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 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.

Patients with sudden deafness encounter greater psychological challenges and communication barriers after experiencing sudden hearing loss， and traditional medical models often fail to adequately address their unique needs. This paper analyzed the current situation of emotional and behavioral changes in patients with sudden deafness， and the gap between their expectations and the reality of medical care. From the perspective of narrative medicine， the theory and characteristics of the reconstruction of the doctor-patient relationships in patients with sudden deafness were explored. The results showed that narrative medicine can enhance patients’ emotional resonance and understanding， improve the efficiency and quality of doctor-patient communication， promote the formulation of personalized treatment plans， and enhance treatment adherence and satisfaction. Based on these results， strategies and pathways for the reconstruction of doctor-patient relationships for patients with sudden deafness were proposed， including building empathetic bridges and tapping into mechanisms of emotional resonance within narrative medicine； optimizing communication strategies and promoting the application of narrative techniques in doctor-patient dialogues； connecting narrative pathways and advocating the exploration of stories and strategies in personalized treatments； as well as facilitating treatment adherence and making full use of the psychodynamic effects of narrative medicine. Narrative medicine， as a patient-centered medical practice， can effectively promote the reconstruction of doctor-patient relationships， enhance treatment effectiveness， and offer a more humane treatment experience 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

Abstract: Heterologous boost COVID-19 vaccination can solved the problem of decreased efficacy caused by single dose of vaccine. Heterologous booster with adenoviral-vectored COVID-19 vaccine (Ad5-nCoV) following primary immunization with inactivated COVID-19 vaccines is a widely-used vaccination strategy in clinic, while different routes of Ad5-nCoV administration exist and pose a question which route could be more optimal. In this study, we comprehensively evaluated and compared the vaccine immunity induced in mice immunized according to three different vaccination regimens: “3×phosphate buffered solution(3× PBS)”, “2×inactivated vaccine + 1×inactivated vaccine (3×INA)”, “2×inactivated vaccine + 1×Ad5-nCoV (intramuscular)[2×INA+Ad5(im)]”and“2×inactivated vaccine + 1×Ad5-nCoV (intranasal)[2×INA+Ad5(in)]”. We found that heterologous booster with Ad5-nCoV, irrespective of the route of administration, induced significantly higher levels of anti-Spike IgG and subclasses (IgG1and IgG2c), Spike-specific T cells, class-switched Spike+ memory B cells (MBCs) than homologous booster with 3rd dose of inactivated COVID-19 vaccine. Of note, compared with the intramuscular given, intranasal given of Ad5-nCoV as a booster dose clearly induced higher levels of serum and bronchoalveolar bavage fluid anti-spike immunoglobulin A, and moreover, induced stronger infiltration of major innate effector cells like neutrophils, natural killer cells and dendritic cells into the lung tissue, which suggested that mucosal vaccine responses are generated upon intranasal booster with Ad5-nCoV. Altogether, our study analyzed the vaccine immunity induced by different COVID-19 vaccines administered using different regimens, which may guide the clinical use of other types of prophylactic vaccines aiming to mount improved vaccine responses.

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 explore the relationship between family intergenerational contact, depressive symptoms and self-rated health status in the elderly, so as to provide insights into promoting health of the elderly and actively coping with population aging. Methods: Demographic information, intergenerational contact frequency, self-rated health status and depressive symptoms in the elderly at ages of 65 years and older were collected through the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Structural equation model was established to analyze the effects of intergenerational contact on self-rated health and the mediating role of depressive symptoms between family intergenerational contact and self-rated health in the elderly. Results: Totally 15 497 elderly participants were enrolled, with 6 727 males (43.41%) and 8 770 females (56.59%), and there 12 583 individuals lived with family members (81.19%). The median age was 85.00 (interquartile range, 16.00) years. The scores of self-rated health and depressive symptoms were (3.39±0.87) and (2.22±0.56), respectively. The results of structural equation model analysis showed that after adjusting for age, gender and residence, frequent intergenerational contact had a direct positive effect on self-rated health (effect size=0.038, P<0.001), and could improve the depressive symptoms (effect size=0.089, P<0.001) in the elderly. In addition, depressive symptoms had a negative effect on self-rated health in the elderly (effect size=-0.422, P<0.001). Conclusions Frequent intergenerational contact can improve the self-rated health status in the elderly, and indirectly improve the self-rated health level by alleviating depressive symptoms.

