Xiao Li

Renal artery aneurysm and renal vein aneurysm are rare vascular lesions, and their coexistence within the same kidney poses considerable diagnostic and surgical challenges. We report a 51-year-old woman presenting with recurrent left flank and back pain. Computed tomography angiography demonstrated a 2.1-cm upper-pole renal artery aneurysm arising from a terminal intrarenal arterial branch and a 3.0-cm renal vein aneurysm arising from a large intrarenal venous tributary in the mid-pole renal sinus. Nephrectomy had been recommended at another institution because of the anatomical complexity, but the patient strongly wished to preserve the affected kidney. She underwent single-port retroperitoneoscopic excision of both aneurysms, with closure of the terminal arterial stump, primary closure of the venous wall defect, and renorrhaphy. The operative time was 95 min, warm ischemia time was 20 min, and estimated blood loss was 30 mL. Histopathological examination confirmed the diagnoses. At 4 months after surgery, color Doppler ultrasonography demonstrated preserved main left renal arterial flow and intrarenal arterial perfusion without Doppler evidence of hemodynamically significant main renal artery stenosis. Dedicated renal venous Doppler assessment and differential renal function testing were not performed. This case demonstrates that single-port retroperitoneoscopic kidney-sparing excision can be performed in selected patients with concomitant intrarenal arterial and venous aneurysms.

Prostate cancer (PCa) exhibits an immune “cold” tumor microenvironment (TME) with significant enrichment of immunosuppressive myeloid-derived suppressor cells (MDSCs), which contribute to tumor progression and poor responses to immune checkpoint blockade (ICB). Although extensively studied, the precise mechanism underlying the tumor-intrinsic signals that educate and sustain the expansion and immunosuppressive function of MDSCs remains unelucidated. Here, we identify a previously unrecognized function of RelB by which nuclear interaction with ILF2 restricts ubiquitin-mediated degradation and sustains nuclear stability of RelB, thereby enhancing RelB-mediated CSF2 transactivation and enhanced GM-CSF (granulocyte-macrophage colony-stimulating factor) production and secretion. The secreted GM-CSF, in turn, promotes RelB nuclear accumulation, forming a feed-forward loop for sustaining GM-CSF generation. In MDSCs, GM-CSF activates STAT3-mediated MDSC expansion and immunosuppression. Disruption of RelB/ILF2 complex attenuates GM-CSF-driven MDSC expansion, restores CD8⁺ T cell-mediated antitumor activity, and inhibits tumor growth. In addition, a RelB-targeting peptide SN52 sensitizes PCa tumors to PD-1 blockade therapy. Collectively, our findings identify the RelB/ILF2–GM-CSF loop as a central regulator of MDSC-mediated immunosuppression, which may be targeted to improve PCa response to ICB.

Early screening and targeted intervention can effectively reduce cancer burden. However, most studies have proposed polygenic risk score (PRS) to perform risk prediction and population risk stratification. In this study, we investigate the causal links and shared genetics between cancer and metabolic traits to map the onco-metabolic nexus. Using multivariable Cox models, we assessed 240 trait–cancer associations. Genomic analyses included genome-wide and local genetic correlations and genomic structural equation modeling (gSEM) to identify pathways linking metabolic traits to cancer. We then used Deterministic Bayesian Sparse Linear Mixed Model (DBSLMM) to build both single and integrative PRS models based on gSEM and compared their predictive performance. Most of the metabolic traits are risk factors to cancer, such as waist–hip ratio–colorectal cancer [hazard ratio (HR) = 1.34; 95% confidence interval (CI) = 1.23–1.46; P = 1.59 × 10−11]. In the genetic correlation analysis, we identified 41 significant pairs in the onco-metabolic nexus and 405 significant genomic regions. Mendelian randomization analysis revealed 17 significant causal pairs. The integrative PRS model combining gSEM for metabolic traits improved prediction, with 13.95% variance explained in kidney cancer. The study highlights the intertwined genetic and clinical relationships between cancers and metabolic traits, improving cancer screening and intervention. Significance: By uncovering the shared genetic basis of cancer and metabolic traits, our work enables a novel integrative risk prediction model, which promises to enhance precision screening and targeted prevention strategies for high-risk populations.

