 males and 803 females, aged (53.7±9.2) years old. Among them, 732 patients underwent LTM-CBDE as the microdissection group and 761 patients underwent LCBDE as the control group. Compared with the control group, the meta-analysis showed that patients in the microdissection group had a shorter drain banding time ( MD=-3.34, 95% CI: -4.69--1.99, P<0.001), a faster recovery time of postoperative gastrointestinal function ( MD=-0.63, 95% CI: -1.00--0.25, P=0.001), a shorter hospital stay ( MD=-2.18, and 95% CI: -2.79--1.57, P<0.001), and a lower incidence of bile leak ( OR=0.36, 95% CI: 0.22-0.59, P<0.001) and overall complications ( OR=0.28, 95% CI: 0.18-0.42, P<0.001). Conclusion:LTM-CBDE is safer and more effective than LCBDE in the treatment of choledocholithiasis and deserves clinical promotion.

Objective To explore the expression and significance of peripheral blood T lymphocyte subgroups and natural killer cell in children with asthmatic pneumonia.Methods From 2013 to 2016,asthmatic children with pneumonia were erolled in the study as asthmatic pneumonia group(36 cases) and 36 cases medical health children as control group at the same time in Zhongshan City people′s hospital.Flow cytometry was used to test analysis of two groups of T lymphocyte subsets and natural killer cell in serum and the expression of CD28,CD56,using ROC curve analysis results.Results Asthmatic pneumonia group compared with control group,the difference of CD3+ and CD3+CD8+,CD28+,CD8+CD28+,CD8+CD28-,CD3-CD16+CD56+ and CD3+CD16+CD56+,CD3+CD4+/CD3+ CD8+ was statistically significant(P<0.05).According to the results of flow parameters have higher sensitivity by the ROC curve statistics.Conclusion Asthmatic pneumonia children have immune dysfunction,immune function changes associate with asthmatic,which is of great clinical significance to carry out immune function detection for children with asthmatic pneumonia.

Objective To investigate the changes and clinical significance of CD19 ,CD20 ,CD3-CD16+ CD56+ (NK cells) and CD3+CD16+CD56+ (NKT cells) in the children with epilepsy .Methods 125 cases of children with epilepsy children confirmed by Pediatric neurology specialists in Zhongshan People's Hospital from January 2013 to March 2016 were selected as epilepsy group , while 125 cases of healthy children were selected as control group ,and the levels of CD19 ,CD20 ,NK cells and NKT cells in periph-eral blood of two groups were detected by flow cytometry .Results CD19 ,CD20 ,NK cells and NKT cells levels in epilepsy group were higher than those in control group ,and the difference was statistically significant (P<0 .05) .For ROC curve analysis ,CD19 optimal cutoff value of 9 .4 ,the area under the curve was 90 .3% ,with 91 .7% sensitivity .CD20 optimal cutoff value of 7 .75 ,the ar-ea under the curve was 87 .3% ,with 91 .7% sensitivity .NK cells optimal cutoff value of 8 .55 ,the area under the curve was 80 .5% , with 95 .8% sensitivity .NKT cells optimal cutoff value of 0 .35 ,the area under the curve was 76 .9% ,with 91 .7% sensitivity .Con-clusion CD19 ,CD20 ,NK cells and NKT cells can be used as important indexes for monitoring immune conditions in children with epilepsy .