BACKGROUND:This study aimed to estimate the trends in the prevalence of kidney stones among adults with diabetes in the United States from 2007 to 2020 and to examine sex- and race/ethnicity-specific differences. METHODS:This study analyzed 31,116 adult participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2020. Survey-weighted multivariable logistic regression was used to examine the association between diabetes and kidney stones, and survey-weighted linear regression was used to evaluate temporal trends overall and across subgroups defined by sex and race/ethnicity. RESULTS:Diabetes was associated with higher odds of kidney stones (OR = 1.63, p < 0.001). Between 2007 and 2020, the prevalence of both diabetes and kidney stones increased significantly among US adults (both p for trend <0.05). In subgroup analyses by sex and race, diabetes prevalence increased significantly over time among men and non-Hispanic Whites (both P for trend <0.05). Among adults with diabetes, kidney stone prevalence increased from 14.3% to 16.1% (p for trend = 0.446). Among men with diabetes, kidney stone prevalence changed from 16.6% to 20.2% (p for trend = 0.527), whereas among women with diabetes, it changed from 11.8% to 12.8% (p for trend = 0.848). By race/ethnicity, among diabetic Hispanics, kidney stone prevalence significantly increased from 8.7% to 14.8% (p for trend = 0.017). Non-Hispanic White adults with diabetes had the highest kidney stone prevalence (17.4% to 21.7%, p for trend = 0.468), and non-Hispanic Black adults with diabetes changed from 7.7% to 6.9% (p for trend = 0.775). CONCLUSION:From 2007 to 2020, the diabetes prevalence significantly increased. Kidney stone prevalence increased significantly among Hispanic adults with diabetes and remained high among men with diabetes and non-Hispanic White adults with diabetes. These subgroups may warrant targeted prevention and clinical attention.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory condition with limited treatments. Although macrophages are implicated in its pathogenesis, the mechanisms driving their phenotypic switching remain unclear. This study identifies CCR1's role in IC/BPS and evaluates CCR1 inhibition as a therapeutic strategy. Integrated bulk and single-cell RNA sequencing reveal enrichment of pro-inflammatory CCR1⁺ macrophages in bladder tissue from patients with IC/BPS. In a lipopolysaccharide-induced rat model, pharmacological inhibition of CCR1 suppresses M1 polarization, promotes M2 polarization, and improves pain thresholds, urinary symptoms as well as bladder inflammation. Mechanistically, CCR1 knockdown enhances FOXO1 phosphorylation and degradation, reduces its nuclear translocation, and activates PPARγ signaling to promote M2 polarization. Analysis of clinical samples shows increased CCL7 levels in bladder tissue and urine, with urinary levels correlating with symptom severity. These findings identify CCR1 as a candidate target for further therapeutic evaluation in IC/BPS.

The COVID-19 pandemic has significantly impacted disease burdens, yet updated nocturia epidemiological data remain limited. This study characterized age-sex-race disparities in nocturia prevalence and evaluated pandemic-related temporal changes. Using NHANES data (2017–2023), this cross-sectional study included 10,946 adults (≥ 20 years). Primary outcomes were nocturia prevalence (≥ 1 and ≥ 2 nightly episodes). Analyses incorporated sampling weights and multivariable logistic regression. Overall weighted prevalence reached 71.9

Bladder discomfort, urgency, and frequency of urination are the hallmarks of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic illness. Although the precise etiology remains unclear, numerous clinical investigations have established inflammation as a pivotal factor in its pathogenesis, encompassing uroepithelial damage, mast cell activation, and neuroinflammatory responses. This review delineates the pathological features and classification of IC/BPS, emphasizing the contribution of inflammatory mechanisms and the involvement of cytokines as key mediators in disease progression. The insights presented aim to guide the advancement of innovative treatment approaches.