Objective:To investigate the risk factors of hematoma enlargement or rebleeding in the short term after decompressive craniectomy in patients with cerebral hemorrhage.Methods:The clinical data of 209 cerebral hemorrhage patients underwent decompressive craniectomy from January 2019 to October 2021 in the Second Affiliated Hospital of Zhejiang University and Keqiao District Traditional Chinese Medicine Hospital of Shaoxing City were retrospectively analyzed. According to the head CT result at the time of consultation and 24 h after the onset, the patients were divided into hematoma enlargement and rebleeding group (group A, 28 cases), hematoma enlargement group (group B, 47 cases), rebleeding groups (group C, 13 cases), non-hematoma enlargement and non-rebleeding group (group D, 121 cases). The gender, age, body mass index, time of first CT examination, first bleeding volume, admission Glasgow coma score (GCS), admission systolic pressures, admission diastolic pressure, admission activated partial thromboplastin time (APTT), admission alanine aminotransferase (ALT), admission white blood cell count, hematoma site, broken into the ventricle, irregular hematoma, timing of operation, maximum body temperature of 24 h after admission, intraoperative hemostasis and unsatisfactory on postoperative blood pressure control were collected. Multifactor Logistic regression analysis was used to analyze the independent risk factors of hematoma enlargement or rebleeding in the short term after decompressive craniectomy in patients with cerebral hemorrhage.Results:There were no statistical difference in sex composition, age and body mass index among 4 groups ( P>0.05). The incidences of admission systolic pressures ≥140 mmHg (1 mmHg = 0.133 kPa), admission diastolic pressure ≥90 mmHg, admission APTT≥37 s, admission ALT≥40 U/L, admission white blood cell count ≥10 × 10 9/L, admission GCS, maximum body temperature of 24 h after admission ≥ 37 ℃, first bleeding volume ≥ 60 ml, time of first CT examination ≥3 h, time from onset to operation ≥ 12 h, irregular hematoma, hematoma in the thalamus, broken into the ventricle, intraoperative hemostasis, unsatisfactory on postoperative blood pressure control in group A were significantly higher than those in group B, group C and group D: 92.86% (26/28) vs. 55.32% (26/47), 7/13 and 23.97% (29/121); 89.29% (25/28) vs. 51.06% (24/47), 6/13 and 17.36% (21/121); 92.86% (26/28) vs. 48.94% (23/47), 6/13 and 14.88% (18/121); 78.57% (22/28) vs. 42.55% (20/47), 5/13 and 16.53% (20/121); 89.29% (25/28) vs. 53.19% (25/47), 7/13 and 18.18% (22/121); 89.29% (25/28) vs. 57.45% (27/47), 7/13 and 23.14% (28/121); 92.86% (26/28) vs. 55.32% (26/47), 7/13 and 23.97% (29/121); 85.71% (24/28) vs. 48.94% (23/47), 6/13 and 16.53% (20/121); 89.29% (25/28) vs. 53.19% (25/47), 7/13 and 23.14% (28/121); 89.29% (25/28) vs. 44.68% (21/47), 6/13 and 17.36% (21/121); 96.43% (27/28) vs. 51.06% (24/47), 7/13 and 22.31% (27/121); 67.86% (19/28) vs. 46.81% (22/47), 6/13 and 20.66% (25/121); 89.29% (25/28) vs. 42.55% (20/47), 6/13 and 18.18% (22/121); 92.86% (26/28) vs. 53.19% (25/47), 7/13 and 20.66% (25/121); 89.29% (25/28) vs. 48.94% (23/47), 6/13 and 16.53% (20/121), the incidences in group B and group C were significantly higher than those in group D, and there were statistical differences ( P<0.05); there were no statistical differences in the incidences between group B and group C ( P>0.05). Multifactor Logistic regression analysis result showed that maximum body temperature of 24 h after admission ≥ 37 ℃, time from onset to operation ≥12 h, hematoma in the thalamus, intraoperative hemostasis and unsatisfactory on postoperative blood pressure control were the independent risk factors of hematoma enlargement or rebleeding in the short term after decompressive craniectomy in patients with cerebral hemorrhage ( OR = 3.271, 25.739, 4.255, 3.995 and 13.749; 95% CI 1.072 to 9.977, 7.711 to 85.919, 1.297 to 13.954, 1.252 to 12.747 and 3.961 to 47.732; P<0.05 or <0.01). Conclusions:After decompressive craniectomy, some patients with cerebral hemorrhage may have hematoma enlargement or rebleeding in the short term. The admission body temperature, hematoma site, intraoperative hemostasis, postoperative blood pressure control and operation timing are influencing factors, and the corresponding intervention may help to prevent the occurrence of hematoma enlargement or rebleeding in a short term.

