BackgroundAlthough fungal infections are relatively rare, they have low detection rates and high mortality rates. The value of metagenomic next-generation sequencing (mNGS) in kidney transplant patients with fungal infections remains insufficiently explored, especially regarding diagnosis and antimicrobial stewardship.MethodsFrom September 2021 to August 2023, 234 kidney transplant patients were enrolled, with detailed data collected on 66 patients suspected of fungal infections. The pathogen detection performance of mNGS and conventional microbiological tests (CMTs) was compared. The impacts of mNGS and CMTs on treatment adjustment were also assessed. Finally, the value of mNGS in detecting donor-derived infections was investigated.ResultsAmong 66 patients, 21 fungal species were identified: 18 species detected by mNGS and 10 by CMTs. The overall positive rate of mNGS was significantly higher than culture (90.67% vs. 26.67%), especially for multiple fungal infections (9vs0). mNGS identified more Candida (26vs12), Pneumocystis jirovecii (14vs0), Aspergillus (10vs4), Mucor (6vs2) organisms compared with CMTs. Donor-derived fungi were identified in 11 (6.7%) patients, including 10 cases of Candida spp. and 1 case of Mucor spp. Anti-infection therapies were adjusted in 28 (24.4%) cases based on mNGS.ConclusionThe mNGS technique showed distinct advantages in detecting fungal infections in kidney transplant patients, facilitating informed anti-infection strategies and enhanced graft protection. Moreover, it provides effective identification of fungal infections originating from donor sources.

Purpose:To systematically evaluate the safety boundaries of holmium laser application during ureteroscopy by quantifying thermal dose and to explore the detailed repair mechanisms of the ureter and kidneys following injury. Methods:Twelve female piglets were selected. Key variables included holmium laser power, irrigation flow rates (0, 7.5, 15 mL min-1), and fluid temperatures. Thermal dose was calculated as Cumulative Equivalent Minutes at 43 °C (CEM43). Trauma and repair processes were assessed via microscopic imaging, Masson staining, and immunohistochemistry for inflammatory and fibrosis markers. Statistical analyses were performed using two-way analysis of variance (ANOVA). Results:At an irrigation flow rate of 15 mL min-1, the temperature rise was minimal with a negligible thermal dose (CEM43 < 1), ensuring safety even at 30 W. In contrast, compromised irrigation (7.5 mL min-1) or no-flow conditions resulted in rapid heat accumulation, with CEM43 values reaching extreme levels (>1013) at high powers. In the kidneys, the repair process involved a transition from inflammation to fibrosis over time, which was correlated with an M1-to-M2 macrophage polarization. Crucially, anatomical ureteral stricture was observed only when the laser-induced injury involved ≥3/4 of the ureteral circumference. Conclusion:Sufficient irrigation is critical to maintain thermal safety. While thermal exposure induces fibrotic changes driven by macrophage polarization, mechanical injury extent (≥3/4 circumference) appears to be the dominant predictor for the formation of ureteral stricture. These findings emphasize the importance of maintaining high-flow irrigation and minimizing extensive circumferential damage during surgery.

Perirenal adipose tissue (PAT) is implicated in inflammatory responses, yet its potential value in predicting systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL) remains underexplored. This study evaluated the predictive role of perirenal fat characteristics for post-PCNL SIRS. A retrospective analysis included clinical data from 723 patients undergoing PCNL.Patients were stratified into non-SIRS (n = 592) and SIRS (n = 131) groups based on postoperative outcomes. PAT imaging characteristics were extracted from imaging databases. Clinical characteristics and biochemical parameters were compared. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for variable selection, and logistic regression was employed to develop a risk model. Model performance was evaluated using receiver operating characteristic (ROC) analysis. Subgroup analyses and interaction tests were conducted to assess model stability. Calibration curves and internal bootstrap validation (1,000 resamples) were applied to evaluate model reliability. LASSO regression confirmed six facto: Urine nitrite(NIT), Hydronephrosis, Operation time, Lateral Perirenal Fat Thickness(LPrFT); Posterior Perirenal Fat thickness(PPrFT); The ratio of perirenal fat area to renal parenchyma area(PFA/RPA ratio). The multivariate logistic model demonstrated strong discriminative ability (AUC = 0.827,95