Stress urinary incontinence (SUI) seriously affects patients’ daily lives. Early identification of risk factors for SUI has positive social and clinical significance. This study aimed to develop and externally validate predictive models for female SUI using clinical data and pelvic floor ultrasound (PFU) parameters through multivariate logistic regression (MLR) and the C5.0 decision tree (DTC5.0). The training cohort comprised basic data and PFU parameters from 291 patients across two hospitals. Risk factors for SUI were identified through differential analysis and incorporated into MLR and DTC5.0 models to predict SUI risk. An external validation cohort of 115 patients was obtained via telephone follow-up. Model performance was evaluated and compared in terms of the AUC, accuracy, specificity, sensitivity, Youden index, positive predictive value (PPV), and negative predictive value (NPV). Both models identified five key predictors: vaginal delivery, hysterectomy, bladder neck mobility, urethral funnel formation, and perineal body hypermobility. In the training cohort, the MLR model achieved an AUC of 0.873 (95

BACKGROUND:Kidney stones are a significant health concern in the United States, and their increasing prevalence is linked to increasing obesity rates. This study aimed to assess the trends in kidney stone prevalence among U.S. adults with obesity from 2007 to 2020 using National Health and Nutrition Examination Survey (NHANES) data. MATERIALS AND METHODS:This cross-sectional analysis used anonymized NHANES data from six cycles (2007-2020). Prevalences were estimated using NHANES sample weights; age-standardized prevalences were determined using 2020 census data. Survey-weighted multivariate logistic regression and linear regression models were used to assess risk factors and trends, respectively. Subgroup analyses were performed according to sex, race/ethnicity, and poverty-income ratio (PIR). RESULTS:The overall age-standardized prevalence of kidney stones increased from 9.4% (2007-2008) to 10.2% (2017-2020). The prevalence among individuals with obesity significantly increased from 11.0% to 12.5% ( P for trend = 0.035). The prevalence of kidney stones in females with obesity significantly increased from 8.8% to 11.5% ( P for trend = 0.042), whereas males with obesity showed a slight increase (13.4% to 14.0%). Racial/ethnic disparities were evident among those with obesity: non-Hispanic Whites showed a modest increase (12.4% to 14.2%), Hispanics exhibited a notable increase (7.5% to 10.9%; P for trend = 0.017), and non-Hispanic Blacks had a stable prevalence that increased slightly (5.9% to 6.8%; P for trend = 0.304). The prevalence increased (10.2% to 12.9%; P for trend = 0.051) among individuals with obesity and high PIRs and decreased (12.8% to 11.4%) among those with low PIRs. CONCLUSIONS:This study highlights an upward trend in the prevalence of kidney stones among U.S. adults with obesity, from 2007 to 2020. Our findings emphasize the need for targeted public health strategies to address this issue, especially among populations at higher risk due to obesity and socioeconomic factors.

Background:U2AF homology motif kinase 1 (UHMK1) has been associated with RNA processing and protein phosphorylation, thereby influencing tumor progression. The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer (PCa). Methods:In this study, we systematically evaluated the expression and prognostic significance of UHMK1 in public databases, followed by validation through immunohistochemistry (IHC) in PCa specimens. Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo. Additionally, a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity. Results:Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis, as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining. Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis, while its overexpression promoted these processes. Mechanistically, we identified that UHMK1 phosphorylates nuclear receptor coactivator 3 (NCOA3), which subsequently activates activating transcription factor 4 (ATF4) to upregulate methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) transcription. Interestingly, MTHFD2 was found to reciprocally enhance UHMK1 expression, establishing a positive feedback loop. Conclusions:In conclusion, our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression. Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.

Background: Increasing evidence shows that lipid metabolism is closely related to the pathogenesis of stress urinary incontinence (SUI). This study aimed to investigate the association between high-density lipoprotein cholesterol (HDL-C) levels and female SUI, evaluate dose-response relationships, and determine the causal effect of HDL-C on SUI risk. Materials and methods: Utilizing cross-sectional data from the National Health and Nutrition Examination Survey (2001-2020, n = 18,415), we assessed the dose-response relationship between HDL-C and SUI using restricted cubic splines and weighted logistic regression. Mendelian randomization (MR) analyses leveraged genetic instruments from European cohorts (HDL-C: n = 9,796; SUI: 5,926 cases/211,672 controls) to infer causality. Subgroup analyses emphasized interactions between HDL-C and BMI. Results: A 1 mg/dL increase in HDL-C was linearly associated with a 0.5% reduction in SUI risk (OR = 0.995, 95% CI: 0.986-0.991, P < 0.001). Participants in the highest HDL-C quartile (Q4) exhibited a 25.1% lower SUI risk compared to Q1 (OR = 0.749, 95% CI: 0.652-0.859). Notably, the protective effect of HDL-C was markedly stronger in overweight/obese individuals (BMI ≥ 25 kg/m²: OR = 0.992, P = 0.006; BMI ≥ 30 kg/m²: OR = 0.991, P = 0.001), with significant interaction (P for interaction = 0.015). MR analyses confirmed a causal protective effect of HDL-C on SUI (IVW OR = 0.842, 95% CI: 0.744-0.953), and sensitivity analyses supported robustness. Conclusions: Elevated HDL-C levels are causally linked to reduced SUI risk, with amplified protection in overweight/obese populations. These findings highlight the importance of maintaining healthy HDL-C levels as a targeted strategy for SUI prevention, especially in high-BMI individuals.

