ABSTRACT Background The recurrence of immunoglobulin A nephropathy (IgAN) after kidney transplantation (KT) is common and compromises long‐term graft survival; however, the early identification of patients at high risk of recurrence remains a clinical challenge. This study evaluated the roles of serum galactose‐deficient IgA1 (Gd‐IgA1), proliferation‐inducing ligand (APRIL), and B‐cell activating factor (BAFF) in predicting post‐transplant IgAN recurrence. Methods This retrospective case–control study included patients with primary IgAN who underwent KT at the First Affiliated Hospital, Sun Yat‐sen University, from September 2014 to June 2023. Patients were divided into two groups: post‐transplantation IgAN recurrence ( n = 19) and non‐recurrence ( n = 25). Serum levels of Gd‐IgA1, APRIL, and BAFF were measured pre‐transplantation and at 3, 6, 12, 24, and 36 months post‐transplantation. Results Recipients of kidneys from living donors had a significantly higher risk of IgAN recurrence compared with deceased‐donor recipients (odds ratio = 30.6, p = 0.001). Serum Gd‐IgA1 levels showed good discriminative ability for recurrence at 3 months (area under the curve: 0.85, 95% confidence interval: 0.72–0.99) and 6 months (area under the curve: 0.89, 95% confidence interval: 0.76–1.00) after transplantation. Elevated Gd‐IgA1 levels at 3 and 6 months were significantly associated with recurrence in univariate analyses, and remained the only independent predictor in multivariate Cox models. BAFF levels were significantly lower in the recurrence group at 12 months, while APRIL levels did not differ between the groups at any time point. Conclusions Serum Gd‐IgA1 levels could effectively predict IgAN recurrence risk in patients post‐KT.
Multiple myeloma is a malignant tumor of the hematological system. Early diagnosis is difficult, often resulting in detection at an advanced stage, with a poor prognosis. We report a female patient diagnosed with kappa light chain multiple myeloma who initially exhibited generalized muscle aches and bone pain. Comprehensive evaluations, including serum protein electrophoresis, immunofixation electrophoresis, positron emission tomography/computed tomography, bone marrow cell morphology, immunophenotyping of lymphomas, karyotyping of bone marrow chromosomes, gene detection related to multiple myeloma using nextu2010generation sequencing, fluorescence in situ hybridization, pathological evaluation of renal and bone marrow biopsies, and other relevant examinations, confirmed the diagnosis of kappa light chain multiple myeloma. Unfortunately, the diagnosis was made late in the disease course, leading to a poor prognosis, and the patient's family requested treatment discontinuation. Early screening of monoclonal protein is crucial to improve patient outcomes.
Background Nu2010terminal prou2010brain natriuretic peptide (NTu2010proBNP) has shown increasing prognostic value in renal transplant recipients (RTRs). This study aimed to develop and validate a preoperative nomogram incorporating NTu2010proBNP to predict major adverse cardiovascular events (MACEs) in RTRs. Methods A total of 582 eligible RTRs from The First Affiliated Hospital of Sun Yatu2010sen University were enrolled as the training cohort, and 181 RTRs from the Huangpu Branch were included as the validation cohort. The predictive value of NTu2010proBNP was assessed through correlation analyses with other cardiovascular risk factors and by comparing existing risk models with and without NTu2010proBNP. A least absolute shrinkage and selection operator (LASSO)u2010Cox regression approach was used to develop the nomogram, and model performance was rigorously evaluated using receiver operating characteristic curves, concordance index, calibration curves, decision curve analysis, net reclassification improvement, and integrated discrimination improvement. Results The incorporation of NTu2010proBNP significantly improved model performance, leading to the development of a new preoperative nomogram that included NTu2010proBNP, age, body mass index, diabetes, and retransplantation as predictors. This model achieved a 3u2010year area under the receiver operating characteristic curve of 0.838 (95% confidence interval: 0.792u20130.884) and demonstrated good discrimination, calibration, and clinical utility in both cohorts. Furthermore, it showed superior predictive performance compared with existing models, as confirmed by the comprehensive evaluation metrics. Conclusions A preoperative nomogram incorporating NTu2010proBNP demonstrated good predictive performance for MACEs in RTRs and may also serve as an effective means to enhance existing cardiovascular risk prediction models.
