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 construct a hypertension structured database based on Yi-9B large language model by aiming at the large amount of unstructured data generated in the process of hypertension diagnosis and treatment in order to elevate the efficiency of data management and provide the support for clinical deci-sion-making.Methods The key clinical informations of 114 369 patients with hypertension visiting in the Sec-ond Affiliated Hospital of Army Medical University during 2014-2023 were extracted.The Yi-9B large lan-guage model was used for conducting the entity identification and data structuring,and the database architec-ture was designed for statistical analysis and clinical application.Results After the database structuring process,the mean values of systolic and diastolic blood pressure were(149.98±20.55)mmHg and(86.90±13.75)mmHg,respectively.According to the classification of blood pressure level,the proportions of the nor-mal high value for high risk,very high risk of hypertension grade 1,and very high risk of hypertension grade 2 were the highest,which accounted for 20.73％,27.80％and 19.59％respectively.52.64％of the patients were complicated with heart disease,10.18％with complicating diabetes and 12.71％with complicating hy-perlipidemia.Logistic regression analysis showed that＞50-60 and＞60-70 years old was the high incidence age segment,moreover the systolic blood pressure showed an increasing trend with the age increase,reflecting the universality of hypertension in aging.This database significantly improved the efficiency of diagnosis and treatment in clinical application and realized the efficient analysis and management of data.Conclusion The hyper-tension structured database based on Yi-9B large language model effectively processes the unstructured data,significantly improves the efficiency of data extraction and management,helps to optimize the diagnosis and treatment decision-making,improves the management efficiency and provides the support for intelligent man-agement and personalized diagnosis and treatment.

Objective To construct the predictive model of pressure injury(PI)in the patients with chronic pain based on machine learning,and to analyze its accuracy and rationality,so as to provide an evidence for the predictive evaluation of clinical PI.Methods The clinical medical records data of 396 patients with chronic pain and high risk Braden scores hospitalized in a class 3A hospital of Chongqing City from March 2023 to June 2024 were retrospectively analyzed.Based on the Python3.10 programming language,the decision tree model,random forest model,linear regression model,naive Bayes model and K-Means model were con-structed,and the model performances were compared by accuracy,sensitivity,precision,F1 score and area un-der the receiver operating characteristic(ROC)curve(AUC).Results PI occurred in 35 cases with an inci-dence rate of 8.84%.Age,NRS score,pain site and pain affected sleep were the independent influencing fac-tors for the PI occurrence in the patients with chronic pain.Among 5 kinds of PI risk predictive model,the ac-curacy(0.873),sensitivity(0.874),precision(0.848),F1 score(0.844)and ROC AUC(0.81)of the ran-dom forest model were all higher than those of other models.Conclusion The random forest model has a high predictive performance for PI in the patients with chronic pain,and could be used for the screening and man-agement of high risk groups of PI in the patients with chronic pain.

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.

Objective:To preliminarily investigate the safety and efficacy of programmed death-1(PD-1)inhibitor combined with cord blood-derived natural killer cells(NK cells)in the treatment of advanced malignant solid tumors in an exploratory clinical trial.Methods:Three patients with advanced solid tumors treated at the Second Affiliated Hospital of Xi'an Medical University from December 2019 to December 2021 were enrolled.According to tumor type and CSCO guidelines,patients received multiple treatment cycles(21 days per cycle)consisting of standard chemotherapy,targeted therapy,or bevacizumab combined with PD-1 inhibitor.Umbilical cord blood-derived NK cells(8×107 cells per infusion)were infused at appropriate intervals during the treatment course.Target lesion size,tumor markers,levels of 12 peripheral blood cytokines,and lymphocyte subsets were assessed in each treatment cycle.Adverse events were also monitored throughout the treatment.Results:Following the treatment with PD-1 inhibitor combined with cord blood NK cells,2 patients achieved stable disease(SD,per RECIST 1.1 criteria),with durations of 118 days and 92 days,respectively.After NK cell infusion,patient#1 exhibited a marked decrease in the tumor marker CA199 to normal range and sustained for three follow-up periods;patient#2 showed significant reductions in tumor markers CA199,CA242,and CA724.Conclusion:The combination of NK cells with chemotherapy and PD-1 inhibitor demonstrates potential therapeutic efficacy for solid tumors.No severe immune-related adverse reactions were observed in the three patients enrolled in this study.

Long-term glucose metabolism disorders in patient with diabetes is often accompanied by dyslipidemia, especially the elevated level of low-density lipoprotein cholesterol (LDL-C). It is an important risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). Recent studies at home and abroad have also found that diabetes can lead to increased levels of proprotein convertase subtilisin/kexintype 9 (PCSK9). In view of the profound influence of PCSK9 overexpression on low density lipoprotein cholesterol level, cardiovascular risk and atherosclerosis, it is of great significance to explore whether hypoglycemic drugs can reduce the level of PCSK9 in the treatment of diabetes. We summarized the results of the study on the effects of various hypoglycemic drugs on circulating PCSK9 concentration in order to provide ideas for the optimal treatment of diabetes.

