Background Recurrence after curative-intent resection remains common in hepatocellular carcinoma (HCC), and whether postoperative incretin-based treatment choice influences outcomes in patients with type 2 diabetes (T2D) is unclear. Objective To determine whether postoperative initiation of glucagon-like peptide-1 receptor agonists (GLP-1RAs), compared with dipeptidyl peptidase-4 inhibitors (DPP-4is), is associated with improved recurrence-free and overall survival after curative-intent resection for HCC. Design Active-comparator, new-user target trial emulation using electronic medical records from 36 hospitals across China from 2014 to 2023, with follow-up through 1 October 2025. Eligible adults had histologically confirmed HCC and T2D, underwent R0 resection and initiated a GLP-1RA or DPP-4i within postoperative days 0 to 90. Time zero was the first qualifying prescription or order date. The primary estimand was intention-to-treat; a prespecified per-protocol analysis assessed sustained adherence. The primary outcome was recurrence-free survival (RFS), treating death without recurrence as a competing event; overall survival (OS) was secondary. The study was registered with the Chinese Clinical Trial Registry (ChiCTR2600118495). Results Among 42 855 patients with HCC and T2D who underwent liver resection, 1249 were included in the final analytical cohort, including 723 DPP-4i initiators and 526 GLP-1RA initiators; median follow-up was 50.8 months. In weighted intention-to-treat analyses, GLP-1RA versus DPP-4i initiation was associated with longer RFS (cause-specific HR 0.80, 95% CI 0.67 to 0.96; p=0.016) and OS (HR 0.58, 95% CI 0.47 to 0.71; p<0.001). Per-protocol analyses were directionally consistent. Conclusion Postoperative GLP-1RA initiation, compared with DPP-4i initiation, was associated with delayed recurrence and longer OS; prospective confirmation is warranted. Trial registration number ChiCTR2600118495.

Cholangiocarcinoma (CCA) is a highly aggressive malignancy of the biliary epithelium, with its incidence and mortality rates continuing to rise worldwide. Advances in high-throughput sequencing and metabolomic technologies have intensified interest in elucidating the role of the microbiome in CCA. Microbial dysbiosis may contribute to tumor initiation and progression by inducing chronic inflammation, altering metabolic pathways, and modulating the immune microenvironment. Moreover, these microbial alterations have been associated with therapeutic resistance, underscoring their potential impact on disease progression and treatment outcomes. This review summarizes the potential origins of intratumoral microorganisms and the microbiome alterations associated with distinct CCA subtypes. Crucially, we critically evaluate the methodological challenges inherent to low-biomass biliary samples—including contamination risks and confounding factors such as cholestasis and medical interventions—and distinguish between associative and causal evidence in current literature. Collectively, this work aims to provide a rigorous theoretical framework and novel insights for microbiome-based strategies in the early diagnosis and treatment of CCA.

Background: Recurrence after curative-intent resection remains a major challenge in hepatocellular carcinoma (HCC), but current prognostic models rarely connect preoperative imaging phenotype with postoperative histomorphology. We developed a clinically separated, cross-scale multimodal survival framework integrating contrast-enhanced ultrasound (CEUS), whole-slide pathology images, and clinical variables for recurrence-free survival (RFS) risk stratification after HCC resection. Methods: In this retrospective two-center study, 384 patients with pathologically confirmed HCC were included. The Shandong Provincial Qianfoshan Hospital cohort was used for model development, including training and internal validation, and the Qilu Hospital of Shandong University cohort was held out as an external test cohort. We evaluated a preoperative CEUS plus clinical model, a postoperative WSI plus clinicopathologic model, and a full CEUS plus WSI plus clinical benchmark. The primary endpoint was RFS, with early recurrence within 24 months assessed as a clinically relevant horizon. Findings: In the external test cohort, the full multimodal benchmark achieved a C-index of 0.823 (95% CI 0.761--0.885), with 1-year and 2-year time-dependent AUCs of 0.882 and 0.861, respectively. The model showed calibrated risk estimation, favourable decision-curve performance, and clear RFS stratification.I nterpretation: Cross-scale integration of CEUS, WSI, and clinical information may improve postoperative recurrence risk stratification and provide a biologically coherent link between perfusion phenotype and histomorphologic recurrence patterns. Prospective multicentre validation is warranted before clinical implementation.

