Background: Kidney stones are composed of approximately 70–80% calcium oxalate. However, the exact mechanism of formation of calcium oxalate kidney stones remains unclear. In this study, we investigated the roles of endoplasmic reticulum stress (ERS), reactive oxygen species (ROS), and the NF-κB signalling pathway in the pathogenesis of oxalate-induced renal tubular epithelial cell injury and its possible molecular mechanisms. Methods: We established a model to evaluate the formation of kidney stones by intraperitoneal injection of glyoxylic acid solution into mice and assessed cell morphology, apoptosis, and the expression levels of ERS, ROS, and NF-κB signalling pathway-related proteins in mouse renal tissues. Next, we treated HK-2 cells with potassium oxalate to construct a renal tubular epithelial cell injury model. We detected the changes in autophagy, apoptosis, and mitochondrial membrane potential and investigated the ultrastructure of the cells by transmission electron microscopy. Western blotting revealed the expression levels of apoptosis and autophagy proteins; mitochondrial structural and functional proteins; and ERS, ROS, and NF-κB (p65) proteins. Lastly, we studied the downregulation of NF-κB activity in HK-2 cells by lentivirus interference and confirmed the interaction between the NF-κB signalling and ERS/ROS pathways. Results: We observed swelling of renal tissues, increased apoptosis of renal tubular epithelial cells, and activation of the ERS, ROS, and NF-κB signalling pathways in the oxalate group. We found that oxalate induced autophagy, apoptosis, and mitochondrial damage in HK-2 cells and activated the ERS/ROS/NF-κB pathways. Interestingly, when the NF-κB signalling pathway was inhibited, the ERS/ROS pathway was also inhibited. Conclusion: Oxalate induces HK-2 cell injury through the interaction between the NF-κB signalling and ERS/ROS pathways.

Background: The morbidity of nephrolithiasis is 2–3 times higher in males than in females, suggesting that androgen plays a key role in nephrolithiasis. The death of renal tubular epithelial cells (TECs) is an important pathophysiological process contributing to the development of nephrolithiasis. Therefore, the aim of this study is to investigate whether androgen directly induces TECs apoptosis and necrosis and its underlying mechanisms in kidney stone formation. Materials and methods: We compared serum testosterone level between male and female healthy volunteers and kidney stone patients. The in vivo nephrolithiasis model was established using glyoxylic acid, and calcium deposits were detected by van Kossa staining. In the in vitro study using mouse TECs (TCMK-1 cells) and human TECs (HK-2 cells), apoptosis, necrosis, and the expression of BH3-only protein Bcl-2-like 19 kDa-interacting protein 3 (BNIP3) were examined incubated with different doses of testosterone using flow cytometry. Levels of apoptosis-related proteins transfected with the BNIP3 siRNA were examined by western blotting. The mitochondrial potential (ΔΨm) was detected by JC-1 staining and flow cytometry. We monitored BNIP3 expression in the testosterone-induced TECs injury model after treatment with hypoxia inducible factor 1α (HIF-1α) and/or hypoxia inducible factor 2α (HIF-2α) inhibitors to determine the upstream protein regulating BNIP3 expression. Additionally, ChIP and luciferase assays were performed to confirm the interaction between HIF-1α and BNIP3. Results: Both male and female patients have significantly higher testosterones compared with healthy volunteers. More calcium deposits in the medulla were detected in male mice compared to female and castrated male mice. Testosterone induced TECs apoptosis and necrosis and increased BNIP3 expression in a dose-dependent manner. Testosterone also increased Bax expression, decreased Bcl-2 expression and induced a loss of ΔΨm. This effect was reversed by BNIP3 knockdown. HIF-1α inhibition significantly decreased BNIP3 expression and protected TECs from testosterone-induced apoptosis and necrosis. HIF-2α inhibition, however, did not influence BNIP3 expression or TECs apoptosis or necrosis. Finally, HIF-1α interacted with the BNIP3 promoter region. Conclusion: Based on these results, testosterone induced renal TECs death by activating the HIF-1α/BNIP3 pathway.

Objectives: To establish a predictive model for sepsis after percutaneous nephrolithotomy (PCNL) using machine learning to identify high-risk patients and enable early diagnosis and intervention by urologists. Methods: A retrospective study including 694 patients who underwent PCNL was performed. A predictive model for sepsis using machine learning was constructed based on 22 preoperative and intraoperative parameters. Results: Sepsis occurred in 45 of 694 patients, including 16 males (35.6%) and 29 females (64.4%). Data were randomly segregated into an 80% training set and a 20% validation set via 100-fold Monte Carlo cross-validation. The variables included in this study were highly independent. The model achieved good predictive power for postoperative sepsis (AUC = 0.89, 87.8% sensitivity, 86.9% specificity, and 87.4% accuracy). The top 10 variables that contributed to the model prediction were preoperative midstream urine bacterial culture, sex, days of preoperative antibiotic use, urinary nitrite, preoperative blood white blood cell (WBC), renal pyogenesis, staghorn stones, history of ipsilateral urologic surgery, cumulative stone diameters, and renal anatomic malformation. Conclusion: Our predictive model is suitable for sepsis estimation after PCNL and could effectively reduce the incidence of sepsis through early intervention.

Introduction: To investigate the ablation efficiency of super-pulse thulium fiber laser (SPTFL) with different laser settings and fiber usage. Materials and Methods: SPTFL machine was attached with different fibers. Artificial stones were fixed in water, whereas laser fiber was driven on a platform for ablation. Pulse energy, frequency, fiber-moving speed, fiber-to-stone distance, and fiber size were adjusted in each trial. The cross-sectional area of craters on the lateral stone surface was measured for comparison of ablation rate, combined with fiber-moving speed. Results: There was a trend that the ablation rate increased as pulse energy or frequency increased. When pulse energy was set as 0.2 J and frequency was increased from 50 to 150 Hz, the cross-sectional area of the crater was enlarged from 0.21 to 0.37 mm ² ( p < 0.05); when the frequency was set as 100 Hz and pulse energy was increased from 0.1 to 0.3 J, the crater was enlarged from 0.10 to 0.45 mm ² ( p < 0.05). Furthermore, energy demonstrated greater impact on ablation rate and the crater was enlarged from 0.20 mm ² in the 0.1 J × 300 Hz group to 0.44 mm ² in the 0.3 J × 100 Hz group ( p < 0.05). Then fiber was set at different moving speeds with the same laser setting; the ablation rate of 3 mm/second group was 3.64 times higher than 0.5 mm/second group ( p < 0.05). Ablation diminished as fiber-to-stone distance grew. A 200 μm fiber produced thinner and deeper fissure than 272 and 550 μm fibers, and the ablation rate was the highest for the 200 μm fiber. Conclusion: Pulse energy is a more important factor in influencing ablation efficiency compared with frequency. Closer fiber-to-stone distance, faster fiber movement, and smaller fiber size increase ablation efficiency.