Hainan 301 Hospital

Renal interstitial fibrosis (RIF) is the cardinal pathological hallmark of chronic kidney disease (CKD). Although the stem-cell factor (SCF)/c-kit axis has been implicated in kidney fibrogenesis, its cell-specific role and downstream mechanism in tubular epithelial cells (TECs) remain undefined. We investigated whether TEC-derived SCF/c-kit signaling propels RIF after unilateral ureteral obstruction (UUO) via Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) activation. Using the Cre-loxP system, a renal tubular epithelial cell-specific c-kit gene knockout mouse model (Ggt1-Cre c-kit−/−) was established. Renal interstitial fibrosis was induced in both C57BL/6J (WT) and Ggt1-Cre c-kit−/− mice via UUO surgery. The extent of fibrosis was evaluated by assessing renal function indicators (serum creatinine and blood urea nitrogen), renal histopathology (PAS and Sirius red staining), and the expression of fibrosis markers (α-SMA, Vimentin, and Collagen I). Western blot and immunofluorescence techniques were employed to detect the expression of fibrosis markers, key proteins of the NF-κB pathway (p-p65, p65, p-IκBα, and IκBα), and inflammatory cytokines (Interleukin (IL)-6 and IL-1β). Primary renal tubular epithelial cells were isolated and cultured ex vivo, and treated with SCF and the NF-κB-specific inhibitor SC-75741 to evaluate the degree of cellular fibrosis and the activation status of the NF-κB pathway. Fourteen days after UUO, renal SCF and c-kit expression paralleled the rise in fibrotic markers. TEC‑specific deletion of c‑kit ameliorates the initial decline in renal function, attenuates tubular injury, reduces collagen deposition, and downregulates the expression of fibrotic proteins. Genetic deletion of c-kit significantly inhibits NF-κB phosphorylation and the expression of inflammatory cytokines IL-6 and IL-1β. In vitro, SCF provoked a fibrogenic phenotype in WT TECs that was abolished by either c-kit deletion or SC-75741. The SCF/c-kit signaling pathway in TECs promotes renal interstitial fibrosis in UUO mice via activation of the NF-κB pathway. Targeted inhibition of c-kit in TECs alleviates inflammatory responses and fibrosis, improves renal function, and may offer a novel therapeutic target for delaying the progression of CKD.

Double J (DJ) stent encrustation is a common postoperative complication that can lead to severe infection, obstruction, or stent retention. Existing predictive models primarily focus on indwelling time and urinary pH but have largely excluded patients with chronic kidney disease (CKD), limiting their applicability. This multicenter study aimed to develop and externally validate a nomogram for individualized prediction of DJ stent encrustation, incorporating renal function status for the first time. A total of 760 patients who underwent upper urinary tract stone surgery with postoperative DJ stent placement were retrospectively analyzed. Clinical, biochemical, and behavioral variables were evaluated. Multivariate logistic regression identified independent predictors, which were used to construct a predictive nomogram. External validation was performed using an independent cohort of 337 patients from another tertiary hospital. Model discrimination, calibration, and clinical benefit were assessed by receiver operating characteristic (ROC) curve analysis, bootstrap calibration, and decision curve analysis (DCA). Stent encrustation occurred in 121 patients (15.9%). Four variables-stent indwelling time, urine pH, daily water intake, and renal function stage-were independently associated with encrustation (p < 0.05 for all). The nomogram achieved excellent discrimination (AUC = 0.877) and maintained strong external performance (AUC = 0.884). CKD significantly increased risk in a dose-dependent manner, and interaction analysis revealed a synergistic effect between CKD and urine pH (p = 0.002), explaining the lack of independent significance of pH in CKD subgroups. This study established and externally validated the first nomogram for predicting DJ stent encrustation that includes CKD as a systemic variable. The model demonstrates high accuracy and generalizability, offering a practical tool for early identification of high-risk patients, particularly those with renal impairment, to guide individualized stent management and prevent irreversible renal damage.