Natural killer (NK) cells are capable of directly targeting and eliminating cancer cells without prior exposure to specific antigens. Adoptive NK cell therapy is increasingly recognized as a promising strategy within the realm of cancer immunotherapy. However, the clinical efficacy of NK cells is often curtailed by various suppressive factors within the tumor microenvironment (TME). Recent advancements in biomaterials have offered innovative solutions to these challenges by facilitating the engineering and modification of NK cells. This review presents the latest developments in engineering modifications and advancements in NK cell-based therapies. We outline the underlying anti-cancer mechanisms and clinical applications of engineered NK cells, summarizing common modification strategies and their respective mechanisms. Additionally, we highlight the advantages conferred by NK cell engineering. Finally, we address the current challenges and explore future perspectives in the engineering of NK cells to advance their efficacy in cancer immunotherapy.

Interstitial cystitis (IC) is a chronic inflammatory bladder disorder lacking timely diagnostic and therapeutic options. Here, we propose a unitary theranostic nanocluster-antibody-drug conjugate (NADC) by covalently attaching dihydroorotate dehydrogenase inhibitors (DHODHi) and ultrasmall gold quantum clusters (AuQCs) to a nerve growth factor (NGF) antagonistic antibody, with multimodality imaging contrasts. Combining anti-inflammatory effects from all individual components, intravesical NADC specifically homed to mucosal lesions with tissue-residing NGF overexpression in the voided bladder, where it neutralized and formed immunocomplexes with secreted NGF to be intracellularly internalized by inflammatory macrophages for payload release through the FcγR-mediated pathway. NADC alleviated inflammation in chronic, acute, and prophylactic IC models of rats, as revealed by behavioral and pathological evaluations. Transcriptomics unveiled cytokine modulation and concomitant inhibition of perturbed IL-17, NF-κB, TNF, and JAK-STAT signaling pathways. Notably, NADC indirectly remodeled the host bladder microbiota by differentially varying anti-inflammatory and pro-inflammatory bacterial diversities. Distinct from conventional nanoparticles conjugated with antibodies or drugs, NADC relies on the antibody framework, outperforms clinical standard-of-care agents, and represents emerging precision medicine with translational potential for IC theranostics in clinical practice.

OBJECTIVE To explore the relationship between serum estrogen levels and urinary incontinence in a nationally representative female population. MATERIALS AND METHODS We included women who had serum estradiol measurements and self-reported urinary incontinence problems in the 2013-2016 National Health and Nutrition Examination Survey cycles. A weighted multivariable logistic regression model was used to determine the association between urinary incontinence and serum estrogen levels after adjusting for age, race, Body Mass Index, diabetes, venipuncture, hypertension, poverty-to-income ratio, smoking, marital status, alcohol use, education, and menopause. RESULT A total of 4114 individuals were ultimately included in our study. Of these women, 1200 (29.17%) complained of urge urinary incontinence (UUI), 1674 (40.69%) complained of stress urinary incontinence (SUI), 730 (17.74%) complained of mixed urinary incontinence (MUI). Women in the lowest quartile of serum estrogen were more likely to complain of UUI compared to those in the highest quartile (OR = 1.885; 95% CI = 1.042-3.412, P = .039). No association was noted between serum estrogen levels and SUI or MUI. CONCLUSION Our study shows a significant association between low serum estrogen level and the increased likelihood of UUI in women. Further research is required to validate our findings, elucidate the physiological mechanisms that underlie them, and assess potential therapeutic implications. UROLOGY 188: 63-69, 2024. (c) 2024 Elsevier Inc. All rights reserved.

