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

To evaluate the clinical efficacy of selective fetal reduction in the first trimester for the treatment of intrauterine pregnancy combined with cesarean scar pregnancy (CI-CSP), this article reports a 41-year-old pregnant woman diagnosed with CI-CSP after assisted reproductive technology. At 6 + weeks of gestation, mechanical fetal reduction surgery was performed under ultrasound guidance to eliminate the fetus at the scar site, and the fetal reduction was successful. The pregnancy lasted until 38 weeks of gestation. A healthy male infant was delivered by cesarean section. This case suggests that selective fetal reduction surgery can be a feasible option to preserve intrauterine pregnancy and reduce the risk of CI-CSP, but the indications and perioperative management need to be strictly controlled.

To evaluate the clinical efficacy of selective fetal reduction in the first trimester for the treatment of intrauterine pregnancy combined with cesarean scar pregnancy (CI-CSP), this article reports a 41-year-old pregnant woman diagnosed with CI-CSP after assisted reproductive technology. At 6 + weeks of gestation, mechanical fetal reduction surgery was performed under ultrasound guidance to eliminate the fetus at the scar site, and the fetal reduction was successful. The pregnancy lasted until 38 weeks of gestation. A healthy male infant was delivered by cesarean section. This case suggests that selective fetal reduction surgery can be a feasible option to preserve intrauterine pregnancy and reduce the risk of CI-CSP, but the indications and perioperative management need to be strictly controlled.

Abstract: Objective　The aim of this study was to observe the expression levels and clinical significance of peripheral blood interferon γ-inducible protein-10 (IP-10) and various cytokines in patients with different infection statuses of tuberculosis and to assess the efficacy of latent tuberculosis infection (LTBI) in the progression to active tuberculosis (ATB). Methods　Seventy-six outpatient and inpatient cases from the Third People's Hospital of Kunming were collected and analyzed from March 2023 to February 2024. The patients were divided into three groups: ATB group (31 cases, 17 males, median age 33 years), LTBI group (27 cases, 17 males, median age 29 years), and healthy control (HC) group (18 cases, 11 males, median age 25 years). Peripheral blood samples from the three groups were taken and the expression levels of IP-10 and cytokines IL-6, IL-4, IL-8, IL-10, IL-12, IL-2, and TNF-α were detected using enzyme-linked immunosorbent assay (ELISA) methods. The t-test was used for normally distributed samples, while the Mann-Whitney U test was used for skewed distributions. For comparisons between multiple groups, the Kruskal-Wallis H test was first employed, followed by Dunn's multiple comparison test for pairwise comparisons. Finally, the effectiveness of each cytokine in distinguishing different population groups was analyzed. Results　The expression levels of peripheral blood IP-10 were higher in the LTBI and ATB groups than in the HC group, but the area under the curve (AUC) of the receiver operating characteristic (ROC) of the subjects showed moderate sensitivity (AUC:0.7-0.9) and low specificity (AUC:0.5-0.7). The IL-6 expression levels were in the order of high to low in the ATB group, LTBI group, and HC group, where the HC group was significantly lower than the ATB and LTBI groups (F=12.15, P<0.001). The sensitivity and specificity of the ATB group were higher than those in the HC group. Conclusions　IP-10 exhibits unique advantages in distinguishing different tuberculosis statuses. The predictive efficacy of a single cytokine is limited. Combining multiple cytokines such as IL-6 with clinical manifestations, a more accurate and comprehensive prediction model can be established.

Objective To research the genetic susceptibility of proliferative diabetic retinopathy (PDR) in Han patients with type 2 diabetes from Southern China.Methods A cross-sectional study was performed under the informed consent of the patients.Patients with type 2 diabetes in the Dongguan Eye Study from September 2011 to February 2012 and relative patients treated in Guangdong General Hospital from July 2017 to March 2018 were included in this study,including 100 patients with diabetes mellitus(DM) and 120 patients with PDR.Whole exome sequencing was used to identify DNA mutation in peripheral blood samples from 22 type 2 diabetic patients without retinopathy (DM group) and 23 diabetic patients with PDR (PDR group).Genotype and allele of the nine selected single-nucleotide polymorphisms (SNPs) were tested and analyzed by SnaPshot technology in another 78 DM patients without retinopathy and 97 PDR patients.Results A total of 75 SNPs were associated with PDR (P＜0.01),involving 53 genes.Eleven gene loci were in the exon region and 7 were non-synonymous mutations.Nine exon loci of 8 genes with significant differences were screened out for the verification.SnaPshot SNP genotyping technique found that there were no significant differences in allele and genotype frequency in the nine selected SNPs between PDR group and DM group (all at P＞0.05).However,7 haplotypes distribution frequencies were significantly different between PDR group and DM group (all at P＜0.01).Hapl and Hap4 might reduce the risk of PDR (both at OR＜1,P＜0.05),and Hap2 might increase the risk of PDR (OR＞ 1,P＜0.05).Conclusions The occurrence of PDR probably has a genetic susceptibility in type 2 DM patients of Han nationality in Southern China.