To investigate the significance of DCUN1D5 in colorectal cancer (CRC) progression and determine the underlying mechanism. We analyzed DCUN1D5 expression levels in CRC tissues using the TCGA and GEO databases and conducted immunohistochemistry and qPCR in retrieved CRC tissues. shRNA-mediated knockdown of DCUN1D5 in CRC cell lines was performed to investigate its effects on cell growth and motility. In addition, DCUN1D5-mediated promotion of CUL1 neddylation was examined using immunoblotting, the antitumor effects of inhibiting the neddylation pathway was evaluated using the inhibitor MLN4924, and the effects of silencing DCUN1D5 and MLN4924 treatment were validated in vivo using xenograft models. DCUN1D5 was found to be significantly overexpressed in CRC tissues, and its knockdown impaired CRC cell proliferation and migration, which was associated with reduced CUL1 neddylation. Inhibition of the neddylation pathway using the NEDD8 inhibitor MLN4924 supported these observations. In vivo, DCUN1D5 silencing and MLN4924 treatment led to reduced tumor growth and metastasis. DCUN1D5 contributes to the growth and motility of CRC in vitro and in vivo.

<title>Abstract</title> Menopausal hormone therapy (MHT) alleviates climacteric symptoms, but still, microbiome-wide effects and efficacy determinants remain uncharacterized. In this six-month longitudinal study of 356 perimenopausal women receiving oral MHT, we integrated serial clinical assessments with multi-site metagenomic profiling. MHT elicited multi-system estrogenic responses, including neuroendocrine restoration, symptom alleviation, metabolic shifts, and uterine changes. MHT induced site-specific microbiome remodeling, most prominently in vaginal and urinary niches, with moderate oral and minimal gut changes. Generally, MHT reduced Gardnerella vaginalis and increased Lactobacillus crispatus levels in vagina. Baseline vaginal L. crispatus abundance strongly predicted subsequent urogenital restoration. Additionally, baseline urogenital community states stratified therapeutic trajectories: vaginal G. vaginalis-dominated individuals showed transitions toward eubiosis, whereas diversified communities improved less. MHT efficacy corresponded to serum estrogen elevation, linked to baseline gut community type. Individuals with a Phocaeicola vulgatus-driven community type exhibited greater hormonal responsiveness and superior outcomes than those dominated by Prevotella copri. These findings support a precision MHT framework integrating gut community and urogenital typing to guide stratification and targeted interventions.

Percutaneous nephrolithotomy (PCNL) is the standard treatment for large or complex renal calculi; however, postoperative hemorrhage requiring selective renal arterial embolization (SRAE) remains a rare but serious complication. Chronic kidney disease (CKD) may further increase bleeding risk, but predictive models for SRAE in this population are lacking. To develop and validate a nomogram for predicting the need for SRAE in patients with CKD who experience hemorrhage after PCNL. This retrospective cohort study included 3153 patients who underwent PCNL in two tertiary hospitals between June 2010 and June 2025. Of these, 986 had CKD. A total of 331 patients with post-PCNL hemorrhage and CKD were analyzed, including 299 who received conservative management and 32 who underwent SRAE. Clinical variables were compared between groups, and independent risk factors were identified using multivariate logistic regression. A nomogram was developed from the significant predictors and validated using receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). Among 331 patients with post-PCNL hemorrhage and CKD, 32 (9.7%) required SRAE. Compared with the conservative group, SRAE patients had a higher rate of prior ipsilateral kidney intervention (31.3% vs. 11.4%), more acute hemorrhage (40.6% vs. 14.4%), and greater hemoglobin drop (39.5 ± 10.7g/L vs. 25.3 ± 8.8g/L), and a notably higher proportion of the absence of hydronephrosis (all p < 0.05). Multivariate analysis identified hydronephrosis grade, past ipsilateral intervention, hemorrhage type, and hemoglobin drop as independent predictors of SRAE (p < 0.05). The nomogram incorporating these variables achieved excellent discrimination (AUC = 0.901, C-index = 0.897) and good calibration (Hosmer-Lemeshow, χ² = 6.357, p = 0.607), with robust performance in the external validation cohort (AUC = 0.893). Decision curve analysis demonstrated favorable clinical utility. Among all 3,153 PCNL cases, patients with CKD had a significantly higher incidence of hemorrhage (33.6% vs. 19.3%, p < 0.001), while the SRAE rate was comparable to those with normal renal function (3.2% vs. 2.8%, p = 0.508). The nomogram developed in this study provides a reliable and individualized tool for predicting the need for embolization among CKD patients who have already developed post-PCNL hemorrhage. Incorporating variables such as hemoglobin drop, hemorrhage type, hydronephrosis grade, and prior ipsilateral intervention, this model can assist clinicians in early risk stratification and optimize decision-making for timely intervention.