Intracellular proton-coupled electron transfer (PCET) governs cellular metabolism and fate, and its dysregulation is closely associated with disease progression. In normal cells, PCET into the electron transport chain supports ATP production and cellular growth. In cancer cells, however, overexpressed lactate dehydrogenase (LDH) redirects PCET to pyruvate, producing lactate and thereby sustaining tumor growth, proliferation, and metastasis. Reprogramming LDH-driven PCET in living tumors therefore represents an attractive antitumor strategy, yet no artificial catalyst has been shown to outcompete LDH and reprogram PCET in living cells. Here, we report an organoiridium catalyst, IrIII(Cp*)-CN, that captures proton-coupled electrons from NADH and transfers them to protons to generate H2 under ultrasound irradiation at physiological pH. In living cancer cells, IrIII(Cp*)-CN outcompetes LDH and redirects LDH-driven pyruvate reduction and lactate production toward proton reduction and H2 generation. This PCET-reprogramming process converts a tumor-promoting, lactate-producing reaction into a tumor-suppressive, H2-generating reaction, suppressing lactate and ATP production and markedly inhibiting tumor growth with minimal toxicity to normal cells and tissues. These findings establish a framework for reprogramming intracellular PCET via artificial catalysts that outcompete endogenous enzymes, offering a strategy for treating diseases associated with dysregulated cellular redox metabolism.

The present study investigates how Sirtuin 1 (SIRT1) regulates the worsening of calcium oxalate (CaOx) crystal-induced mitochondrial dysfunction and fibrosis in the kidneys with age. To establish a CaOx crystal deposition model, glyoxylic acid (Gly) was injected intraperitoneally into both young and aged mice. Additionally, an in vitro model was created by stimulating human renal tubular epithelial (HK2) cells with D-galactose (D-gal) and calcium oxalate monohydrate (COM). Lipid deposition, mitochondrial function, and fibrosis levels were assessed using various techniques, including western blotting (WB), polymerase chain reaction (PCR), immunohistochemistry, immunofluorescence, and specific staining methods. The effects on lipid deposition, mitochondrial function, and fibrosis were further analyzed by manipulating the expression of SIRT1 and peroxisome proliferator-activated receptor (PPAR-α), both in vitro and in vivo. Aging exacerbates the kidney mitochondrial dysfunction and fibrosis induced by CaOx crystals, with SIRT1 playing a crucial regulatory role in this process. SIRT1 regulates lipid metabolism via PPARα, intensifying the aging-related kidney mitochondrial damage and fibrosis induced by CaOx crystals.

Background:Kidney stones are widely considered a disease closely related to systemic metabolic disorders and systemic inflammation. The apolipoprotein B to albumin ratio (ApoB/Alb ratio) is a novel comprehensive biomarker that combines atherogenic lipid levels with systemic nutritional and inflammatory status. This study integrated data from two independent cohorts to explore the association between the serum ApoB/Alb ratio and the risk of kidney stones in adults. Methods:The Chinese single-center retrospective cohort included 741 subjects (223 kidney stone patients and 518 healthy controls) evaluated from March 2022 to September 2025. For external validation, 12,108 adult participants from the US National Health and Nutrition Examination Survey (NHANES) database (2007-2016) were included. Multivariate logistic regression analysis evaluated the independent association, while restricted cubic spline (RCS) smoothing curve fitting explored the dose-response relationship. Results:In the Chinese cohort, the serum ApoB/Alb ratio in the kidney stone group was significantly higher than in the control group (1.92 ± 0.52 vs. 1.84 ± 0.47, P = 0.048). After adjusting for comprehensive confounding factors, an elevated ApoB/Alb ratio was identified as a significant risk factor for kidney stones (OR = 3.26, 95% CI: 1.98-5.38). This significant positive association was highly consistent in the US NHANES validation cohort (OR = 1.30, 95% CI: 1.06-1.58). RCS analysis revealed a continuous positive linear dose-response relationship between the ApoB/Alb ratio and the prevalence of kidney stones in both cohorts. Furthermore, sensitivity and subgroup analyses demonstrated that this predictive value remains robust and is largely independent of traditional metabolic comorbidities such as hypertension and diabetes. Conclusion:As a comprehensive indicator of lipid metabolic disorders and inflammatory/nutritional imbalance, the ApoB/Alb ratio serves as a novel, highly sensitive, and reliable biomarker for predicting kidney stone risk.