Ureteral stricture is a significant complication after ureteroscopic lithotripsy (URSL). This study aimed to identify risk factors for post-URSL ureteral stricture and develop a nomogram to predict the timing and probability of stricture occurrence within 1–3 years postoperatively, thereby facilitating individualized follow-up. We enrolled patients who underwent holmium laser ureteroscopic lithotripsy (URSL) at a single institution between January 1, 2014, and December 31, 2021, and were diagnosed with postoperative ureteral stricture. Baseline characteristics, in-hospital data, surgical indicators, computed tomography data, and laboratory test results of patients with and without stenosis were compared. Cases (n = 70) were patients diagnosed with postoperative ureteral stricture; controls (n = 70) were selected using propensity score matching (age, sex, stone laterality, surgery date) from patients without stricture. T-tests, Pearson’s chi-squared, or Fisher’s exact tests, LASSO and Cox regression analyses, receiver operating characteristic and Kaplan–Meier curve analyses, and nomogram analysis were used to predict post-URSL ureteral stricture risk factors and timing. Hypertension incidence (P = 0.038), ureteral stent placement time (P = 0.002), stone location (P = 0.04), and hydronephrosis grade (P < 0.001) differed significantly between the groups, and stone impaction were independent risk factors for ureteral stricture. The nomogram showed good discrimination (C-index 0.720) and calibration. Preoperative fever appeared as a protective factor but should be interpreted cautiously due to potential confounding. The nomogram, which based on hydronephrosis grade, ureteral stone location, and incarcerated stones can predict post-URSL ureteral stricture risk and may guide personalized follow-up. External validation is needed before clinical application.

G protein-coupled receptors (GPCRs) mediate most cellular responses to hormones, neurotransmitters, and environmental stimulants. However, whether GPCRs participate in tissue homeostasis through ferroptosis remains unclear. Here we identify that GPR56/ADGRG1 renders cells resistant to ferroptosis and deficiency of GPR56 exacerbates ferroptosis-mediated liver injury induced by doxorubicin (DOX) or ischemia-reperfusion (IR). Mechanistically, GPR56 decreases the abundance of phospholipids containing free polyunsaturated fatty acids (PUFAs) by promoting endocytosis-lysosomal degradation of CD36. By screening a panel of steroid hormones, we identified that 17α-hydroxypregnenolone (17-OH PREG) acts as an agonist of GPR56 to antagonize ferroptosis and efficiently attenuates liver injury before or after insult. Moreover, disease-associated GPR56 mutants were unresponsive to 17-OH PREG activation and insufficient to defend against ferroptosis. Together, our findings uncover that 17-OH PREG-GPR56 axis-mediated signal transduction works as a new anti-ferroptotic pathway to maintain liver homeostasis, providing novel insights into the potential therapy for liver injury.

