Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

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.

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 association of serum apolipoprotein A1 (Apo-A1) and tumor abnormal protein (TAP) with recurrence risk after transurethral resection of bladder tumor (TURBT) in patients with bladder cancer.Methods:The data of 120 patients with bladder cancer who received TURBT treatment and were followed up in Xi′an Daxing Hospital from April 2018 to April 2021 were retrospectively collected. According to the recurrence data after 3 years of follow-up, the patients were divided into recurrence group (29 cases) and non-recurrence group (91 cases). Baseline data, serum Apo-A1, TAP levels and other laboratory indicators at the last preoperative examination were collected and compared between the two groups. Cox regression analysis was performed to determine the association of serum Apo-A1, TAP with recurrence in these patients after TURBT. The dose-response relationship between serum Apo-A1, TAP and risk of recurrence after TURBT in patients with bladder cancer was analyzed by restricted cubic spline method. The interaction of serum Apo-A1 and TAP on recurrence after TURBT in patients with bladder cancer was analyzed.Results:During the follow-up period of 3 years, the disease recurred in 29 patients, with recurrence time from 16 to 33 months, and with the median recurrence time of 25.00 (20.50, 29.50) months. The proportion of tumor TNM stageⅡ, tumor pathological grade G 2, non intravesical bacillus Calmette-Guérin perfusion after operation and serum Apo-A1, TAP, nuclear matrix protein 22, bladder tumor antigen levels in the recurrence group were higher than those in the non-occurrence group: 72.41% (21/29) vs. 50.55% (46/91), 34.48% (10/29) vs. 14.29% (13/91), 31.03% (9/29) vs. 12.09% (11/91), (29.45 ± 4.78) μg/L vs. (24.81 ± 4.25) μg/L, (165.37 ± 10.28) μm 2 vs. (156.33 ± 9.92) μm 2, (31.11 ± 5.21) μg/L vs. (28.29 ± 5.13) μg/L, (27.93 ± 4.18) μg/L vs. (25.57 ± 4.95) μg/L, and the differences were statistically significant ( P<0.05). Cox regression analysis showed that the recurrence after TURBT was related to the levels of serum Apo-A1, TAP and nuclear matrix protein 22 ( P<0.05). The results of restricted cubic spline analysis showed that there was a linear dose-response relationship between serum Apo-A1, TAP levels and the risk of recurrence after TURBT in patients with bladder cancer ( P<0.05). When serum Apo-A1≥25.50 μg/L and TAP≥159.20 μm 2, the risk of postoperative recurrence increased with the increase of their expression. There was a positive interaction between serum Apo-A1 and TAP on the recurrence after TURBT in patients with bladder cancer. The risk of recurrence in patients with high expression of both was 25.25 times that of patients with low expression of both, and the synergistic effect was 1.521 times that of the sum of the effects of the two alone. In the risk of tumor recurrence, 32.95% was caused by the interaction between the two. Conclusions:The risk of recurrence after TURBT in patients with bladder cancer may be related to the levels of serum Apo-A1 and TAP. Increase of the two levels may be a risk factor for postoperative recurrence, and there is a significant dose-response relationship between the two, and there is a positive interaction with tumor recurrence.

[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

Objective To investigate the clinical features,treatment and prognosis of primary testicular lymphoma(PTL),so as to provide reference for the standardized diagnosis and treatment of this disease.Methods Clinical data of 13 PTL cases treated in Xijing Hospital during Jan.2014 and Dec.2024 were retrospectively collected.The patients' diagnosis,treatment methods and prognosis were summarized.Results All 13 patients underwent orchiectomy of the affected side.According to the postoperative pathological results,11 cases were diagnosed as diffuse large B-cell lymphoma and 2 as NK/T-cell lymphoma.Among the 11 cases with diffuse large B-cell lymphoma,10 received immunotherapy and chemotherapy according to the international standardized treatment plan,and 5 received preventive myeloablative injection therapy.Recurrence in the contralateral testis occurred in 3 cases,1 complicated with central nervous system infiltration died,and another 1 refusing chemotherapy had contralateral testicular metastasis.Of the 2 cases with NK/T-cell lymphoma,1 received systemic chemotherapy and died after central nervous system recurrence,and another 1 died 1 month after surgery whithout undergoing chemotherapy.Conclusion Primary testicular lymphoma is highly invasive with poor prognosis.Patients with NK/T-cell lymphoma have extremely poor prognosis,while those with diffuse large B-cell lymphoma have relatively better prognosis.However,even after comprehensive treatment,it is still prone to recurrence in the testis and the central nervous system.

Objective To investigate the clinical features,treatment and prognosis of primary testicular lymphoma(PTL),so as to provide reference for the standardized diagnosis and treatment of this disease.Methods Clinical data of 13 PTL cases treated in Xijing Hospital during Jan.2014 and Dec.2024 were retrospectively collected.The patients' diagnosis,treatment methods and prognosis were summarized.Results All 13 patients underwent orchiectomy of the affected side.According to the postoperative pathological results,11 cases were diagnosed as diffuse large B-cell lymphoma and 2 as NK/T-cell lymphoma.Among the 11 cases with diffuse large B-cell lymphoma,10 received immunotherapy and chemotherapy according to the international standardized treatment plan,and 5 received preventive myeloablative injection therapy.Recurrence in the contralateral testis occurred in 3 cases,1 complicated with central nervous system infiltration died,and another 1 refusing chemotherapy had contralateral testicular metastasis.Of the 2 cases with NK/T-cell lymphoma,1 received systemic chemotherapy and died after central nervous system recurrence,and another 1 died 1 month after surgery whithout undergoing chemotherapy.Conclusion Primary testicular lymphoma is highly invasive with poor prognosis.Patients with NK/T-cell lymphoma have extremely poor prognosis,while those with diffuse large B-cell lymphoma have relatively better prognosis.However,even after comprehensive treatment,it is still prone to recurrence in the testis and the central nervous system.