The increasing global prevalence of nephrolithiasis represents a significant public health concern. However, the role of environmental contaminants such as glyphosate remains unclear. Herein, epidemiological analysis, network toxicology, and experimental validation were integrated to investigate this association. Cross-sectional analysis of NHANES data demonstrated a significant dose-dependent relationship between urinary glyphosate levels and nephrolithiasis prevalence. Each unit increase in log-transformed glyphosate concentration was associated with a 25% increase in nephrolithiasis risk (OR = 1.25, 95% CI: 1.06-1.47). Network toxicology combined with molecular docking and dynamics simulations identified the PI3K/AKT signaling pathway as a potential target, showing stable binding of glyphosate to core proteins. This mechanism was functionally validated in vivo and in vitro, indicating that glyphosate co-exposure exacerbated calcium oxalate-induced renal tubular injury, oxidative stress, and apoptosis through suppression of the PI3K/AKT pathway. This effect was significantly reversed by pathway agonism. Collectively, this study provides the first integrative evidence identifying environmental glyphosate exposure as a novel risk factor for nephrolithiasis. Furthermore, inhibition of the PI3K/AKT pathway was delineated as the primary underlying mechanism, offering a conceptual framework for future preventive and therapeutic strategies.

Calcium oxalate (CaOx), the primary constituent of most urinary calculi, triggers inflammatory responses and tissue damage upon entry into renal tubules, playing a pivotal role in nephrolithiasis pathogenesis. Salidroside (SAL), a phenolic glycoside isolated from Rhodiola plants, exhibits diverse pharmacological activities. This study integrated network pharmacology with experimental validation to investigate the therapeutic potential and mechanistic basis of SAL against urinary stones. In both in vitro and in vivo models of CaOx crystal-induced kidney injury, SAL treatment markedly reduced renal crystal deposition, inflammatory cascades, and associated histological impairments. Network pharmacology analysis suggested the involvement of PANoptosis, a finding subsequently confirmed through experimental assays as the central mechanism underpinning SAL-mediated protection. Molecular docking and further experimental verification indicated that SAL directly engages with core components of the PANoptosome complex. These results collectively demonstrate that SAL mitigates nephrolithiasis-related renal injury and inflammation primarily through suppression of PANoptosis.

BackgroundClear cell renal cell carcinoma (ccRCC) frequently exhibits transcriptional reprogramming driven by oncogenic C-Myc. Fibrillarin (FBL), a nucleolar C-Myc target, is markedly upregulated in ccRCC, correlating with poor prognosis and essential for tumor cell survival.MethodsIntegrated single-cell RNA sequencing, bulk transcriptomics, and proteomics were used to identify FBL as a key target. Functional assays, immunoprecipitation-mass spectrometry, and molecular docking were performed to investigate FBL's oncogenic mechanisms and interaction with TRIM21.ResultsFBL promotes ccRCC cell proliferation, migration, and tumor growth via PI3K/AKT pathway activation. TRIM21 was identified as a novel FBL-binding E3 ubiquitin ligase that catalyzes K48-linked polyubiquitination of FBL at lysine 292, accelerating its proteasomal degradation. TRIM21 overexpression reduces FBL levels, inhibits PI3K/AKT signaling, and reverses FBL-induced oncogenic phenotypes. TRIM21 is downregulated in ccRCC tissues and associated with unfavorable prognosis.ConclusionsThe TRIM21-FBL axis regulates ccRCC progression by modulating PI3K/AKT signaling, providing mechanistic insight and potential therapeutic targets for ribosome biogenesis and oncogenic signaling.

Surface-enhanced Raman spectroscopy (SERS) is a highly sensitive and selective analytical technique that has shown great potential in bioanalysis. However, due to the relatively large size of protein molecules, steric hindrance can impede target molecules from entering hotspot regions, leaving most analytes at SERS-inactive regions and thereby reducing detection sensitivity and signal reproducibility. In this work, we designed an open, tip-enhanced V-shaped nanocavity array formed by an ordered bilayer of gold nanotetrahedra to enable SERS detection of osteopontin, a biomarker for urinary calculi. A finite element multiphysics simulation was used to elucidate the distributions of electric field enhancements and hydrodynamic processes in solution and air of the nanocavity arrays. The results show that during solvent evaporation, the V-shaped geometry guides and traps osteopontin molecules at the upper and lower tip regions of the nanocavity where the electric field is enhanced, achieving a synergistic effect between localized high field enhancement at the tips and hydrodynamic enrichment. Protein-size-dependent experiments showed that the nanocavity preferentially detects proteins whose dimensions match the cavity scale while exhibiting limited response to larger proteins. Further application to clinical urine sample analysis identified characteristic fingerprint peaks of osteopontin in samples from urolithiasis patients, enabling preliminary discrimination between healthy controls and patients with urinary calculi. Therefore, this tip-enhanced V-shaped nanocavity provides a new approach for the noninvasive detection of urolithiasis biomarkers and offers a valuable solution to the challenge of SERS detection of large molecules.