ABSTRACT Obesity predisposes individuals to hypercoagulation, a key factor in life‐threatening complications like stroke and cardiovascular disease. While clotting factors are primarily secreted by the liver, the mechanisms linking obesity to hypercoagulation remain unclear. In this study, we established an obesity cohort and conducted genetic analyses, single‐nucleus and bulk RNA sequencing of human liver tissues, and in vitro experiments to elucidate the underlying mechanisms. Genetic analysis identified a causal relationship between body mass index (BMI) and coagulation parameters, specifically elevated fibrinogen levels. Clinical cohort data demonstrated a significant association between BMI and plasma fibrinogen levels and fibrinogen function. Hepatic transcriptomic data revealed a significant link between BMI and hepatic fibrinogen expression. snRNA‐seq data and deconvolution analysis of bulk RNA‐seq uncovered a specific hepatocyte subpopulation (Hep5) that was significantly increased and responsible for aberrant coagulation factor secretion in obesity. Pseudotime trajectory analysis indicated that increased interleukin 6 (IL6) signaling in obese patients contributed to the activation of the hepatocyte identity‐related transcription factor CEBPB, promoting the differentiation of other hepatocyte subpopulations into Hep5. Further analysis in an independent obesity cohort confirmed serum IL6 as a critical mediator of the BMI‐fibrinogen relationship, supporting the potential value of IL6 antibodies, which are currently in Phase 2b trials, for improving coagulation abnormalities. In vitro experiments demonstrated that the CEBPB inhibitor helenalin acetate reversed the aberrant expression of hepatocyte differentiation‐related genes induced by IL6. This study defines the hepatic transcriptomic landscape in obesity, elucidates mechanisms of fibrinogen elevation, and highlights therapeutic targets for managing hypercoagulation in obesity.

Oxylipins are important metabolic messengers for normal life activities, and olfactory receptors (ORs) are known for their low affinity for odor and are not considered oxylipin receptors. By developing the "anonymous receptor identification by reverse-G-protein pull-down" (ARIG) method, we identify orphan OR Or5v1/Olfr110 as an oxylipin 12(S)-hydroxyeicosapentaenoic acid (12(S)-HEPE) receptor. The serum from obese patients with increased BMI showed lower Or5v1/Olfr110-Gs activation compared with normal people. Systemic Or5v1/Olfr110 deficiency or liver-specific Or5v1/Olfr110 deficiency impaired glucose homeostasis, even after stimulation with 12(S)-HEPE. Engagement of 12(S)-HEPE with Olfr110 activated Gs-PKA-pATF2-Cpt1α signaling to reduce obesity through promotion of fatty acid oxidation in liver. Structural aided development of synthetic agonist HOR1-C59 improved glucose homeostasis, which is dependent on Or5v1/Olfr110 expression. Overall, we revealed that a high-affinity oxylipin-sensing OR plays key roles in metabolism. The beneficial effects of HOR1-C59 underscore the therapeutic value of small synthetic compounds that target ORs for disease treatment.

Objectives: Bladder cancer (BCa) progression is closely linked to the immune microenvironment. However, the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood. This study aims to identify a key molecule and elucidate its mechanisms, providing a theoretical basis for identifying novel therapeutic targets. Methods: Immune microenvironment-related genes in BCa were identified using The Cancer Genome Atlas and Shanghai Tenth People's Hospital datasets. Proteasome 26S subunit non-ATPase 2 (PSMD2) expression was validated via quantitative polymerase chain reaction (qPCR), Western blot (WB) analysis, and immunofluorescence (IF). In vitro and in vivo experiments confirmed the role of PSMD2 in cell proliferation, invasion, and migration. Kyoto encyclopedia of genes and genomes (KEGG) and Gene Ontology (GO) analyses were conducted to assess PSMD2's influence on immune microenvironment remodeling. A pathomics model predicted PSMD2 expression in patients with BCa. Results: PSMD2 was identified as a critical factor in BCa, with high expression correlating with poor prognosis and tumor progression. Mechanistically, PSMD2 enhances malignancy by promoting mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) phosphorylation within the mitogen-activated protein kinase (MAPK) signaling pathway. Combined bioinformatics and experimental analyses reveal that PSMD2 downregulates chemokine (C-X-C motif) ligand 14 (CXCL14) expression and secretion via the MAPK pathway, thereby remodeling the immune microenvironment and driving tumor progression. Pathomics analysis further supports the potential of PSMD2 expression as a predictive marker in BCa tissues. Conclusion: PSMD2 is overexpressed in BCa and significantly correlates with poor prognosis and tumor progression. It promotes malignant development and immune microenvironment remodeling through the MAPK pathway. Pathological analysis can predict PSMD2 expression, offering valuable insights into immunotherapy responses and survival outcomes.

