Background: Modulation of programmed cell death in tumor cells alters the tumor microenvironment and the influx of tumor-infiltrating lymphocytes, and the combination of its inducers and immune checkpoint inhibitors plays a synergistic role in enhancing antitumor effects.Methods: We downloaded the data of clear cell renal cell carcinoma samples from The Cancer Genome Atlas and used a machine learning approach to build a new programmed cell death index (PCDI) through 13 programmed cell death-related genes. Based on PCDI, clinical features, tumor immune microenvironment, chemotherapy response and immunotherapy response were systematically analyzed.Results: PCDI consists of eight programmed cell death-related genes (TBX3, BID, TCIRG1, IDUA, KDR, PYCARD, IFNG and LRRK2). PCDI is a reliable predictor of survival in clear cell renal cell carcinoma patients and has been validated in multiple external datasets. We found that the high PCDI group showed higher levels of immune cell infiltration and better response to immunotherapy compared to the low PCDI group, and PCDI can also be used for prognostic prediction in a variety of cancers other than clear cell renal cell carcinoma. In vitro experiments demonstrated that knockdown of IDUA inhibited the proliferation and migration of clear cell renal cell carcinoma.Conclusions: The PCDI identified in this study provides valuable insights into the clinical management of clear cell renal cell carcinoma by accurately evaluating the prognosis of patients with clear cell renal carcinoma and identifying the patient population that would benefit from immunotherapy.

Metastatic bladder cancer is characterized by its aggressive behavior and complex molecular mechanisms that remain largely undefined. This study explores the therapeutic potential of targeting peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) using liposomal nanoparticles to deliver PGC-1α siRNA to bladder cancer cells. We employed comprehensive transcriptomic, proteomic, and metabolomic analyses to investigate the impact of PGC-1α silencing. Our in vitro results demonstrate that targeting PGC-1α significantly impairs mitochondrial function and disrupts energy metabolism, affecting critical pathways such as glycolysis and the citric acid cycle, as well as altering mRNA nuclear export. In vivo experiments in animal models show that nanoparticles loaded with si-PGC-1α effectively reduce lung metastasis, indicating a significant impact on metastatic progression. These findings highlight PGC-1α as a key regulator of metabolic reprogramming in metastatic bladder cancer and suggest that its inhibition could serve as a promising therapeutic strategy. By elucidating the role of PGC-1α in cancer metabolism, this study provides new insights into the molecular underpinnings of bladder cancer metastasis and offers potential avenues for developing targeted therapies aimed at the metabolic vulnerabilities of this malignancy.

Introduction: Retroperitoneal bronchogenic cyst, typically situated in the subdiaphragmatic region, is a rare congenital benign developmental abnormality arising from dysplasia of the foregut and abnormal budding of the tracheobronchial tree. Due to its low incidence, there are limited reports regarding this condition.Case presentation: Four retroperitoneal bronchogenic cysts near the left adrenal gland were identified without accompanying clinical symptoms. One case was misdiagnosed as an adrenal tumor prior to surgery, while the others were diagnosed as retroperitoneal cysts of uncertain origin. All cases underwent surgical resection, with three being performed laparoscopically and one utilizing robot-assisted techniques. Pathological reports confirmed the diagnosis of bronchogenic cyst in each instance. The prognosis was favorable for all four patients, with no complications or recurrences observed. Additionally, a literature review was conducted, encompassing 82 cases, which revealed similar characteristics and radiological manifestations in the majority of cases.Conclusion: Although retroperitoneal bronchogenic cysts are rare developmental malformations lacking distinctive clinical and radiological features, reported cases exhibit similarities in certain clinical and imaging characteristics. This report offers additional insights into the diagnosis and management of this rare disease. Future reports are essential to enhance understanding of this disease.