Kidney stones, as prevalent crystalline disorders within the urinary system, pose significant clinical challenges due to their high incidence and recurrence rates. The lack of clear pathological mechanisms has limited therapeutic options to surgical interventions without effective preventive strategies. In this study, integrated in vitro and in vivo models revealed that calcium oxalate (CaOx) exposure induced concurrent accumulation of LC3B-II and p62 autophagy markers. Blockade of autophagic flux at the late stage was validated via mCherry-GFP-LC3 dual fluorescence assays, demonstrating impaired autolysosome formation. Mechanistically, autophagic flux obstruction triggered oxidative stress, apoptosis, and proinflammatory cascades, collectively exacerbating renal tubular injury. Pharmacological inhibition of autophagy initiation with 3-methyladenine (3-MA) disrupted the maladaptive autophagy-reinforcement cycle, improving cellular viability and renal function. Conversely, lysosomal acidification blockade via bafilomycin A1 (BafA1) failed to mitigate cytotoxicity. Molecular screening identified specific downregulation of VAMP7-a SNARE complex component critical for autophagosome-lysosome fusion-as the primary mediator of CaOx-induced fusion defects. Overexpression of VAMP7 restored autophagic homeostasis and attenuated crystallotoxicity. This work pioneers a phase-specific autophagy targeting strategy: either suppression of pathological autophagic overactivation or restoration of terminal fusion machinery effectively alleviates CaOx nephrotoxicity. These findings provide a mechanistic foundation for precision therapeutics in stone disease management.

BACKGROUND: Circular RNAs (circRNAs) constitute a recently discovered class of evolutionarily conserved and robust regulatory RNAs. Their potential as diagnostic biomarkers and therapeutic targets for various diseases is a subject of growing interest. Nevertheless, the precise regulatory roles and underlying mechanisms of circRNAs in the context of kidney stone formation remain largely unexplored. METHODS: Utilizing RNA high-throughput sequencing technology and quantitative real-time polymerase chain reaction (qRT-PCR), we conducted a comprehensive screen for calcium oxalate crystals (CaOx)-induced differential expression of circular RNA (circRSPRY1) in the human renal tubular epithelial cells (HK-2) kidney injury model. Subsequently, we employed a combination of RNA and protein expression analyses, luciferase activity assays, and immunohistochemistry (IHC) to elucidate the regulatory role of circRSPRY1 in targeting the miR-21-5p/PTEN axis, influencing the processes of necroptosis and apoptogenesis. RESULTS: In this investigation, we observed a notable downregulation of circRSPRY1 expression in both the CaOx-stimulated HK-2 renal tubular epithelial cell injury model and a glyoxalate-induced mouse model of renal calcinosis. Notably, overexpressing circRSPRY1 led to reduced crystalline deposition in our in vitro model. Mechanistically, circRSPRY1 overexpression was associated with the downregulation of cleaved-caspase-8, p-MLKL, P-RIPK1, and P-PIPK3 levels, consequently inhibiting necrotic apoptosis. Furthermore, circRSPRY1 appeared to act as a miR-21-5p sponge, resulting in reduced miR-21-5p availability for PTEN binding and, subsequently, increased PTEN expression, thus impeding the progression of necrotic apoptosis and kidney injury. Additionally, inhibiting miR-21-5p levels demonstrated the ability to suppress necrotic apoptosis in renal calcinosis by downregulating the PTEN/MLKL pathway. CONCLUSION: Our findings suggest that circRSPRY1 represents a novel candidate circRNA implicated in the pathogenesis of kidney stones. circRSPRY1 acts as a sponge, sequestering miR-21-5p to modulate PTEN expression, thereby regulating necrotic apoptosis and contributing to the formation of calcium oxalate stones.