This review discusses the potential applications of machine learning, multimodal data integration, and generative artificial intelligence (AI) in the field of kidney transplantation. Effective prediction of allograft survival, postoperative complications, and rejection after kidney transplantation remains a central research challenge. Machine learning has shown considerable potential in predicting postu2010transplant outcomes by analyzing a large amount of clinical data and images. Multimodal data integration improves the accuracy of predictive models by fusing multimodal data from different sources, such as genomic, imaging, and clinical, to support personalized treatment. Generative AI builds upon both of these approaches. Although still in its early stages, generative AI shows great potential for data augmentation, disease simulation, personalized prediction, and education and training. However, the application of these technologies still faces many challenges, such as data insufficiency, limited model generalizability, as well as ethical and regulatory concerns. In the future, further technological innovations and multidisciplinary collaborations are needed to promote the widespread use of these techniques in kidney transplantation.
Endu2010stage kidney disease (ESKD) has become a major global public health challenge, and kidney transplantation is currently the most effective treatment for ESKD. However, the growing severity of the donor organ shortage has severely limited the clinical application of kidney transplantation. As a potential ultimate solution to the organ shortage, kidney xenotransplantation has achieved a series of milestone advances in recent years, driven by breakthroughs in gene editing technology, inu2010depth understanding of the pathological processes underlying xenotransplantation rejection, the development of novel immunosuppressive strategies, and the gradual launch of clinical research. This review systematically elaborates on the latest advances in basic research on kidney xenotransplantation, including the optimization of geneu2010editing technologies for kidney xenotransplantation, the updated understanding and regulatory strategies of immune rejection mechanisms, and the geneu2010editingu2010mediated optimization of immune compatibility.
Pancreatic cancer is a highly fatal disease characterised by a dense stroma and an immunosuppressive microenvironment. Canceru2010associated fibroblasts (CAFs) are the predominant cell type in the tumor microenvironment (TME), displaying high heterogeneity and plasticity. Evidence indicates that CAFs can either promote or suppress tumor progression and formation of an immunosuppressive microenvironment. As CAF metabolism and biological functions have been explored, it became evident that this cell population plays an important role in pancreatic cancer TME heterogeneity. Most reports discussing pancreatic ductal adenocarcinoma plasticity have not focused on CAFs, rather recognizing fibroblasts as a homogeneous community. Thus, a comprehensive review providing an overview of pancreatic cancer TME plasticity based on CAFs would help researchers better interpret and apply previous findings for this disease. Here, we summarize the current knowledge on pancreatic cancer heterogeneity, tumor development, and immune microenvironment focusing on CAFs. We explore how CAFs can metabolically rewire themselves, differentiate into various phenotypes, support tumor development, remodel the extracellular matrix, and communicate with immune cells in the TME. Finally, we discuss current and upcoming antiu2010tumor strategies targeting CAFs.
Alzheimer's disease (AD) is the most common neurodegenerative disease globally and presents a significant challenge to the aging population of China. Early diagnosis and intervention are core to delaying disease progression; however, the early stages of AD manifest in subtle behavioral changes and are difficult to detect. The pathophysiological mechanisms of AD are characterized by amyloid beta (Au03B2) deposition and abnormal tau protein phosphorylation. Current detection methods, such as positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) analysis, are limited in clinical application because of high costs and the invasive nature of CSF collection. Consequently, blood biomarkers of AD are urgently sought because they are minimally invasive and cost effective. Biochemical mass spectrometry methods, such as immunoprecipitationu2010mass spectrometry and liquid chromatographyu2010tandem mass spectrometry can precisely detect lowu2010abundance biomarkers. These platforms boast sensitivities at the femtogram/milliliter level with specificities exceeding 99%, and are capable of simultaneously quantifying multiple markers. For example, the plasma Au03B242/Au03B240 ratio [area under the curve = 0.967] and plasma pu2010tau217 [correlation coefficient with CSF = 0.891] have demonstrated diagnostic performance comparable to PET/CSF but at a fifth to one tenth of the cost, making them viable diagnostic markers for AD. This review examines the significance and the domestic and international research status of AD blood biomarkers based on biochemical mass spectrometry platforms, and outlines the challenges and prospects for their future clinical application.
