A novel post-percutaneous nephrolithotomy sepsis prediction model using machine learning.

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.

Development and validation of the UCSS score, a novel method to predict septic shock after PCNL.

OBJECTIVE: To develop an objective and easily recognizable model to predict septic shock following percutaneous nephrolithotomy (PCNL). SUBJECTS AND METHODS: First, we identified differences between 431 patients who underwent PCNL with or without septic shock. These data were used to develop existing models and examine their improvement. Multivariate analysis was applied to identify risk factors of septic shock after PCNL based on the scores allocated to the PCNL postoperative test indicators. Finally, we developed a predictive nomogram using the selected factors and compared its performance with that of the existing nomograms SOFA, qSOFA, and SIRS. RESULTS: Twelve (2.8%) of the patients met the criteria for postoperative septic shock after PCNL. Baseline data analysis revealed differences in sex, preoperative drainage, urinary culture, and urinary leukocyte between groups. After transforming patient data into measurement-level data, we investigated each index score in these conditions, and found that the incidence of septic shock generally increased with the score. Multivariate analysis and early optimization screening revealed that septic shock factors could be predicted using platelets, leukocytes, bilirubin, and procalcitonin levels. We further compared the prediction accuracy of urinary calculi-associated septic shock (UCSS), SOFA, qSOFA, and SIRS scores using the AUC of the ROC curve. As compared to SIRS [AUC 0.938 (95% CI 0.910-0.959)] and qSOFA [AUC 0.930 (95% CI 0.901-0.952)], UCSS [AUC 0.974 (95% Cl 0.954-0.987)] and SOFA [AUC 0.974 (95% CI 0.954-0.987)] scored better at discriminating septic shock after PCNL. We further compared the ROC curves of UCSS with SOFA (95% CI - 0.800 to 0.0808, P = 0.992), qSOFA (95% CI - 0.0611 to 0.0808, P = 0.409), and SIRS (95% CI - 0.0703 to 0.144, P = 0.502), finding that UCSS was non-inferior to these models. CONCLUSIONS: UCSS, a new convenient and cost-effective model, can predict septic shock following PCNL and provide more accurate discriminative and corrective capability than existing models by including only objective data. The predictive value of UCSS for septic shock after PCNL was greater than that of qSOFA or SIRS scores.

Oxalate-induced apoptosis through ERS-ROS-NF-κB signalling pathway in renal tubular epithelial cell.

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.

Performance of SOFA, qSOFA and SIRS to predict septic shock after percutaneous nephrolithotomy.

OBJECTIVE: The new clinical criteria termed SOFA and qSOFA were demonstrated to be more accurate than SIRS in screening patients at high risk of sepsis. We aim to evaluate the ability of SOFA, qSOFA and SIRS to predict septic shock after PCNL. PATIENTS AND METHODS: Consecutive patients undergoing PCNL were included to assess the performance of SOFA, qSOFA and SIRS in predicting septic shock, the AUC of ROC curve and decision curve analysis were used, and the optimal cutoff values and their achieving time were calculated. RESULTS: Of the 431 included patients, 12 (2.7%) cases developed septic shock. Compared with non-septic shock patients, patients with septic shock were more likely to be female, have positive history of urine culture and higher urine leukocyte count, and show increased postoperative serum creatinine, PCT and decreased leukocyte. The optimal cutoff of SOFA, qSOFA and SIRS was > 2, > 0 and > 1, respectively. All of the 12 patients with verified septic shock met SOFA and SIRS criteria, while only 11 cases met qSOFA criterion. SOFA had the identical highest sensitivity (100%) and greater specificity (87% vs. 81%) than SIRS. qSOFA had higher specificity (92%) than both SOFA and SIRS at the expense of lower sensitivity (92%). The AUC of SOFA (0.973) to predict septic shock was greater than that of qSOFA (0.928) and SIRS (0.935). When combined with SIRS, SOFA outperformed qSOFA for discrimination of septic shock (AUC 0.987 vs. 0.978). Decision curve analysis indicated SOFA was clearly superior to both qSOFA and SIRS with a higher net benefit and net reduction in intervention. The qSOFA achieved the best time-based predictive efficiency, with the shortest median time to meet its cutoff, followed by SOFA and SIRS. CONCLUSION: The performance of SOFA in predicting septic shock after PCNL was slightly greater than qSOFA and SIRS. The comprehensive application of various criteria is recommended to assist early detection of septic shock following PCNL.

Risk factors for sepsis in patients with struvite stones following percutaneous nephrolithotomy.