Purpose Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic syndrome characterized by lower urinary tract symptoms, yet its pathogenesis and diagnostic markers remain unclear. Methods Bladder mucosal tissues from 10 IC/BPS patients and 11 controls underwent whole transcriptome sequencing. Differentially expressed genes and their biological functions were analyzed using GO, KEGG, GSEA, and WGCNA. Hub genes (CCL8, MMP25, PLP1) were validated by internal samples and an external dataset (GSE11873). Immune infiltration was assessed via ssGSEA, and LASSO regression identified hub genes. Results Differentially expressed genes in IC/BPS were enriched in cytokine receptor binding and extracellular matrix synthesis pathways. Increased infiltration of central memory CD8 + T cells (Tcm CD8 + cells) was observed. CCL8, MMP25, and PLP1 were significantly associated with IC/BPS. Conclusion The pathogenesis of IC/BPS may be related to the activation of cytokine receptor binding pathways and the upregulation of Tcm CD8 + cells via CCL8-dependent regulation. This provides new targets and directions for future basic and clinical studies of IC/BPS.

This study aimed to develop interpretable machine-learning models to predict the risk of metabolic syndrome-kidney stone disease (MetS-KSD) comorbidity based on dietary micronutrient intake. Using data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, 54 candidate features, including dietary variables and demographic covariates, were incorporated into the analysis. Six mainstream machine-learning models, including Random Forest, XGBoost, LightGBM, k-nearest neighbors, support vector machine, and Naïve Bayes, were evaluated using a comprehensive multi-metric framework incorporating the area under the receiver operating characteristic curve (AUC-ROC), area under the precision-recall curve (AUC-PR), accuracy, F-beta score, sensitivity, and specificity. SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) were applied to enhance model interpretability. A total of 4936 participants were included, representing approximately 4,597,435 U.S. adults with MetS-KSD comorbidity after application of sampling weights. After variance inflation factor analysis and Boruta feature selection, 33 features were retained, including 25 dietary micronutrients and 8 demographic variables. When demographic and dietary variables were jointly modeled, Random Forest demonstrated the best performance (AUC-ROC = 0.958; AUC-PR = 0.961). When models were constructed using dietary micronutrients alone, XGBoost achieved optimal performance (AUC-ROC = 0.956; AUC-PR = 0.960). SHAP and LIME analyses identified lycopene, added vitamin B12, magnesium, dietary fiber, theobromine, and vitamin K as key contributing features, with importance rankings varying according to demographic context. Supplementary sensitivity analyses further supported model robustness and the effectiveness of SMOTE-based imbalance correction. These findings suggest that interpretable machine learning may provide a useful framework for nutritional risk stratification in MetS-KSD comorbidity, although external validation in independent populations is still required.

This study investigated the association between serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and kidney stone formation in adults using two independent datasets. A hospital-based cross-sectional cohort included 757 participants (229 stone cases and 528 controls) from March 2022 to September 2025, with clinical data on blood biochemical markers and histories of hypertension and diabetes collected for analysis. Between-group comparisons were conducted using chi-square or Kruskal–Wallis tests, and the association between sdLDL-C and kidney stones was examined through multivariable logistic regression, subgroup analyzes. To evaluate the robustness and generalizability of the findings, data from 9,721 adults in the 2007–2016 National Health and Nutrition Examination Survey (NHANES) were also analyzed. In the Chinese cohort, higher sdLDL-C concentrations were independently associated with a lower risk of kidney stones (OR = 0.53, 95% CI: 0.38–0.74), with a non-linear inverse dose–response pattern. The NHANES cohort showed similar results, revealing a negative and linear association between sdLDL-C and stone risk (OR = 0.68, 95% CI: 0.50–0.91). Subgroup analyzes indicated that the protective association was most evident among individuals over 40 years and in both sexes in the Chinese cohort, whereas in NHANES it was more pronounced among participants aged 20–39 or 60–85 years and among females. These findings suggest that sdLDL-C is inversely associated with kidney stone risk across populations; however, prospective studies are required to determine causality.