Long-term glucose metabolism disorders in patient with diabetes is often accompanied by dyslipidemia, especially the elevated level of low-density lipoprotein cholesterol (LDL-C). It is an important risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). Recent studies at home and abroad have also found that diabetes can lead to increased levels of proprotein convertase subtilisin/kexintype 9 (PCSK9). In view of the profound influence of PCSK9 overexpression on low density lipoprotein cholesterol level, cardiovascular risk and atherosclerosis, it is of great significance to explore whether hypoglycemic drugs can reduce the level of PCSK9 in the treatment of diabetes. We summarized the results of the study on the effects of various hypoglycemic drugs on circulating PCSK9 concentration in order to provide ideas for the optimal treatment of diabetes.

Objective To predict the tissue-level failure strain of the cortical bone and discuss the effects of different running speeds on the mechanical properties of rat femoral cortical bone.Methods The threshold for cortical bone tissue-level failure strain was assigned,and fracture simulation under three-point bending was performed on a rat femoral finite element model.The predicted load-displacement curves in each simulation were compared and fitted with the experimental data to back-calculate the tissue-level failure strain.Results The cortical bone tissue-level failure strains at different running speeds were statistically different,which indicated that different running speeds had certain impacts on the micromechanical properties of the cortical bone structures.At a running speed of 12 m/min,the cortical bone structure expressed the greatest tissue-level failure strain,and at a running speed of 20 m/min,the cortical bone structure expressed the lowest tissue-level failure strain.Conclusions Based on the changing trends of tissue-level failure strain and in combination with the changes in macro-level failure load and tissue-level elastic modulus of cortical bone structures,the effects of different running speeds on the mechanical properties of cortical bone structures were discussed in this study.The appropriate running speed for improving the mechanical properties of the cortical bone was explored,thereby providing a theoretical basis for improving bone strength through running exercises.

Objective:To investigate the efficacy of different treatment modes for locoregional recurrence after nephrectomy in patients with renal cell carcinoma.Methods:A total of 106 patients with locoregional recurrence after nephrectomy without distant metastasis (77 males and 29 females) admitted to Sun Yat-sen University Cancer Center from October 2001 to July 2020 were retrospectively analyzed. The median age was 51 (40, 60) years old. Radical nephrectomy was performed in 90 patients with primary tumor and partial nephrectomy was performed in 16 patients. Pathological diagnosis showed that 54 cases were clear cell carcinoma and 52 cases were non-clear cell carcinoma. 53 cases were in stage T 1-2 and 53 cases in stage T 3-4. The median diameter of recurrent lesions was 3.2 (2.0, 6.3) cm, and the median number was 2 (1, 4). The recurrence sites were divided into renal fossa recurrence (33 cases), renal fossa±retroperitoneal lymph node recurrence (38 cases), and intra-abdominal spread (35 cases). The median duration from primary surgery to local recurrence was 14.8 (7.3, 35.8) months. Two treatment groups were identified as systemic therapy alone (Group A) and local therapy with or without systemic therapy (Group B). The Kaplan-Meier method was used to compare the progression free survival (PFS) and overall survival (OS) between Group A and Group B. The Cox model was used to perform univariate and multivariate analysis. Results:Of all the 106 patients, 33 patients were in Group A and 73 patients were in Group B. In Group A, 29 patients (87.9%) received targeted therapy, and 4 patients (12.1%) received targeted therapy combined with immunotherapy. In Group B, 34 patients (46.6%) received surgery or ablation and 39 patients (53.4%) received SBRT, of which 62 patients (84.9%) received concurrent systemic therapy. Among them, 58 patients (93.5%) received targeted therapy, and 4 patients (6.5%) received targeted therapy combined with immunotherapy. The median follow-up period was 29.0 (15.4, 45.9) months, 64 patients progressed on tumor including 28 patients died. The median PFS and OS were 15.6 (7.1, 35.2) months and 66.9 (37.8, not reached) months. The median PFS of Group A and Group B were 7.6(5.0, 17.2)months and 22.2(9.6, 63.9)months respectively ( P=0.001), median OS of Group A and Group B were 45.7 (23.4, 62.8)months and 71.0(50.6, not reached)months respectively, and the 2-year OS were 70.6% and 85.5% in Group A and Group B respectively ( P=0.023). The univariate analysis showed local therapy with or without systemic therapy was significantly reduced 56% risk of tumor progression ( HR=0.44, P=0.003) and reduced 60% risk of death ( HR=0.40, P=0.028). The multivariate analysis showed that the OS was associated with ECOG score( HR=10.20, 95% CI 4.13-25.30, P<0.001)and local therapy( HR=0.23, 95% CI 0.09-0.58, P=0.002). Conclusion:Compared with systemic therapy alone, local therapy with or without systemic therapy can effectively improve the PFS and OS of patients with locoregional recurrence after nephrectomy.

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.