T-cell therapy,as an emerging strategy for bladder cancer treatment,primarily includes tumor-infiltrating lymphocyte(TIL)therapy,T cell receptor-engineered T-cell(TCR-T)therapy,and chimeric antigen receptor T-cell(CAR-T)therapy.TIL therapy involves extracting,expanding,and reinfusing tumor-infiltrating T cells,aiming to promote tumor regression,which has achieved initial progress in the field of bladder cancer.TCR-T therapy involves genetically modifying T cells to specifically recognize tumor antigens presented by MHC,with clinical trials targeting NY-ESO-1 and other targets progressing in an orderly manner.CAR-T therapy utilizes artificially designed CAR molecules to target bladder cancer-highly expressed antigens such as prostate-specific membrane antigen(PSMA)and human epidermal growth factor receptor 2(HER2),with multiple studies confirming its potent cytotoxic effects.This article systematically summarizes the existing research,advantages and limitations of T-cell therapy in bladder cancer,so as to provide reference for exploring new options for the next-generation immunotherapy strategies of bladder cancer.

T-cell therapy,as an emerging strategy for bladder cancer treatment,primarily includes tumor-infiltrating lymphocyte(TIL)therapy,T cell receptor-engineered T-cell(TCR-T)therapy,and chimeric antigen receptor T-cell(CAR-T)therapy.TIL therapy involves extracting,expanding,and reinfusing tumor-infiltrating T cells,aiming to promote tumor regression,which has achieved initial progress in the field of bladder cancer.TCR-T therapy involves genetically modifying T cells to specifically recognize tumor antigens presented by MHC,with clinical trials targeting NY-ESO-1 and other targets progressing in an orderly manner.CAR-T therapy utilizes artificially designed CAR molecules to target bladder cancer-highly expressed antigens such as prostate-specific membrane antigen(PSMA)and human epidermal growth factor receptor 2(HER2),with multiple studies confirming its potent cytotoxic effects.This article systematically summarizes the existing research,advantages and limitations of T-cell therapy in bladder cancer,so as to provide reference for exploring new options for the next-generation immunotherapy strategies of bladder cancer.

In recent years,patient-derived tumor organoid(PDTO)models have rapidly emerged as important tools in cancer research,thanks to their unique ability to preserve the characteristics of primary tumors.These models provide a reliable preclinical research platform for screening individualized chemotherapy and targeted therapies for patients.However,traditional PDTOs lack immune cells and cannot replicate the tumor immune microenvironment,which restricts their utility in evaluating immunotherapies.To address this challenge,researchers have developed composite models that incorporate both tumor cells and immune cells,known as patient-derived immunocompetent tumor organoids(PDITOs).PDITOs have shown excellent performance in the preclinical evaluation of immunotherapies,particularly with PD-1/PD-L1 immune checkpoint inhibitors,with some studies reporting up to 100％accuracy in predicting patient responses to immunotherapy.As a common malignancy of the urinary system,bladder cancer has benefited from the application of PDITOs in drug screening and personalized immunotherapy evaluation,demonstrating significant potential.This paper aims to review the rise and development of PDITOs,and compare the advantages and limitations of using different methods to construct PDITOs,so as to explore their application in the treatment of bladder cancer.

High-risk non-muscle invasive bladder cancer (HR-NMIBC) is associated with a higher risk of recurrence and progression. The standard treatment involves intravesical Bacillus Calmette-Guérin (BCG) instillation following transurethral resection of the bladder cancer. However, in cases of BCG unresponsiveness, radical cystectomy is typically recommended. Due to the high complication rates and significant impact on quality of life associated with this procedure, bladder-preserving treatment (BPT) strategies have emerged as an alternative. This review summarizes recent advances in BPT, including combined chemoradiotherapy, immune checkpoint inhibitors, targeted therapies, localized precision treatments, and novel immunomodulators. With ongoing technological and therapeutic innovations, BPT has become an effective alternative for patients who are unable or unwilling to undergo surgery, reshaping the treatment landscape of HR-NMIBC.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

High-risk non-muscle invasive bladder cancer (HR-NMIBC) is associated with a higher risk of recurrence and progression. The standard treatment involves intravesical Bacillus Calmette-Guérin (BCG) instillation following transurethral resection of the bladder cancer. However, in cases of BCG unresponsiveness, radical cystectomy is typically recommended. Due to the high complication rates and significant impact on quality of life associated with this procedure, bladder-preserving treatment (BPT) strategies have emerged as an alternative. This review summarizes recent advances in BPT, including combined chemoradiotherapy, immune checkpoint inhibitors, targeted therapies, localized precision treatments, and novel immunomodulators. With ongoing technological and therapeutic innovations, BPT has become an effective alternative for patients who are unable or unwilling to undergo surgery, reshaping the treatment landscape of HR-NMIBC.

This study summarizes the preoperative and intraoperative nursing experience in 5 cases of bridge-to-transplant heart transplantation with left ventricular assist device(LVAD)explant.Key points of nursing include:preoperative care and assessment of LVAD patients,preoperative discussion of the multidisciplinary team,safe transfer of patients to surgical rooms and other preoperative preparation,cardiomyocardial protection and multidisciplinary team cooperation during bridging transplantation,and intra-operative patient safety management.All 5 patients in this group successfully completed the surgery and were discharged.Pressure sores,wound infections,and other postoperative complications have not occurred.Postoperative cardiac function of 5 patients in this group were classified as New York Heart Association class Ⅰ～Ⅱ.The follow-up period for the 5 patients in this group ranged from 6 months to 6 years.The results of the most recent echocardiography follow-up showed that the left ventricular ejection fraction of all patients was all above 65％,with well prognosis.

This study summarizes the preoperative and intraoperative nursing experience in 5 cases of bridge-to-transplant heart transplantation with left ventricular assist device(LVAD)explant.Key points of nursing include:preoperative care and assessment of LVAD patients,preoperative discussion of the multidisciplinary team,safe transfer of patients to surgical rooms and other preoperative preparation,cardiomyocardial protection and multidisciplinary team cooperation during bridging transplantation,and intra-operative patient safety management.All 5 patients in this group successfully completed the surgery and were discharged.Pressure sores,wound infections,and other postoperative complications have not occurred.Postoperative cardiac function of 5 patients in this group were classified as New York Heart Association class Ⅰ～Ⅱ.The follow-up period for the 5 patients in this group ranged from 6 months to 6 years.The results of the most recent echocardiography follow-up showed that the left ventricular ejection fraction of all patients was all above 65％,with well prognosis.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.