PURPOSE: To describe the clinical characteristics of struvite stones and determine the preoperative predictors of sepsis in struvite patients undergoing percutaneous nephrolithotomy (PCNL). METHODS: A retrospective study of patients who underwent PCNL between April 2011 and March 2018 was performed. The data of the struvite stones and non-struvite stones groups were compared following propensity score matching. Subsequently, the struvite stones group was sub-divided for further analysis according to the Sepsis-3 definition: non-sepsis and sepsis groups. RESULTS: After matching based on age, gender, BMI, and number of access tracts, the comparative analysis showed that staghorn calculi and higher Guy's stone score were more frequently observed in non-struvite stone patients (n = 97), while a history of urolithiasis surgery (56.70%), preoperative broad-spectrum antibiotic therapy (53.61%), positive preoperative urine culture (55.67%), and sepsis (35.05%) after surgery were more common in patients (n = 97) with struvite stones (all P values < 0.05). Eighteen (18.56%) patients presented with multidrug-resistant (MDR) bacteriuria. Multivariate analysis demonstrated that the preoperative presence of MDR bacteriuria (OR = 3.203; P = 0.043) and increased serum creatinine (OR = 3.963; P = 0.010) were independent risk predictors of sepsis. The two factors were used to construct a nomogram to predict the probability of sepsis. The nomogram was well calibrated and had moderate discriminative ability (concordance index: 0.711). CONCLUSION: Our study revealed that patients with struvite stones were associated with a significantly high risk of calculi recurrence and sepsis after surgery. The presence of MDR bacteriuria preoperatively was a reliable factor to predict sepsis.

Testosterone induces renal tubular epithelial cell death through the HIF-1α/BNIP3 pathway.

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.

IgG4-related disease of the ureter mimicking malignant ureter tumor: a case report and experience sharing.

Background: Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disease that can affect any organ or tissue in the body, and is characterized by intensive infiltration of IgG4-positive plasma cells, and elevated serum IgG4 levels. IgG4-RD causes renal impairment of unknown pathogenesis that may progress to kidney failure. However, few case of IgG4-RD mimicking malignant ureter tumor leading to severe hydronephrosis. Case Description: This report describes a 38-year-old male patient who was hospitalized for sudden waist pain. Enhanced abdominal computed tomography (CT) revealed a mass involving the right ureter. He presented to the urologist with severe right hydronephrosis. Urinalysis revealed occult blood (3+), and atypical cells were observed in urine cytology, raising the possibility of a ureteral malignancy. After that, the patient underwent diagnostic ureteroscopy instead of direct nephroureterectomy and was found not to have any malignancy. The patient received laparoscopic partial ureteral resection and anastomosis. Histologically, there were observations of IgG4-positive plasma cell infiltration exceeding 10 cells per high-power field, as well as a high ratio of IgG4-positive/IgG-positive cells exceeding 40%. And histopathology revealed ureteral IgG4-related disease, with no evidence of urothelial carcinoma. Conclusions: IgG4-RD has previously been reported in lesions involving the ureters, but misdiagnosis and subsequent radical nephroureterectomy can cause lifelong regret for the patient in having lost one side of the urinary tract. To avoid such misdiagnoses, clinicians should consider IgG4-RD as a potential condition.

Porous Se@SiO2 nanocomposites play a potential inhibition role in hyperoxaluria associated kidney stone by exerting antioxidant effects.

Background: Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO2 groups (Se@SiO2 6.905±0.074 mg/kg; GAM + Se@SiO2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.

Inhibition of EZH2 ameliorates hyperoxaluria-induced kidney injury through the JNK/FoxO3a pathway.

AIMS: Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, has been shown to play a role in kidney diseases. However, its role in hyperoxaluria-induced renal tubular epithelial cells (TECs) injury remains unclear. MATERIALS AND METHODS: A hyperoxaluria rat model was established by providing 0.5% ammonium chloride and drinking water containing 1% ethylene glycol. TECs were exposed to oxalate stress. The 3-DZNeP, a selective EZH2 inhibitor, was administered in vivo and in vitro. Cell viability, ROS production, and apoptosis ratio were evaluated. Crystal deposition was detected by Von Kossa staining and kidney tissue injury was detected by HE staining and TUNEL. EZH2, H3K27me3, cleaved-caspase3, IL-6, and MCP-1 were examined by western blot or immunohistochemistry. KEY FINDINGS: Inhibition of EZH2 by 3-DZNeP significantly attenuated hyperoxaluria-induced oxidative and inflammatory injury and CaOx crystal deposition in vivo. Similarly, inhibition of EZH2 using 3-DZNeP or shRNA restored cell viability, suppressed LDH release and the production of intracellular ROS in vitro. Furthermore, the MAPK signaling pathway and FoxO3a levels were activated or elevated in TECs exposed to oxalate. EZH2 inhibition using 3-DZNeP blocked these effects. CC90003 (ERK inhibitor) or SB203580 (p38 inhibitor) did not significantly affect the expression of FoxO3a in TECs treated with 3-DZNeP and oxalate; only SP600125 (JNK inhibitor) significantly decreased FoxO3a expression. SIGNIFICANCE: EZH2 inhibition protects against oxalate-induced TECs injury and reduces CaOx crystal deposition in the kidney may by modulating the JNK/FoxO3a pathway; EZH2 may be a promising therapeutic target in TECs injury.