The epidemiological shift toward non-B non-C hepatocellular carcinoma (NBNC-HCC) highlights the need for identifying prognostic markers in this population. While microvascular invasion (MVI) has been established in hepatitis virus-related HCC (HV-HCC), its role in NBNC-HCC remains unclear. This multicenter retrospective study analyzed 3308 patients with HCC undergoing curative resection (2012–2023). Risk factors for MVI were identified using logistic regression in the overall cohort. From this cohort, 439 patients with NBNC-HCC were stratified based on the MVI status and balanced using propensity score matching (PSM). Cox regression models and Kaplan–Meier analysis with log-rank test were employed to compare recurrence-free survival (RFS) and overall survival (OS) between MVI-positive and MVI-negative subgroups. The incidence of MVI was lower in the NBNC-HCC group compared to the HV-HCC group (31.44

Background: Combination therapies can convert unresectable hepatocellular carcinoma (uHCC) to resectable disease, but quantifying the unbiased survival benefit attributable to conversion remains methodologically challenging. This study aimed to rigorously evaluate the prognostic association of successful conversion and compare subsequent management pathways. Methods: In this retrospective study of 362 patients with uHCC treated with lenvatinib, programmed cell death 1 (PD-1) inhibitors, and transarterial embolization (TAE)-hepatic arterial infusion chemotherapy (HAIC), we quantified the survival association of conversion using a time-dependent Cox model to address immortal time bias. Treatment pathways were categorized as surgically managed conversion (SMC), medically maintained conversion (MMC), or conversion not-achieved. We employed inverse probability of treatment weighting (IPTW) and restricted mean survival time (RMST) analysis for robust comparisons. Results: The conversion rate was 34.0% (123/362). After adjustment, successful conversion was independently associated with significantly improved overall survival [OS; hazard ratio (HR) =0.39, 95% confidence interval (CI): 0.25-0.60, P<0.001]. A distinct clinical trajectory was observed: SMC patients had the most favorable prognosis (median OS not reached), followed by MMC (median OS not reached), with conversion not-achieved patients having the poorest survival (median OS 18.4 months; P<0.001 for trend). Among converters, surgical resection was consistently associated with additional survival benefit after IPTW adjustment [OS: HR =0.28; progression-free survival (PFS): HR =0.39]. Conclusions: Successful conversion is a strong prognostic marker that identifies a pivotal window for intervention in selected patients with uHCC; within this window, surgery resection is associated with the greatest survival advantage. This study provides a methodological framework for reliably evaluating conversion therapy outcomes in real-world settings.

Objective This study aims to develop and validate a comprehensive scoring system based on anatomical and clinical parameters to predict surgery duration, operative blood loss, and urinary control in patients undergoing laparoscopic radical prostatectomy (LRP). Methods This retrospective analysis included 361 patients with prostate cancer who underwent surgery performed by Xudong Yao. The study evaluated the correlation of variables such as height/weight ratio (HWR), prostate/pelvis ratio (PPR), retzius space (RS) size, intravesical prostatic protrusion (IPP), and prostate volume (PV). Based on these factors, the RRRIV scoring system was developed. The correlation between these variables and key outcomes (surgery duration, operative blood loss, and urinary function recovery) was then assessed in relation to the RRRIV score. Results Correlation analysis revealed significant positive associations between the RRRIV score and operative time (95% CI = 0.229(0.129-0.325), p < 0.001), operative blood loss (95% CI = 0.305(0.209-0.386), p < 0.001), and recovery of urinary function (95% CI = 0.381(0.289-0.466), p < 0.001). Furthermore, intergroup comparison showed that the medium and high-risk groups had significantly greater intraoperative blood loss, longer operative duration, and delayed recovery of urinary continence compared to the low-risk group. For the primary outcomes, the model demonstrated good discrimination, with an area under the curve ≥0.6. Conclusions The RRRIV scoring system provides a reliable method for predicting surgery duration, intraoperative blood loss, and recovery of urinary function in LRP, aiding surgeons in making more informed decisions during preoperative planning and patient discussions.