Objective: The optimal surgical approach for 1.0-2.0 cm renal stones in solitary kidney patients remains controversial. This retrospective study compared mini-percutaneous nephrolithotomy (mPCNL) and flexible ureteroscopy (f-URS) outcomes in this vulnerable population. Methods: Between June 2018 and April 2024, 50 patients with solitary kidneys and 1.0-2.0 cm renal stones underwent either mPCNL (n = 26) or f-URS (n = 24). Outcomes included 3-month stone-free rate (SFR), complications (Clavien-Dindo classification), and renal function (serum creatinine, eGFR by CKD-EPI equation) at the baseline, 72 h, and 1 month. Results: Stone-free rates were comparable (mPCNL 96.2% vs. f-URS 91.7%, p = 0.157). The f-URS group demonstrated significantly less hemoglobin decline (2.2 ± 0.9 vs. 5.7 ± 2.4 g/dL, p < 0.001) and shorter hospitalization (4.1 ± 1.1 vs. 7.8 ± 1.6 days, p < 0.001). All Grade II complications (8.3%, requiring transfusion) occurred in the mPCNL group. At 1 month, serum creatinine decreased more with f-URS (15.4 ± 7.96 vs. 8.7 ± 4.23 μmol/L, p < 0.001), with greater eGFR improvement (16.7 ± 4.7 vs. 15.4 ± 5.2 mL/min/1.73 m2, p = 0.023). Conclusions: In this retrospective cohort, f-URS achieved comparable stone clearance to mPCNL alongside a superior early safety profile and better short-term renal functional preservation. These preliminary findings suggest that f-URS represents a viable nephron-sparing option for this high-risk population. However, these results are considered hypothesis-generating, and further prospective, long-term studies are required to evaluate the durability of these functional benefits.

Abstract Background TP53 mutations are frequently linked to an immunosuppressive tumor microenvironment and resistance to immune checkpoint blockade (ICB). However, their mechanistic role in shaping antitumor immunity in advanced prostate cancer remains unclear. Methods We generated CRISPR-Cas9-engineered murine prostate cancer models harboring the Trp53 p.R245Q knock-in mutation (orthologous to human TP53 p.R248Q). Tumor growth and response to anti-PD-1 therapy were evaluated in vivo. Single-cell RNA sequencing and integrated immune profiling were performed to characterize stromal and immune remodeling. Chromatin immunoprecipitation assays were used to assess mutant p53 binding and histone modifications at the Cxcl10 promoter. Statistical significance was assessed using Student’s t-test, Wilcoxon rank-sum test, and one-/two-way ANOVA, as appropriate. Results Mutant p53 accelerated tumor progression yet unexpectedly enhanced responsiveness to anti-PD-1 therapy within an otherwise suppressive microenvironment. Single-cell transcriptomics revealed epithelial lineage and metabolic rewiring, accompanied by depletion of cancer-associated fibroblasts and a shift toward immune-permissive stromal states. Immune profiling demonstrated increased infiltration of cytotoxic CD8⁺ granzyme B⁺ T cells and augmented lymphoid and vascular features. Mechanistically, mutant p53 occupied the Cxcl10 promoter, remodeled local chromatin by enriching H3K4me3 while reducing repressive histone marks, and transcriptionally upregulated Cxcl10. This established a CXCL10–CXCR3 chemotactic axis that promoted recruitment of cytotoxic CD8⁺ T cells and sensitized tumors to PD-1 blockade. Consistently, cohort analysis further supported that high CXCL10 expression correlated with immune activation and clinical benefit from ICB. Conclusions These findings indicate that mutant p53 can reprogram immune-cold prostate tumors into immune-hot ecosystems through coordinated epigenetic, metabolic, and stromal-immune remodeling. TP53 mutation status may therefore inform patient stratification and combinatorial immunotherapeutic strategies targeting the CXCL10–CXCR3 axis.