Background Perioperative use of immune checkpoint inhibitors (ICIs) in patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT) remains controversial, primarily because of concerns regarding allograft rejection. The present study evaluated the safety and potential efficacy of ICIs as a downstaging or bridging therapy prior to LT. Methods This multicenter retrospective analysis included 17 patients with HCC from six Chinese centers who received at least one cycle of preoperative ICI therapy followed by LT. Results The cohort had a mean age of 51.1 u00B1 9.9 years; 94.1% were men. Disease stages were Barcelona Clinic Liver Cancer Stage A (n = 2), B (n = 10), and C (n = 5). All patients received multimodal therapy combining ICIs (sintilimab, n = 13; tislelizumab, n = 2; atezolizumab, n = 1; and pembrolizumab, n = 1) with locoregional and/or systemic treatments. In accordance with the Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 76.5% (13/17), comprising 1 complete response and 12 partial responses. Following LT, all patients received a tacrolimusu2010based immunosuppressive regimen. Over a median followu2010up of 11.4 months, no indications of graft rejection and no tumor recurrence were observed. Conclusion In the study cohort, preoperative ICIu2010based therapy was not associated with an increased risk of rejection, suggesting its shortu2010term safety in the context of LT for HCC. Larger prospective studies are warranted to validate these findings and to further define the efficacy and safety profile of this approach.
Atherosclerosis, a chronic inflammatoryu2013metabolic disorder, remains a leading cause of cardiovascular morbidity worldwide. This review explores the emerging paradigm of nanomedicineu2010based targeting of macrophage immunometabolic reprogramming as a potentially transformative strategy for atherosclerosis treatment. We emphasize innovative approaches such as stimulusu2013responsive nanocarriers (e.g., pHu2010, reactive oxygen speciesu2010, or enzymeu2010activated systems) for spatiotemporal drug delivery and metabolic modulation within plaques, and nanoplatforms for delivering genetic regulators (e.g., small interfering RNA or microRNA) for precise manipulation of key metabolic targets, including 6u2010phosphofructou20102u2010kinase/fructoseu20102,6u2010bisphosphatase 3 (glycolysis) and ATPu2010binding cassette A1 (cholesterol efflux). Despite promising preclinical outcomes, clinical translation faces substantial challenges, including optimizing nanocarrier biocompatibility, achieving subtypeu2010specific targeting amid macrophage heterogeneity, and resolving scalability and standardization issues. Future advancements will require interdisciplinary collaboration integrating immunometabolism, materials science, and artificial intelligence to develop nextu2010generation nanotherapeutics, coupled with robust clinical validation to facilitate their translation into personalized therapies for atherosclerosis.
Calciphylaxis is a rare yet lifeu2010threatening syndrome characterized by vascular calcification and thrombosis, with poorly understood pathogenesis and limited therapeutic consensus, particularly in kidney transplant recipients. We report two cases of calciphylaxis following renal transplantation, diagnosed via a multidisciplinary approach integrating retrospective clinical data, laboratory analyses, imaging studies, and confirmatory histopathological examination of skin biopsies. A standardized treatment protocol centered on intravenous sodium thiosulfate, combined with aggressive wound care and optimization of calciumu2010phosphate homeostasis, resulted in marked clinical improvement. Both patients exhibited resolution of necrotic skin lesions, stabilization of allograft function, and no recurrence during followu2010up. These outcomes underscore the importance of early diagnosis, confirmed by histopathology, and a multimodal therapeutic strategy targeting hyperparathyroidism, mineral dysregulation, and microvascular calcification. Our cases demonstrate that calciphylaxis may resolve with renal function recovery postu2010transplant or sodium thiosulfateu2013based therapy, reinforcing its role in management and urging evidenceu2010based guidelines for this complication in transplant recipients.