BackgroundUrolithiasis is a globally prevalent disease with a distinct male predominance; however, the pathophysiological heterogeneity within diagnosed cohorts remains underexplored. This study delineates the sex-specific signatures of gut microbiota and systemic inflammation in urolithiasis patients to inform sex-stratified management.MethodsThis cross-sectional study enrolled 60 urolithiasis patients (40 males, 20 females). Systemic inflammatory cytokines were quantified via peripheral blood assays, and gut microbiota was profiled using 16S rRNA sequencing. Data were integrated to evaluate microbiome-immune-metabolic associations.ResultsBaseline demographics and routine biochemical parameters were comparable between sexes. Male patients exhibited significantly elevated peripheral levels of pro-inflammatory cytokines, including IL-5, IL-17A, IFN-α, IL-12P70, and IFN-γ (P < 0.05). Beta-diversity analysis revealed no significant difference in the overall gut microbial community structures between sexes (P = 0.484). LEfSe analysis identified a significant enrichment of Akkermansia and Holdemanella in females, whereas Mogibacterium was notably enriched in males. Crucially, Mogibacterium abundance positively correlated with IL-17A and IL-12P70 levels (P < 0.05). Functional potential profiling indicated enhanced predicted capacities for secondary metabolite biosynthesis and lipid metabolism in the female cohort.ConclusionOur findings highlight significant sex-associated differences in gut microecology and systemic immune profiles within urolithiasis patients. The proinflammatory axis associated with male patients and the enhanced predicted metabolic capacities observed in female patients emphasize the potential value of exploring sex-tailored preventive and therapeutic interventions.

Spatial transcriptomics reveals cellular heterogeneity, intercellular communication, and tissue organization, but its cost and limited accessibility restrict clinical use. Here, we present VISTA, a model that integrates multi-scale histological features and spatial context to infer spatial gene expression from H&E stained tissue images. Across leave one section out cross validation and independent validation, VISTA robustly predicted thousands of genes and outperformed state-of-the-art methods. Beyond expression reconstruction, VISTA enabled clinically relevant downstream analyses. In TCGA breast cancer samples, it identified survival-associated genes, stratified prognostic risk groups, and revealed adverse tumor-associated spatial subtypes. In our inhouse intrahepatic cholangiocarcinoma cohort, it preserved tumor normal organization and identified CLDN4 and CYP3A4 as complementary spatial biomarkers. In HER2+ breast cancer, it predicted pathological response to neoadjuvant trastuzumab-based therapy and linked response-associated regions to immune and cytokine related programs. These results support virtual spatial transcriptomics from routine histopathology for oncology applications.

Colorectal mucinous adenocarcinoma (MAC), a distinct subtype of adenocarcinoma (AC) characterized by extracellular mucus production. However, the specific regulatory role of mucus production in MAC development remains underexplored. In this study, scRNA-seq analyses revealed that L1TD1 expression was significantly greater in MAC than in adjacent noncancerous tissues. L1TD1 is an RNA-binding protein that has been reported to regulate mRNA stability and stemness-associated transcriptional programs in cancer cells. Further experiments confirmed that L1TD1 expression was elevated in MAC compared to normal tissues and L1TD1 promoted mucus production and accelerated tumor cell proliferation and metastasis. Mechanistically, further analysis revealed the RNA recognition motif (RRM) domain of L1TD1 binds to the 3 ' untranslated region (3'-UTR) of ABCC3 mRNA, thus increasing its stability. In addition, ABCC3 inhibition reversed L1TD1 overexpression-induced mucus production and MAC progression. Collectively our findings demonstrate that L1TD1 binds to the GUGU motif within ABCC3 mRNA and upregulates ABCC3 expression, which subsequently activates the MAPK signaling pathway and promotes mucin production and accelerates MAC progression. These results also provide essential evidence for investigating the mechanisms of mucus production and tumor progression in MAC.