This study aims to investigate the anti-inflammatory effects of Resveratrol (RES) in the treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) by integrating network pharmacology, molecular docking, and experimental validation. Potential targets of RES were identified using DrugBank and SwissTargetPrediction, while IC/BPS-related targets were obtained from DisGeNET and Genecards. Molecular docking was performed using UCSF Chimera and SwissDock to validate the binding affinity of RES to key targets. Experimental validation involved treating TNF-α induced urothelial cells with RES, followed by assessments using RT-qPCR, ELISA, and Western blotting. A total of 86 drug targets and 211 disease targets were analyzed, leading to the identification of 8 key therapeutic targets for RES in IC/BPS treatment. Molecular docking revealed a strong affinity of RES for ESR2, with notable interactions also observed with SHBG, PTGS2, PPARG, KIT, PI3KCA, and AKT1. In vitro experiments confirmed that RES significantly alleviated the inflammatory response in TNF-α-induced urothelial cells, normalizing the expression levels of ESR2, SHBG, PPARG, and AKT1. RES can modulate critical pathways involving ESR2, SHBG, PPARG, and AKT1, highlighting its potential as a therapeutic agent for IC/BPS. This study provides a theoretical foundation for the clinical application of RES in treating IC/BPS.

Androgen receptors are expressed in the pelvic floor and lower urinary tract. However, the association between serum testosterone and overactive bladder (OAB) in women remains unclear. This study aimed to investigate their association in a nationally representative population. In this cross-sectional study, we collected data on female participants older than 20 years with serum total testosterone measurements and OAB questionnaires from the 2011–2016 National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression models were used to analyze the relationship between testosterone and OAB in women. Data on 4991 women was analyzed in this study, of whom 25.9

Background Inflammation plays a key role in the pathogenesis of stress urinary incontinence (SUI). The present study investigated the association between the systemic immune-inflammation index (SII) and SUI in a nationally representative adult population. Methods Data from the 2007-2016 National Health and Nutrition Examination Survey were analyzed. SUI was determined by self-report of urine leakage caused by activity such as coughing, lifting, or exercise. The SII was calculated as (platelet count × neutrophil count)/lymphocyte count. Survey-weighted logistic regression models were used to analyze the relationship between the SII and SUI. Results Data from 18,797 participants, of whom 2695 (14.3%) reported SUI, were included. After adjusting for covariates, multivariate logistic models revealed that a high SII was associated with an increased overall likelihood of SUI (odds ratio [OR] 1.116 [95% confidence interval (CI) 1.018–1.223]; P = 0.0206). A higher risk was observed for monthly and weekly SUI (OR 1.144 [95% CI 1.009–1.297]; P = 0.0359, and OR 1.205 [95% CI 1.002–1.449]; P = 0.0478, respectively). Separate interaction analyses revealed no significant effects of age, gender, race, body mass index, marital status, alcohol use, or vigorous recreational activities on the association between the SII and SUI. Conclusions Results revealed that a high SII associated with an increased risk for SUI. The SII may serve as a novel predictive biomarker in clinical practice to predict the occurrence and progression of SUI symptoms. A physiological mechanism underlying this relationship could be proposed and further evaluated in translational and basic scientific studies.

Interstitial cystitis (IC) is a chronic inflammatory disorder characterized by recurring severe pain in the bladder and surrounding pelvic areas, lacking timely diagnostic and therapeutic options. Here, we propose a unitary theranostic nanocluster-antibody-drug conjugate (NADC) by covalently placing dihydroorotate dehydrogenase inhibitors (DHODHi) and ultrasmall gold quantum clusters (AuQCs) on a nerve growth factor (NGF) antagonistic antibody with simultaneous X-ray computed tomographic and near-infrared fluorescence imaging contrasts. Combining anti-inflammatory effects from all individual components, intravesical NADC specifically homed to bladder mucosal lesions and capably alleviated inflammation in chronic, acute, and prophylactic IC models of rats, as revealed by behavioral and pathological evaluations. Transcriptomics unveiled cytokine modulation and concomitant inhibition of perturbed IL-17, NF-κB, TNF, and JAK-STAT signaling pathways. Interestingly, the NADC reconstructed the host bladder microbiota by differentially varying anti-inflammatory and pro-inflammatory bacteria diversities. Distinct from conventional nanoparticles conjugated with antibodies and drugs, NADC relies on the antibody framework and represents a state-of-the-art category of precision theranostic agents with translational potential for diagnosing and treating IC patients.### Competing Interest StatementThe authors have declared no competing interest.