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.

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 The aim of this study is to analyze the prevalence of depression and anxiety symptoms and its relationship with the socio-economic position(SEP)among the elderly people in Dai rural areas of Jinggu County,Yunnan province.Methods A multi-stage stratified random sampling method was used to conduct a questionnaire survey among 1409 people aged 60 and over in Dai rural areas of Jinggu County,Yunnan Province.The individual SEP index was constructed using the principal component analysis.Results The prevalence of anxiety symptoms,depression symptoms,and mixed anxiety-depressive disorder symptoms was 4.8%,52.0%,and 4.2% among them,2.6%,49.4%,and 2.3% among the males,and 6.8%,54.5%,and 6.0% among the females respectively.Females had the higher prevalence of anxiety symptoms and mixed anxiety-depressive disorder symptoms than males(P<0.05).Elderly people with the higher level of education,annual per capita household income and SEP had the lower prevalence of anxiety symptoms and mixed anxiety-depressive disorder symptoms than their counterparts(both P<0.05).The prevalence of depression symptoms increased with age(P<0.01).The difference in the prevelence of depression symptoms among the elderly people with the different numbers of chronic conditions was statistically significant(P<0.01).The results of multivariate logistic regression analysis showed that the elderly people with lower SEP were more likely to suffer from the anxiety symptoms(OR=0.707,95% CI:0.566～0.883),depression symptoms(OR=0.492,95% CI:0.438～0.552),and mixed anxiety-depressive disorder symptoms(OR=0.602,95% CI:0.469～0.773).Conclusion There are significant socio-economic differences in the prevalence of anxiety symptoms and depression symptoms among the elderly people in Dai rural areas of Jinggu County,Yunnan province.Future mental health interventions should more focus on females,elderly people with advanced age,multiple chronic diseases and low SEP,so as to reduce the occurrence of depression symptoms and anxiety symptoms.

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.

Brucellosis is a zoonotic disease caused by Brucella. Its typical clinical manifestations include fever, chills, fatigue, bone and muscle pain, etc. Brucellosis can affect multiple organs and tissues, of which spine is the most common affected part, forming Brucella spondylitis. Due to the clinical manifestations and imaging characteristics of infected individuals being similar to other spinal diseases, it is easy to cause misdiagnosis, missed diagnosis, and mistreatment. This article reviews the latest research progress in clinical manifestations, imaging examination, diagnosis, differential diagnosis, and treatment of Brucella spondylitis both domestically and internationally, in order to provide reference for the diagnosis and treatment of Brucella spondylitis.

Objective:To evaluate the effects of opioid-sparing analgesia on the incidence of sepsis in severely burned patients in the retrospective cohort study.Methods:The clinical data from patients with severe burns admitted to three teaching hospitals in Guangdong from 2011 to 2020 were retrospectively extracted and analyzed. The patients were divided into 2 groups based on the analgesic regimen within 30 days after injury: continuous opioids analgesia group (continuous opioid infusion at a relative constant rate for more than 72 h) and opioid-sparing analgesia group (patient-controlled intravenous analgesia/intermittent administration/opioid-free analgesia). Patient′s age, severity of burn, inhalation injury and basal pain score at rest were matched by the propensity score at a 1∶1 ratio. The primary outcome measure was the occurrence of sepsis within 90 days of admission. Secondary outcome measures included 30-day and 90-day all-cause mortality, clinical diagnosis of multiple organ dysfunction syndrome, and prevalence of burn wound infection. The amount of opioid used was also recorded.Results:A total of 328 severely burned patients were finally enrolled, with 145 patients in continuous opioid analgesia group and 183 patients in opioid-sparing analgesia group, and 110 pairs of patients (220 cases) were finally matched by the propensity score.Compared with continuous opioid analgesia group, the total consumption of opioid, daily consumption per analgesia, and consumption per burn area were significantly decreased, and the incidence of sepsis and wound infection was decreased( P<0.05), and no significant change was found in the incidence of multiple organ dysfunction syndrome, 30-day and 90-day all-cause mortality in opioid-sparing analgesia group( P>0.05). Conclusions:Compared with the continuous opioid analgesia regimen, opioid-sparing analgesia can reduce the risk of sepsis in severely burned patients.