AbastractNephrolithiasis, particularly calcium oxalate (CaOx) stones, remains a global health burden with limited pharmacological options for recurrence prevention. In this study, we investigated the therapeutic mechanism of acacetin (ACA) using both in vitro (COM-stimulated HK-2 cells) and in vivo (glyoxylate-induced mice) models of CaOx kidney stone. Our results demonstrated that ACA treatment dose-dependently attenuated renal injury, reduced the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and activated the Nrf2/HO-1/NQO1 antioxidant pathway. Moreover, ACA significantly suppressed the NLRP3/caspase-1/GSDMD-mediated pyroptosis pathway. Through network pharmacology analysis, molecular docking, and molecular dynamics simulations, we identified GPR35 as a high-affinity direct binding target of ACA. The cellular thermal shift assay (CETSA) further confirmed that ACA enhanced the thermal stability of GPR35, indicative of direct interaction. Functional validation revealed that GPR35 overexpression recapitulated the protective effects of ACA by inhibiting NLRP3-related pyroptosis, whereas GPR35 knockdown significantly abrogated ACA-mediated pyroptosis suppression. Collectively, these findings establish the GPR35/NLRP3/pyroptosis axis as a critical pathway in CaOx kidney stone pathogenesis and identify ACA as a novel GPR35 agonist that concurrently suppresses pyroptosis and activates antioxidant defenses. Thus, ACA represents a promising therapeutic candidate for the prevention and treatment of kidney stone disease.

BackgroundSepsis continues to be a life-threatening complication following ureteroscopic lithotripsy (URSL). Available clinical prediction tools tend to be inadequate in their capacity to depict the underlying pathophysiology of sepsis-systemic immune-inflammatory imbalance. It is particularly difficult in patients who lack obvious preoperative microbiological findings. The study aims to evaluate the new Systemic Immune-Inflammatory Complex Index (SIICI) as well as other indices such as (SII, SIRI, PIV) in predicting post-URSL sepsis.MethodsWe performed a single-center retrospective study of 803 patients who underwent URSL. Multivariate logistic regression was used to create a clinical baseline model. To assess the incremental predictive value, each inflammatory index was added separately to the baseline model. The model performance was compared using the area under the ROC curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), likelihood ratio test (LRT) and decision curve analysis (DCA).ResultsThe “Base + SIICI” model was found to be the most effective among the four indices. It had the highest degree of discrimination (AUC = 0.863, 95% CI: 0.819-0.908), which is a considerable improvement over the baseline model (AUC = 0.807, p<0.001). There were meaningful improvements in reclassification (NRI = 0.133, p=0.001) and discrimination (IDI = 0.058, p=0.002), a significant likelihood ratio test (p<0.001) backed up these findings. The decision curve analysis confirmed that higher net clinical benefit was found at a larger variety of probability thresholds. Notably, the model performed well in individuals with negative preoperative urine cultures (AUC = 0.850). A visual nomogram was developed and validated based on this model, showing good calibration and a bootstrap-corrected AUC of 0.849. An online calculator was also created to facilitate clinical application.ConclusionSIICI is a new index that offers high incremental value in predicting sepsis after URSL compared to traditional indices like SII, SIRI and PIV. Nomogram based on SIICI presents a strong and useful instrument of early stratification of risks of development and can assist in making proactive clinical decisions, particularly where standard infection indicators cannot be used.