IntroductionPositron emission tomography/computed tomography (PET/CT) has demonstrated significant clinical utility in the localization of infectious foci, yet its application in nephrolithiasis-associated renal infections remains underexplored. MethodsThis retrospective cohort study assessed the diagnostic efficacy of 18F-FDG PET/CT in 120 lung cancer patients with radiologically confirmed nephrolithiasis across multiple centers. Quantitative analyses included calculation of diagnostic accuracy parameters, Pearson correlation between standardized uptake values (SUVmax), calculi burden, and serum cytokine profiles. Complementary experimental validation was performed using a murine calcium oxalate (CaOx) nephrocalcinosis model, utilizing micro-CT to analyze crystal deposition and inflammatory activity. ResultsClinically, PET/CT detected focal FDG uptake in 77 patients (64.2%), demonstrating 85.7% sensitivity and 76.7% specificity for infection identification. SUVmax positively correlated with stone burden and proinflammatory cytokines. The larger the size of the stone, the more severe the kidney infection, which in turn further aggravated the development of the stone. Furthermore, preclinical micro-PET/CT in CaOx mice revealed spatial concordance between crystal deposition and metabolic activity, paralleling human cytokine trends. DiscussionIn lung cancer patients with concomitant nephrolithiasis, 18F-FDG PET/CT demonstrates high diagnostic yield for detecting renal infection foci and may serve as a valuable tool for preoperative risk assessment. These findings provide a foundation for future studies in broader nephrolithiasis populations.

Our objective was to conduct a thorough evaluation of the burden of CKD and its associated anemia by age and sex at the global, regional, and national levels, with projections extending to 2050. The data from the Global Burden of Diseases (GBD) 2021 were used to describe relevant indicators of CKD and its associated anemia. At different geographic levels, subgroup analysis was carried out by sex, age, and Socio-Demographic Index (SDI). The time trend was examined using the joinpoint regression and decomposition analyses, and predictive analysis was utilized to further estimate the disease burden to 2050. The incidence, prevalence, mortality, and Disability-Adjusted Life Years (DALYs) of CKD, along with the prevalence and Years Lived with Disability (YLDs) of CKD-associated anemia, maintained a steady increase and would continue until 2050. In addition, the ASRs of mortality and DALYs attributable to CKD in 2021 were highest in low SDI regions. Regionally, CKD exhibited the greatest ASRs of mortality and DALYs in Central Latin America in 2021. Meanwhile, the disease burden of CKD and its associated anemia also showed significant differences at different national levels probably mainly due to population growth and aging. Moreover, the prediction analysis showed that the ASR of incidence attributable to CKD continued to increase. With the global population growth and aging, the disease burden of CKD and its associated anemia is still high and varies significantly at the global, regional, and national levels, which requires healthcare professionals to refine targeted interventions.

Prostate cancer is a heterogeneous malignancy with a complex tumor microenvironment (TME) composed of various cellular components, including fibroblasts. These fibroblasts, particularly cancer-associated fibroblasts (CAFs), are crucial in shaping the TME and influencing cancer progression. Catechol-O-methyltransferase (COMT), a key enzyme involved in the metabolism of catecholamines and oxidative stress regulation, has recently been implicated in cancer biology. This study aims to explore the molecular landscape of fibroblasts in prostate cancer and evaluate the prognostic significance of COMT expression in this context. We performed an integrated single-cell RNA sequencing (scRNA-seq) analysis on prostate cancer samples from Gene Expression Omnibus (GEO) databases. Fibroblast subpopulations were identified through clustering, and functional gene signatures for each subgroup were characterized. Prognostic analysis was carried out using univariate and multivariate Cox regression to identify genes associated with patient survival, culminating in a risk score model using data from the Cancer Genome Atlas (TCGA). Additionally, immunofluorescence assays were used to validate COMT expression in tumor-derived fibroblasts. Our single-cell sequencing analysis revealed three distinct fibroblast subpopulations, each with unique gene expression profiles linked to extracellular matrix remodeling, immune modulation, and cellular stress responses. COMT was identified as a key gene in tumor-derived fibroblasts, with its expression significantly higher in tumor samples compared to normal tissues. The risk score model, based on COMT and other fibroblast-associated genes (QSOX1, TAX1BP3, CCDC66, MTCH1, ARL2BP), successfully stratified patients into high-risk and low-risk groups, with higher risk scores correlating with poorer survival outcomes. Immunostaining confirmed the overexpression of COMT in tumor-derived fibroblasts, consistent with bioinformatics analysis. This study underscores the significant role of fibroblasts, particularly CAFs, in prostate cancer progression. Our findings highlight COMT as a critical regulator of the tumor microenvironment and a promising prognostic marker. The integration of single-cell RNA-seq with clinical data offers new insights into fibroblast heterogeneity and the potential for COMT as a therapeutic target in prostate cancer. Further research is needed to validate these findings and explore the mechanistic role of COMT in prostate cancer progression and therapeutic resistance.