Objective:To investigate the association of serum apolipoprotein A1 (Apo-A1) and tumor abnormal protein (TAP) with recurrence risk after transurethral resection of bladder tumor (TURBT) in patients with bladder cancer.Methods:The data of 120 patients with bladder cancer who received TURBT treatment and were followed up in Xi′an Daxing Hospital from April 2018 to April 2021 were retrospectively collected. According to the recurrence data after 3 years of follow-up, the patients were divided into recurrence group (29 cases) and non-recurrence group (91 cases). Baseline data, serum Apo-A1, TAP levels and other laboratory indicators at the last preoperative examination were collected and compared between the two groups. Cox regression analysis was performed to determine the association of serum Apo-A1, TAP with recurrence in these patients after TURBT. The dose-response relationship between serum Apo-A1, TAP and risk of recurrence after TURBT in patients with bladder cancer was analyzed by restricted cubic spline method. The interaction of serum Apo-A1 and TAP on recurrence after TURBT in patients with bladder cancer was analyzed.Results:During the follow-up period of 3 years, the disease recurred in 29 patients, with recurrence time from 16 to 33 months, and with the median recurrence time of 25.00 (20.50, 29.50) months. The proportion of tumor TNM stageⅡ, tumor pathological grade G 2, non intravesical bacillus Calmette-Guérin perfusion after operation and serum Apo-A1, TAP, nuclear matrix protein 22, bladder tumor antigen levels in the recurrence group were higher than those in the non-occurrence group: 72.41% (21/29) vs. 50.55% (46/91), 34.48% (10/29) vs. 14.29% (13/91), 31.03% (9/29) vs. 12.09% (11/91), (29.45 ± 4.78) μg/L vs. (24.81 ± 4.25) μg/L, (165.37 ± 10.28) μm 2 vs. (156.33 ± 9.92) μm 2, (31.11 ± 5.21) μg/L vs. (28.29 ± 5.13) μg/L, (27.93 ± 4.18) μg/L vs. (25.57 ± 4.95) μg/L, and the differences were statistically significant ( P<0.05). Cox regression analysis showed that the recurrence after TURBT was related to the levels of serum Apo-A1, TAP and nuclear matrix protein 22 ( P<0.05). The results of restricted cubic spline analysis showed that there was a linear dose-response relationship between serum Apo-A1, TAP levels and the risk of recurrence after TURBT in patients with bladder cancer ( P<0.05). When serum Apo-A1≥25.50 μg/L and TAP≥159.20 μm 2, the risk of postoperative recurrence increased with the increase of their expression. There was a positive interaction between serum Apo-A1 and TAP on the recurrence after TURBT in patients with bladder cancer. The risk of recurrence in patients with high expression of both was 25.25 times that of patients with low expression of both, and the synergistic effect was 1.521 times that of the sum of the effects of the two alone. In the risk of tumor recurrence, 32.95% was caused by the interaction between the two. Conclusions:The risk of recurrence after TURBT in patients with bladder cancer may be related to the levels of serum Apo-A1 and TAP. Increase of the two levels may be a risk factor for postoperative recurrence, and there is a significant dose-response relationship between the two, and there is a positive interaction with tumor recurrence.

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 investigate the alterations in soft tissue morphology and thickness in the mid-face region of patients with cleft lip and palate (UCLP) secondary to maxillofacial deformity following Le Fort I osteotomy.Methods:A total of 22 patients (16 males and 6 females aged from 17 to 28 years with an average of 20 years) diagnosed with cleft lip and palate secondary to maxillofacial deformity were collected from the Wuhan University Hospital of Stomatology from July 2012 to August 2020. All patients underwent Le Fort I osteotomy. CBCT scans were obtained at T0 (3 days before surgery), T1 (7 days after surgery), and T2 (1 year after surgery). The Dolphin11.95 software and 3D Slicer software were utilized to measure and analyze the soft tissue near the mid-face osteotomy line. Differences in soft tissue thickness before and after surgery were compared.Results:Before and after the operation, the soft tissue thickness at P3, P5, P6, and P8 on the affected side was thicker than that on the healthy side, and the difference was statistically significant, with a P-value of <0.05. At P5, P6, P7, P8, and P9 below the osteotomy line at T2-T0, the degree of postoperative thinning on the affected side was more apparent than that on the healthy side, and there was statistical significance at P6 ( P<0.05). The postoperative soft tissue asymmetry in the Ck region was improved compared with the preoperative one. The preoperative average protruding of the affected side was 0.63 compared with the healthy side, and the postoperative value was 0.17. The preoperative and postoperative Mann-Whitney U tests showed significantly statistical difference. Conclusions:After Le Fort I osteotomy, the facial asymmetry of patients with unilateral cleft lip and palate secondary to maxillofacial deformity is improved. However, there is still a difference in the soft tissue thickness between the healthy side and the affected side, and the change in soft tissue thickness on the affected side is more significant than that on the healthy side.