Sepsis is a serious complication after ureteroscopic lithotripsy (URSL), but its accurate pre-operative prediction remains difficult. This study aims to evaluate novel immunonutritional-inflammatory indices, which reflect the “nutrition-immunity-inflammation” axis, for predicting post-URSL sepsis. We conducted a retrospective cohort study of 569 patients undergoing URSL. Postoperative sepsis was diagnosed per Sepsis-3 criteria. A base clinical model was built using pre-operative variables from multivariate analysis. We then assessed the incremental predictive value of adding five indices (CALLY, PNI, CAR, NAR, NPAR) by evaluating discrimination (AUC), calibration, reclassification (NRI, IDI), and clinical utility (Decision Curve Analysis). A nomogram and web calculator were developed based on the CALLY-augmented model for clinical use. Of 569 patients, 41 (7.2

BackgroundUrinary tract infection is one of the most common comorbidities of urinary stones. Disorders of gut microbiota can affect various infectious diseases and the formation of the stones. Therefore, alterations in the gut bacteria profile may be a potential risk factor for the development of infections in patients with urinary tract stones.MethodsWe conducted a retrospective study to analyze the association of urinary tract infections with gut microbiota and serum metabolism in patients with stones.ResultsPatients with urolithiasis were predominantly in combination with diabetes mellitus (11.4% vs. 20%) and hypertension (36.4% vs. 50%). There were no statistically significant differences in hematological and urinary parameters. Compared to negative patients, IL-17A was significantly higher in the positive group (25.0 vs 21.1 pg/ml p = 0.038). The majority of pathogens detected in urine cultures were urease-negative bacteria, and urease-positive bacteria accounted for 15% of the total number of patients. We analyzed the community composition of the two groups of patients and found a significant difference in their β-diversity (p = 0.025), suggesting that dysbiosis of the gut bacteria may be associated with the combination of urinary tract infections in urolithiasis. For identification of crucial bacteria, we found changes in the abundance of both Intestinibacter (p = 0.036) and Dialister (p = 0.039), and abundance of Intestinibacter was positively correlated with IFN-α, IL-12P70 (p<0.05), and especially IL-17A (p<0.01), which may result from differences in translational, ribosomal structural and biosynthetic functions in stone patients (p < 0.05).ConclusionUrolithiasis with gut dysbiosis developed a higher incidence of urinary tract infections, which may be associated with the increasing of Intestinibacter and affect the expression of IL-17A by translational, ribosomal structural and biosynthetic function.

BACKGROUND:Urolithiasis is one of the most common urological diseases, and its incidence has increased globally in recent years. Multiple potential mechanisms are involved in urolithiasis, including renal oxidative stress, inflammatory response, fibrosis, pyroptosis, and gut microbiota disturbance. Sodium bicarbonate (NaHCO3) is commonly used clinically to alkalize urine and slow the progression of chronic kidney disease, including urolithiasis. However, the specific mechanism of NaHCO3 in the treatment of urolithiasis is unclear. METHODS:In this study, we constructed a mice urolithiasis model via intraperitoneal injection of glyoxylate (50 mg/kg) for one week in C57BL/6 mice. Meanwhile, 5% NaHCO3 was added to drinking water in the treatment group. Biochemical detection, immunohistochemical staining, RT-qPCR, and Western blotting were used to assess kidney function and levels of inflammation and pyroptosis. The alteration of gut microbiota in mice treated with NaHCO3 was measured using 16S rDNA sequencing. RESULTS:The results demonstrated that NaHCO3 effectively reduced the deposition of CaOx crystal, as well as restored kidney function in urolithiasis-induced kidney injury mice. Moreover, NaHCO3 alleviated oxidative stress and inflammatory response and ameliorated pyroptosis by modulating the NLRP3 inflammasome pathway in kidney. Additionally, it enhanced the intestinal barrier function by up-regulating the expression of tight junction proteins (ZO-1, occludin, and claudin 5), remodeling the gut microbiota, and reducing intestinal inflammation. CONCLUSION:In summary, NaHCO3 exerted a protective effect via the gut-kidney axis in the urolithiasis mice model, suggesting its potential use as a dietary supplementation to be added to daily drinking water for the management of urolithiasis.