Immunotherapy has achieved limited efficacy in prostate cancer (PCa), largely due to its profoundly immunosuppressive tumor microenvironment (TME). However, the metabolic mechanisms underpinning this immune resistance remain poorly defined. Here, we identify lactate dehydrogenase A (LDHA)-driven lactate metabolism as a critical regulator of myeloid-derived suppressor cell (MDSC) activation in PCa. Integrated metabolomic, single-cell, and spatial transcriptomic analyses revealed that LDHA is highly expressed in PCa malignant epithelial cells and correlates with increased lactate production and immune exclusion. LDHA-high tumors exhibited enriched infiltration of polymorphonuclear MDSCs (PMN-MDSCs), which were spatially co-localized with LDHA-positive tumor regions. Mechanistically, lactate uptake through monocarboxylate transporter 1 (MCT1) enhanced PMN-MDSC differentiation and upregulated Arg1 and NOS2, reinforcing T cell suppression. Genetic ablation of LDHA in murine models markedly reduced PMN-MDSC infiltration, restored CD8⁺T cell activity, and inhibited tumor growth. Pharmacological inhibition of LDHA with FX-11 synergized with anti-PD-L1 therapy, producing durable tumor regression. Collectively, these findings define LDHA-driven lactate metabolism as a key metabolic checkpoint in PCa immune evasion and provide a rationale for combining LDHA inhibition with immune checkpoint blockade to overcome immunotherapy resistance.

R-loops are dynamic nucleic acid structures implicated in genome regulation and instability, yet their contributions to the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remain unclear. Here, we integrated publicly available ccRCC transcriptomic and clinical datasets to quantify R-loop-associated activity using single-sample gene set enrichment analysis (ssGSEA) and develop a prognostic model using linear machine-learning algorithms. R-loop activity was elevated in advanced disease and associated with unfavorable outcomes. Among R-loop-related genes, ACACA was prioritized for its dominant contribution across multiple linear prognostic models, alongside its strong association with metabolic reprogramming. Single-cell transcriptomics showed relatively high ACACA expression in malignant cells that functioned as communication hubs with lipid metabolism-related signaling, and spatial transcriptomics confirmed preferential enrichment of ACACA within malignant regions. In vitro and xenograft experiments further demonstrated that ACACA promoted proliferation and migration and suppressed apoptosis, accompanied by reduced R-loop accumulation, enhanced fatty acid metabolism and improved mitochondrial function. Together, these findings identify ACACA as an R-loop-associated metabolic driver connecting genomic stress with lipid reprogramming and TME remodeling in ccRCC, supporting its potential as a prognostic biomarker and therapeutic target.

Background: Metastasis is the primary cause of mortality in patients with prostate cancer (PCa), yet effective treatments remain scarce. Identifying reliable biomarkers and understanding their underlying mechanisms is crucial for advancing clinical management. Methods: Firstly, we integrated single-cell and bulk transcriptomic data and employed the Scissor tool to characterize tumor cells with metastatic advantages (termed metastatic cells). Then, independent predictive genes for metastasis were identified through univariate and multivariate regression analyses. The role of hub genes in PCa metastasis was further validated using multiple large datasets, malignant phenotype experiments, in vivo metastatic models, and a clinical-sample-based immunohistochemical cohort. Further, we explored the metabolic characteristics related to hub genes through unbiased functional annotation, and validated the upregulated glycolysis by measuring l -lactic acid production, extracellular acidification rates (ECAR), and oxygen consumption rates (OCR). Finally, multi-omics data were employed to investigate the promoter-methylation-dependent regulation of alpha-2-glycoprotein 1 ( AZGP1 ) transcription, with methylation confirmed through PCa cell-based methylation-specific PCR (MSP) assays. Results: AZGP1 was identified as an independent protective predictor of metastasis, which was validated in vitro and in vivo. Metabolic functional annotation revealed that glycolysis was upregulated in AZGP1 -positive luminal cells. Consistently, overexpression of AZGP1 in PCa cells was associated with lower l -lactic acid levels, reduced ECAR, and increased OCR. In addition, DNA methylation at the cg26429636 region was linked to decreased transcriptional expression of AZGP1 . MSP assays revealed an unmethylated pattern in PCa cells with high AZGP1 expression, and higher methylation levels in AZGP1 -low cells. Conclusions: Promoter methylation of AZGP1 leads to reduced transcriptional expression, thereby promoting glycolysis in tumor cells and facilitating metastasis. The detection of AZGP1 methylation levels offers a valuable reference for dynamic surveillance of PCa metastasis.

Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has posed a significant burden on affected individuals and healthcare systems. While pharmacological treatments are commonly used, non-pharmacological management strategies have gained attention for their potential benefits in improving CP/CPPS symptoms. However, the comparative efficacy of these non-pharmacological interventions remains unclear. The aim of this study is to assess the comparative effectiveness of non-pharmacological interventions for CP/CPPS regarding prostatic symptoms. Method This systematic review and network meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search will be conducted in electronic databases, including PubMed, Embase, Cochrane Library and Web of Science, to identify relevant studies. Eligible studies will include randomised controlled trials investigating non-pharmacological management strategies for CP/CPPS. Two independent reviewers will screen the retrieved citations, extract data and assess the risk of bias. Data synthesis will involve performing a network meta-analysis to compare the efficacy of different non-pharmacological interventions while considering both direct and indirect evidence. Ethics and dissemination The review does not require ethical approval. The findings of the review will be disseminated through publication in an academic journal, presentations at conferences and various media outlets. PROSPERO registration number CRD42024506143.

