Objective: To investigate the effects of clinical routine X-ray irradiation dose (average irradiation dose: 29.7±0.54 Gy) on the function, apoptosis, activation state and mitochondrial function of platelets during in vitro storage, so as to provide experimental evidence for optimizing platelet irradiation strategies. Methods: A paired experimental design was adopted. Platelets were collected from 12 healthy donors, and each sample was equally divided into the irradiated group and the control group (non-irradiated). All samples were stored for 5 days under standard platelet preservation conditions (22±2℃, continuous oscillation). Flow cytometry was used to detect platelet count, apoptosis rate (Annexin V+ positive rate), activation markers (CD62P, PAC-1, CD42b) and reactive oxygen species (ROS) level. Meanwhile, mitochondrial-specific probes were used to evaluate changes in mitochondrial count, membrane potential and adenosine triphosphate (ATP) content. Additionally, transmission electron microscopy (TEM) was employed to observe the ultrastructure of platelets, with a focus on mitochondrial morphology, platelet membrane integrity and granule distribution. Results: Within 5 days of storage, the platelet count was (841±89.16)×10 /L in the irradiated group and (824.5±92.88)×10 /L in the control group, with no statistically significant difference between the two groups (P=0.54). The apoptosis rate was (4.94±1.39) % in the irradiated group and (5.50±0.83) % in the control group, showing no significant difference (P=0.31). For activation indicators, the CD62P expression rate was (24.32±7.57) % in the irradiated group versus (25.21±8.13) % in the control group (P=0.43). The PAC-1 positive rates were (12.15±4.43) % and (11.75±3.40) % in the irradiated group and control group, respectively (P=0.44). The CD42b expression rates were (12.14±4.43) % and (11.75±3.4) % in the two groups, respectively (P=0.47). The ROS levels were (31.98±8.1) % and (30.64±5.89) % in the two groups, respectively (P=0.45). No significant differences were found in the above indicators. For mitochondrial function indicators, the mitochondrial count was (55.88±11.49) % in the irradiated group and (53.5±7.24) % in the control group (P=0.57). The ATP contents were (42.45±5.29) % and (41.58±9.50) % in the irradiated group and control group, respectively (P=0.77). The relative membrane potential values were (59.53±10.89) % and (57.49±6.54) % in the two groups, respectively (P=0.47). No significant difference were observed on the mitochondrial function-related indicators. TEM further confirmed that the ultrastructure of platelets in the irradiation group was intact, the mitochondrial morphology was normal, and no pathological changes such as swelling or vacuolization were observed. Conclusion: This study evaluated the impact of conventional-dose X-ray irradiation on platelet storage quality, confirming that this dose does not significant impair platelet count, apoptosis rate, activation status, or mitochondrial function. This finding provides important experimental evidence for the clinical promotion of X-ray irradiation technology and suggests its potential as a safe alternative to γ irradiation. Future studies could further expand the sample size and extend the observation period to verify the effects of X-ray irradiation on long-term platelet storage and post-transfusion in vivo survival rate.

[摘 要] 目的：探讨异位表达血红蛋白亚基（HBA/HBB）对缺氧条件下嵌合抗原受体T细胞（CAR-T细胞）功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法：全基因合成技术合成靶向HER2的CAR序列，构建共表达HBA或HBB的CAR慢病毒载体，包装慢病毒后感染人原代T淋巴细胞，制备异位表达HBA/HBB的CAR-T细胞，命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况，采用细胞计数板计数检测细胞增殖水平，通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力，qPCR检测CAR-T细胞中缺氧诱导因子-1α（HIF-1α）表达水平，利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果：不同细胞构建的实体瘤模型均存在明显缺氧情况，且CAR-T细胞浸润水平与缺氧程度呈显著负相关（P < 0.000 1）。HBA CAR-T与HBB CAR-T构建成功（阳性率 > 60%），相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降，增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞（均P < 0.05）。HBA CAR-T与HBB CAR-T内HIF-1α表达降低（均P < 0.001），且缺氧程度显著降低（均P < 0.001）。结论：异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。

Objective To investigate the diagnosis and treatment of 2 cases with spontaneous renal vascular rupture, and discuss the possible causes and treatment methods of this disease. Methods The clinical data and treatment methods of the 2 patients with spontaneous renal vascular rupture treated with renal artery embolization in Universal Global Xi'an Beihuan Hospital were analyzed. Relevant literature was reviewed to summarize the possible causes of this condition. Results The patients had no obvious history of trauma and no obvious abnormal coagulation function, and sought treatment due to sudden lumbar and abdominal pain. Laboratory tests revealed significantly decreased hemoglobin level, and elevated blood glucose (27.8, 27.6mmol/L). Abdominal computed tomography (CT) indicated perirenal hematoma and active bleeding. The bleeding arteries were located at the terminal branches of the anterior renal artery. Precise embolization was performed using CT angiography and selective renal artery angiography plus embolization, achieving an immediate hemostasis success rate of 100%. Postoperative hemoglobin level stabilized, and follow-up CT scans showed significant absorption of the perirenal hematoma without significant deterioration of renal function. Based on literature review and case analysis, the possible cause of spontaneous renal vascular rupture in these two patients was renal vascular sclerosis due to long-term diabetes. Other common etiologies of this condition included renal tumor, vascular malformation, and hypertension. Conclusion Spontaneous renal vascular rupture is rare. Renal artery embolization, as aminimally invasive treatment, can effectively control bleeding and protect renal function. The specific pathogenesis of this condition still requires further investigation. Long-term diabetes mellitus with poor blood glucose control may be associated factors, but more evidence is needed.

