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.

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.

L-homophenylalanine (L-HPA) is an important non-natural amino acid that has been used as a key intermediate for the synthesis of Puli drugs for the treatment of hypertension. At present, L-HPA is synthesized using chemical methods, which has the disadvantages of expensive raw materials, tedious steps and serious pollution. Therefore, researchers have conducted in-depth research on the enzymatic production of L-HPA. This review summarizes the research progress on the enzymatic synthesis of L-HPA, including the dehydrogenase process, the transaminase process, the hydantoinase process, and the decarboxylase process, with the hope to facilitate the industrial production of L-HPA.
Amino Acids ; Environmental Pollution ; Industry ; Protein Biosynthesis

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.

Platycodon grandiflorus polysaccharide (PGP) is one of the main components of P. grandiflorus, but the mechanism of its anti-inflammatory effect has not been fully elucidated. The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and explore the underlying mechanisms. The results showed that PGP treatment inhibited the weight loss of DSS-induced UC mice, increased colon length, and reduced DAI, spleen index, and pathological damage within the colon. PGP also reduced the levels of pro-inflammatory cytokines and inhibited the enhancement of oxidative stress and MPO activity. Meanwhile, PGP restored the levels of Th1, Th2, Th17, and Treg cell-related cytokines and transcription factors in the colon to regulate colonic immunity. Further studies revealed that PGP regulated the balance of colonic immune cells through mesenteric lymphatic circulation. Taken together, PGP exerts anti-inflammatory and anti-oxidant effect and regulates colonic immunity to attenuate DSS-induced UC through mesenteric lymphatic circulation.
Animals ; Mice ; Colitis, Ulcerative/drug therapy* ; Platycodon ; Colon/pathology* ; Cytokines ; Anti-Inflammatory Agents/therapeutic use* ; Polysaccharides/therapeutic use* ; Dextran Sulfate ; Disease Models, Animal ; Colitis/chemically induced* ; Mice, Inbred C57BL

Objective:To investigate the effects of types of ulnar styloid process fracture on the treatment of distal radius fracture.Methods:The 80 patients were analyzed retrospectively who had been treated at The First Department of Hand Surgery, Honghui Hospital from January 2019 to January 2020 for fracture of distal radius complicated with fracture of ulnar styloid process. They were 25 males and 55 females, aged from 30 to 85 years (average, 58.6 years). According to the types of ulnar styloid process fracture, 40 patients were assigned into a Hauck type Ⅰ group and the other 40 into a Hauck type Ⅱ group. The 2 groups were compared in terms of operation, postoperative complications, hospital stay, bone union, visual analogue scale (VAS) on postoperative 1 to 3 days, and modified Mayo wrist function score, wrist range of motion and quality of life by WHOQOL-BREF at the last follow-up.Results:The 2 groups were comparable because there was no significant difference in age, gender, American Society of Anesthesiologists (ASA) rating, or time from injury to operation between them ( P>0.05). All the patients were followed up for 12 to 24 months (average, 17 months). There was no significant difference between Hauck type Ⅰ group and Hauck type Ⅱ group in operation time, intraoperative blood loss, hospital stay, rate of postoperative complications, fracture union, modified Mayo wrist function score or VAS on postoperative 1 to 3 days ( P>0.05). At the last follow-up, the palm tilt and ulnar inclination angles were 13.8°±1.9° and 21.6°±2.8° in Hauck type Ⅰ group, significantly larger than those in Hauck type Ⅱ group (11.9°±1.6° and 18.8°±2.3°) ( P<0.05). At the last follow-up, Hauck Ⅰ group scored 85.3±6.4,85.6±6.5, 84.7±6.3 and 85.0±6.7 respectively in the domains of physical health, psychology, environment and social relationships, significantly higher than those Hauck type Ⅱ group did (78.5±6.5, 78.9±6.5, 77.8±6.1 and 77.9±6.3) ( P<0.05). Conclusions:In open reduction and internal fixation for distal radius fracture, Hauck Type Ⅰ fracture of ulnar styloid process has no significant effect on the functional recovery of the wrist but Hauck Type Ⅱ fracture of ulnar styloid process may. Therefore, surgical fixation needs to be strengthened if Hauck Type Ⅱ fracture of ulnar styloid process is complicated.

Objective To investigate the clinical effect of infective foot ulcer and soft tissue defects of small area with free peroneal artery perforator flap.Methods From February,2016 to Apirl,2017,9 cases of infective foot ulcer and soft tissue defect of small area were repaired with peroneal artery perforator flap.Cause of infection:injury in 6 cases,diabetes in 2 cases,spinal cord injury subsequent pressure sore in 1 case.Infective ulcer part:4 cases on plantar metatarsophalangeal joint,2 cases on dorsal metatarsophalangeal joint,2 cases on interior of the first metatarsophalangeal joint and 1 case on the heel.Defect area:3.0 cm×2.0 cm-5.0 cm×3.0 cm;flap area:4.0 cm×3.5 cm-7.0 cm×4.5 cm.The donor sites were sutured directly.All the flaps contained lateral sural cutaneous nerve.In order to rebuild the sensation of flaps,nerves between surgical area and receiving area were received end-to-side anastomosis.Outpatient follow-up was used in all patients.Results All the flaps survived,and all the wounds were primary healed,without recurrence of infection.All patients were followed-up from 6 to 24 months with an average of 16 months.The appearance of flaps was good with slight bloated.The texture and color of the flaps were close to the recipient site.Flap feel was good except the cases of diabetes and spinal cord injury pressure sore.The AOFAS score at last follow-up time was 80.05±7.80,which was excellent in 5 cases,good in 2 cases,and fair in 2 cases.Conclusion The free peronerl artery perforator flap has many advantages,such as vascular anatomy constant,blood supply is reliable,thickness moderate,easy to get,strong resistance to infection,small district damage,etc.It is a useful clinical method to repair foot infection ulcer and soft issue defects of small area.

Objective To explore the clinical application and effect of fibular head compound soft tissue flap transplantation on precision repairing of compound tissue defect at limb joints assisted by 3-Dimensional contrast printing technology.Methods From March,2014 to September,2017,9 patients with bone and soft tissue defect at limb joints were selected.In which,2 were distal radius bone defect with joint capsule and ligament defect,2 were lower segment tibia bone and soft tissue defect,2 were femur under section of the bone and soft tissue defect,2 were medial malleolus bone and ligament defect,and 1 was external ankle ligament and bone defect.Using 3-Dimensional printing to conduct bilateral mirror-image contrast prior to the operation,morphology of bone defect at limb joints was acquired.Based on the texture printed out,corresponding fibular head compound blocks with blood vessels were removed from the donor site and transplanted to the recipient site before anastomosing the blood vessels and restoring the blood flow.The regular post-operative followed-up was performed.Results The 9 transplanted tissue blocks survived.The donor sites and the recipient sites were healed.The followed-up for restoration of limb function was from 9 to 35 (average,17.5) months.The ankle function was assessed according Kofoed scale,resulted in 2 excellent and 1 good;The wrist function was assessed according Mayo scale,resulted in 1 excellent and 1 good.The medial malleolus bone defect and criteria bone defect were healed at 6 months.The patients were satisfied with the efficacy.Conclusion The application of 3-Dimensional contrast printing of fibular head compound tissue flap transplantation in repairing compound tissue defects at limb joints can reduce damage to the donor site,realizing precise repairing on limb tissue defect,and make good function restoration.