Background: Although RANK‐LRANK interaction is essential for osteoclastogenesis, the mechanisms by which cancer cells invade bone tissues and initiate osteolytic metastasis remain unclear. Here, we show that the hyperactivation of RelB fosters prostate cancer (PCa) osteolytic metastasis by coordinating interleukin‐8 (IL‐8) and calcium‐binging protein A4 (S100A4).Methods: The factors promoting PCa bone metastasis were investigated in sera from PCa patients and tumour tissues derived from nude mice using immunohistochemical analysis and enzyme‐linked immunosorbent assays (ELISA). Cell mobility and mineralization were quantified using BioStation CT and Osteolmage assay. The relative cistrome was investigated in advanced PCa cells by standard transcriptional analyses, including the luciferase reporter response, site‐directed mutagenesis, and chromatin immunoprecipitation (ChIP) assay. PCa cell‐initiated tumour formation, expansion, and bone metastasis were validated in mice using multiple approaches, including orthotopic, intraskeletal, and caudal arterial implantation models.Results: IL‐8 and S100A4 correlated with patient Gleason scores and bone metastasis. RelB upregulated IL‐8, facilitating androgen receptor (AR)‐independent growth. RelB‐Sp1 interaction enhanced epithelial‐mesenchymal transition (EMT) by activating Snail and Twist. RelB‐NFAT1c super‐enhancer upregulated S100A4 in the organization of the cytoskeleton and bone metastasis. The RelB‐IL‐8‐S100A4 signalling axis was confirmed to promote osteolytic metastasis in nude mice.Conclusion: RelB‐IL‐8 reciprocally promoted EMT by activating inflammatory signalling and inactivating AR signalling. IL‐8 is essential for provoking PCa metastasis but insufficient to drive bone metastasis. IL‐8‐S100A4 cooperation was necessary for metastatic cells to target the bone.Highlights: RelB activates inflammatory signalling by upregulating IL‐8 and suppressing AR. RelB upregulates S100A4 by cooperating with NFATC1. IL‐8 boosts EMT by activating Snail 1 and Twist 1, and S100A4 exacerbates osteolytic metastasis via calcium consumption. RelB harnesses IL‐8 and S100A4 to drive PCa osteolytic metastasis.

Background: Hot flashes are the common and debilitating symptom among prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT). Strong evidence from multiple rigorously designed studies indicated that pharmacological option such as venlafaxine provides partial relief, but the tolerability is poor when dose is not tapered. Hence, alternative therapy is needed. Previous studies reported that acupuncture may be helpful in the management of hot flashes. However, the insufficient randomized controlled trial limited the quality of evidence. Methods: Five hospitals will recruit 120 acupuncture naïve patients with moderate-to-severe hot flashes after prostate cancer received ADT in China from February 2023 to December 2024. Participants will be randomly 2:1:1 allocated to the 18 sessions of verum acupuncture at true acupuncture points plus usual care, 18 sessions of non-penetrating sham acupuncture at non-acupuncture points plus usual care, or usual care alone over 6 weeks. The primary outcome measure is the change of mean weekly hot flashes symptom severity score (HFSSS) at the end of treatment compared with baseline. Expected Results and Conclusion: We will be able to measure the effectiveness of acupuncture for patients with PCa suffering from ADT-induced hot flashes and whether acupuncture is superior to sham acupuncture and usual care. The proposed acupuncture treatment might provide an alternative option for those patients. Trial Registration: Clinicaltrials.gov (NCT05069467).

It has been reported that heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) is highly expressed in prostate cancer (PCa) and associated with poor prognosis of patients with PCa. Nevertheless, the specific mechanism underlying HNRNPA2B1 functions in PCa remains not clear. In our study, we proved that HNRNPA2B1 promoted the progression of PCa through in vitro and in vivo experiments. Further, we found that HNRNPA2B1 induced the maturation of miR-25-3p/miR-93-5p by recognizing primary miR-25/93 (pri-miR-25/93) through N6-methyladenosine (m⁶A)-dependent manner. In addition, both miR-93-5p and miR-25-3p were proven as tumor promoters in PCa. Interestingly, by mass spectrometry analysis and mechanical experiments, we found that casein kinase 1 delta (CSNK1D) could mediate the phosphorylation of HNRNPA2B1 to enhance its stability. Moreover, we further proved that miR-93-5p targeted BMP and activin membrane-bound inhibitor (BAMBI) mRNA to reduce its expression, thereby activating transforming growth factor β (TGF-β) pathway. At the same time, miR-25-3p targeted forkhead box O3 (FOXO3) to inactivate FOXO pathway. These results collectively indicated that CSNK1D stabilized HNRNPA2B1 facilitates the processing of miR-25-3p/miR-93-5p to regulate TGF-β and FOXO pathways, resulting in PCa progression. Our findings supported that HNRNPA2B1 might be a promising target for PCa treatment.