Objective:To explore the clinical value of introducing 68Ga PSMA PET / CT into the prostate cancer(PCa)screening clinic, and to analyze the incidence rate and biopsy of PCa in the screening clinic of our hospital. Methods:The data of the people who participated in PCa screening in the urology screening clinic of our hospital from March 2021 to November 2021 were retrospectively analyzed. Serum PSA was used as the screening index. The subjects with PSA≥4ng/ml were first examined by mpMRI to find suspicious nodules, and the positive ones were further examined by 68Ga-PSMA PET/CT to determine the lesions.The puncture target was outlined, and systematic+ targeted puncture was conducted under ultrasound guidance. The age, PSA distribution, puncture detection rate, Gleason score and clinical stage of patients with PCa were recorded. Results:A total of 1 079 subjects were included in the screening, with an average age of (63.9±9.9)(ranging 40-92) years old, and 249 patients (23.1%, 249/1 079) with PSA≥4ng/ml. Among them, 87 cases (87/249, 34.9%) received mpMRI, and 34 cases (34/249, 13.7%) had PI-RADS score ≥3 points. These 34 patients with suspected nodules on MRI were further scanned with 68Ga-PSMA PET/CT, and 11 cases (11/249, 4.4%) had abnormal uptake of PSMA nuclide. A total of 32 patients (12 patients with PSA abnormalities and 20 patients with positive imaging) finally received prostate biopsy, and 11 patients were diagnosed with PCa, with a positive detection rate of 34.4% (11/32), accounting for 1.0% (11/1 079) of the screening population. Among them, 20 patients with positive imaging (9 patients with only mpMRI positive and 11 patients with both mpMRI and 68Ga-PSMA PET/CT positive) underwent system + targeted fusion biopsy, and the positive rate was 45% (9/20). 12 patients (only PSA abnormal) underwent routine systematic puncture biopsy, and the positive detection rate was 16.7% (2/12). The difference between the two groups was statistically significant ( P<0.05). Among the patients with confirmed PCa, 27.3% (3/11) had Gleason score less than 7, and 72.7% (8/11) had Gleason score≥7. Localized PCa (≤T 2) accounted for 45.4% (5/11), local progression (T 3-T 4) accounted for 18.2% (2/11), and metastatic PCa suggested by 68Ga-PSMA PET/CT accounted for 36.4% (4/11), including 3 systemic multiple bone metastases and one bone metastasis with distant lymph node metastasis. Clinically significant PCa accounted for 90.9% (10/11) of the confirmed patients, and the proportion of high-risk patients in localized or locally advanced PCa was 71.4% (5/7). Conclusions:In PCa screening, if 68Ga-PSMA PET/CT is introduced on the basis of conventional mpMRI, the detection rate of clinically meaningful PCa can be improved. Combined with targeted puncture, tumor lesions can be found early and the screening efficiency of PCa can be improved. In this study, the detection rate of PCa in outpatient screening reached 1.0%. In confirmed cases, the proportion of high-risk patients and metastatic patients was higher.