Objective To explore the feasibility of magnetic compression technique (MCR) in the treatment of severe single mid-ureteral stricture in a rabbit model. Methods After 10 female New Zealand rabbits were selected, the distal end of the right ureter was ligated with silk thread. Two weeks after the operation, when the right ureter was dilated, the mid-ureter was ligated again with silk thread to create a severe single mid-ureteral stricture animal model. Longitudinal incisions were made at the upper and lower ends of the ligation site, and cylindrical NdFeB magnets with central holes (sub-magnets and main magnets) were placed to anastomose and recanalize the mid-ureteral stricture. The magnets were adjusted to the appropriate position to automatically align and attract each other. The longitudinal incision sites of the ureter were sutured with 6-0 Prolene thread, and the abdominal cavity was closed layer by layer. The operation time was recorded. X-ray films were taken every two days to confirm the position of the magnets and record the time of magnet detachment. Three weeks after the operation, the anastomotic specimens were obtained, and the formation of the anastomosis was evaluated with gross observation and histological staining. Results Two weeks after ligation, all experimental rabbits showed obvious dilation of the right ureter. The mid-ureteral ligation and placement of the male and female magnets were successfully completed in all 10 experimental rabbits, with an operation time of (24.00±5.15)minutes. The male and female magnets attracted each other well. X-ray examination showed that the magnets detached and entered the distal ureter (14.0±1.9) days after magnetic compression. The recanalization of the severe single mid-ureteral stricture was successfully achieved. The gross specimens and histological examination of the anastomosis showed that the anastomosis remained patent and the mucosal healing was good. All experimental rabbits survived well after the operation without serious complications. Conclusion MCT provides a new idea and novel method for the treatment of mid-ureteral stricture. This study confirmed the feasibility of this technique in treating severe single mid-ureteral stricture in a rabbit model. The operation is relatively simple and has potential for clinical application.

Objective To fabricate a large-diameter vascular graft with a pore size gradient structure mimicking that of natural blood vessels, using poly-L-lactic acid (PLLA) and polycaprolactone (PCL) as base materials through electrospinning and ultrasonic pore-forming techniques, and to evaluate its application potential. Methods A three-layered tubular graft was fabricated from a PCL/PLLA blend (mass ratio 6 : 4) via electrospinning, followed by an ultrasonic pore-forming process to create a gradient porosity. The resulting graft (diameter: 2 cm, length: 4 cm) was implanted into the descending thoracic aorta of an experimental pig using an end-to-end anastomosis. Graft patency and anastomotic sites were monitored by computed tomography angiography (CTA) at 1 and 6 weeks post-surgery. After 2 months, the graft was explanted for systematic evaluation of vascular regeneration and repair through gross examination, histopathology (H&E and elastic fiber staining), immunohistochemistry [for ETS-related gene (ERG), Actin, and Vimentin], and scanning electron microscopy (SEM). Results Postoperative CTA confirmed excellent graft patency at both 1 and 6 weeks, with no evidence of thrombosis or anastomotic stenosis. Gross examination of the 2-month explant revealed a smooth luminal surface covered by neotissue. Histopathological analysis demonstrated that the graft successfully induced the formation of a three-layered structure resembling a native vessel wall, comprising endothelial cells, smooth muscle cells, and fibroblasts. Immunohistochemistry further verified coverage of the luminal surface by endothelial cells (ERG-positive), along with the presence of neosmooth muscle (Actin-positive) and fibroblasts (Vimentin-positive). Endothelial cells were observed adhering to the inner surface of the artificial vessel under SEM. Conclusion The biomimetic, three-layered PLLA/PCL large-diameter vascular graft, constructed via electrospinning and ultrasonic pore-forming, exhibits excellent short-term patency and biocompatibility in a large animal model. More importantly, it demonstrates a significant potential to promote host cell infiltration and achieve in situ regeneration of a three-layered vascular wall structure, providing a promising experimental basis for the development of next-generation functional vascular substitutes.

[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.

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

Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.
Humans ; Large Language Models ; Tomography, X-Ray Computed

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Objective To analyze the burden and epidemic trends of gastric cancer in China from 1990 to 2021, and to provide a scientific basis for the formulation of effective prevention and control strategies. Methods　Data from the 2021 Global Burden of Disease (GBD) database were used to extract the number of the incidence, prevalence, and death cases, as well as the disability-adjusted life years (DALY) for gastric cancer in China from 1990 to 2021. The corresponding crude rates and age-standardized rates were calculated. The Joinpoint regression model was employed to analyze the trends in the burden of gastric cancer, and a comprehensive examination was conducted from multiple dimensions including age, gender, and time. Results From 1990 to 2021, the age-standardized incidence rate (ASIR) of gastric cancer in China decreased from 48.03 per 100,000 to 29.05 per 100,000, the age-standardized prevalence rate (ASPR) decreased from 67.17 per 100,000 to 57.23 per 100,000, the age-standardized mortality rate (ASMR) decreased from 46.05 per 100,000 to 21.51 per 100,000, and the age-standardized DALY rate (ASDR) decreased from 1181.61 per 100,000 to 501.26 per 100,000. The AAPCs of ASIR, ASPR, ASMR, and ASDR were -1.61%, -0.50%, -2.44%, and -2.75%, respectively. The incidence, prevalence, mortality and DALY rates showed a trend of increasing first and then decreasing with age. Although females had higher incidence, prevalence, mortality, and DALY numbers in the older age groups, males exhibited higher crude rates across all age groups. Conclusion　The overall disease burden of gastric cancer in China showed a downward trend from 1990 to 2021, and men and middle-aged and elderly people are the key populations for prevention and control efforts.