Objective:To investigate the effect of Enolase inhibition (ENOblock) on autophagy- related protein expression and motor function promotion after spinal cord injury in rats.Methods:A total of 160 female SD rats were divided into sham-operation group, 3-methyladenine (3-MA) autophagy inhibitor treatment group (3-MA group), spinal cord injury group and ENOblock treatment group (ENOblock group) according to the random number table, with 40 rats per group. Back laminectomy without injury to the spinal cord was performed in sham-operation group. Spinal cord injury at T 8 was induced by using a modified Allen weight-drop apparatus to establish a spinal cord injury model in the rest three groups. 3-MA and ENOblock groups were injected 3-MA (2.5 mg/kg) and ENOblock (100 μg/kg) into the caudal vein immediately after injury, respectively. Sham-operation and spinal cord injury groups were injected same dose of isotonic sodium chloride solution into the caudal vein. At 1, 3, 7, 14 and 21 days after injury, BBB score was used to evaluate lower limb motor function. At day 3 after injury, the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II to LC3-I and protein expressions of autophagy effector protein (Beclin-1) and polyubiq-uitinbinding protein (p62) were detected by Western blotting. At day 7 after injury, LC3-Ⅱ and Beclin-1 positive cells in the injured area of the spinal cord were determined by immunofluorescence staining. At day 3 after injury, the mRNA expressions of Beclin-1 and Enolase in the injured area of the spinal cord were detected by RT-PCR. Results:At 1, 3, 7, 14 and 21 days after injury, BBB score was lowered in 3-MA group [(1.4±1.1)points, (2.4±0.9)points, (3.8±1.8)points, (7.6±1.1)points, (9.0±2.1)points], spinal cord injury group [(0.8±0.5)points, (1.8±0.9)points, (3.6±0.9)points, (6.2±1.3)points, (8.0±0.7)points] and ENOblock group [(2.0±0.9)points, (2.2±0.8)points, (4.8±1.1)points, (10.6±1.5)points, (13.2±0.8)points] compared to sham-operation group [(21.0±0.0)points at all time points] (all P<0.05). Moreover, the score in ENOblock group was significantly higher than that in spinal cord injury group at 14, 21 days after injury, and the score in 3-MA group was significantly higher than that in spinal cord injury group at day 21 after injury (all P<0.05). At day 3 after injury, Western blotting showed that the ratio of LC3-II to LC3-I and protein expressions of Beclin-1 and p62 were 0.46±0.10, 0.41±0.03, 0.81±0.03 in sham-operation group, 0.66±0.06, 0.69±0.02, 0.59±0.05 in 3-MA group, 0.85±0.06, 1.07±0.03, 0.41±0.02 in spinal cord injury group and 0.68±0.06, 0.66±0.08, 0.55±0.02 in ENOblock group. By comparison, spinal cord injury group showed significantly higher ratio of LC3-II to LC3-I and protein expression of Beclin-1 and significantly lower protein expression of p62 than sham-operation group (all P<0.05); 3-MA and ENOblock groups showed significantly lower ratio of LC3-II to LC3-I and protein expression of Beclin-1 and significantly higher protein expression of p62 than spinal cord injury group (all P<0.05); there was no significant difference in the ratio of LC3-II to LC3-I and protein expressions of Beclin-1 and p62 between 3-MA and ENOblock groups (all P>0.05). At day 7 after injury, immunofluorescence staining showed that LC3-II and Beclin-1 positive cells in 3-MA and ENOblock groups were less than those in spinal cord injury group. At day 3 after injury, RT-PCR showed that mRNA expressions of Beclin-1 and Enolase in spinal cord injury group (1.08±0.16, 0.98±0.17) were higher than those in sham-operation group (0.25±0.06, 0.29±0.03). Moreover, mRNA expressions of Beclin-1 and Enolase in 3-MA group (0.77±0.11, 0.72±0.04) and ENOblock group (0.81±0.10, 0.64±0.09) were lower than those in spinal cord injury group (all P<0.05). There was no significant difference in mRNA expressions of Beclin-1 and Enolase between 3-MA and ENOblock groups (all P>0.05). Conclusions:Autophagy activity is significantly up-regulated after spinal cord injury in rats. ENOblock can inhibit autophagy and promote motor function recovery in rats by regulating the expression of autophagy-related proteins.

Objective:To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis.Methods:The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ 2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result:Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III–IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ 2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ 2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ 2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ 2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ 2=6.293, P=0.043). The proportions of TNM Stage III–IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ 2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ 2=13.994, P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ 2=10.457, P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ 2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ 2=5.086, P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ 2=19.791, P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ 2=4.601, P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ 2=11.996, P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ 2=7.643, P=0.006), had a higher proportion of TNM Stage III–IV disease (60.2% [100/166] vs. 24.2% [8/33], χ 2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ 2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively ( P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS ( P=0.026). Conclusions:Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.