Gender-related differences in the performance of sequential organ failure assessment (SOFA) to predict septic shock after percutaneous nephrolithotomy.

The study aims to identify whether gender differences exist in the sequential organ failure assessment (SOFA) score to the extent of affecting its predictive accuracy for septic shock after percutaneous nephrolithotomy (PCNL). A retrospective study of 612 patients undergoing PCNL was performed. The SOFA scores of male and female groups were compared to identify any gender differences. The ROC curve was used to find differences between the original and adjusted SOFA scores. Postoperative septic shock developed in 21 (3.43%) cases. A marginally significant discrepancy in median SOFA scores between genders was discovered in a subgroup of patients < 40 years old (p = 0.048). A gender difference existed in the SOFA score after PCNL, with greater proportion of high scores in female patients (p = 0.011). Male patients had a higher proportion of ≥ 2 sub-score in hepatic and renal systems than female patients, caused by their higher preoperative bilirubin and creatinine (p < 0.05). An adjusted SOFA score was created to replace the original postoperative SOFA score with the perioperative changed values of bilirubin and creatinine. Performance of the adjusted SOFA score for predicting septic shock was comparable with the original SOFA score (AUC 0.987 vs. 0.985, p = 0.932). Under the premise of ensuring 100% sensitivity, the adjusted SOFA score reduced the 43.7% (31/71) false-positive rate for predicting septic shock compared with the original SOFA score. In conclusion, the gender should not be neglected when applying SOFA score for patients after PCNL. The adjusted SOFA score eliminates negative effects caused by gender differences in predicting septic shock.

Ablation Efficiency of a Novel Thulium Fiber Laser: An In Vitro Study on Laser Setting and Fiber Usage.

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 mm2 (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 mm2 (p < 0.05). Furthermore, energy demonstrated greater impact on ablation rate and the crater was enlarged from 0.20 mm2 in the 0.1 J × 300 Hz group to 0.44 mm2 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.

An Immune Atlas of Nephrolithiasis: Single-Cell Mass Cytometry on SIRT3 Knockout and Calcium Oxalate-Induced Renal Injury.

BACKGROUND: As a common urological disease with a high recurrence rate, nephrolithiasis caused by CaOx may elicit a strong immunologic response. We present a CyTOF-based atlas of the immune landscape in nephrolithiasis models to understand how the immune system contributes to, and is affected by, the underlying response caused by SIRT3 knockout and CaOx inducement. MATERIALS AND METHODS: We performed a large-scale CyTOF analysis of immune cell abundance profiles in nephrolithiasis. The immunophenotyping data were collected from four different mouse models, including the SIRT3 wild-type or knockout, including and excluding CaOx inducement. Unsupervised analysis strategies, such as SPADE and viSNE, revealed the intrarenal resident immune components and the immune alterations caused by SIRT3 knockout and CaOx-induced renal injury. RESULTS: An overview analysis of the immune landscape identified T cells and macrophages as the main immune cell population in nephrolithiasis models. Highly similar phenotypes were observed among CD4+ and CD8+ T cell subsets, including cells expressing Ki67, Ly6C, Siglec-F, and TCRß. Macrophages expressed a characteristic panel of markers with varied expression levels including MHC II, SIRPα, CD11c, Siglec-F, F4/80, CD64, and CD11b, indicating more subtle differences in marker expression than T cells. The SIRT3KO/CaOx and SIRT3WT/CaOx groups exhibited global differences in the intrarenal immune landscape, whereas only small differences existed between the SIRT3KO/CaOx and SIRT3KO/Ctrl groups. Among the major immune lineages, the response of CD4+ T cells, NK cells, monocytes, and M1 to CaOx inducement was regulated by SIRT3 expression in contrast to the expression changes of B cells, DCs, and granulocytes caused by CaOx inducement. The panel of immune markers influenced by CaOx inducement significantly varied with and without SIRT3 knockout. CONCLUSION: In a CaOx-induced nephrolithiasis model, SIRT3 has a critical role in regulating the immune system, especially in reducing inflammatory injury. The characteristic panel of altered immune clusters and markers provides novel insights leading to improved prediction and management of nephrolithiasis.

Retraction Note: Sirt3 suppresses calcium oxalate-induced renal tubular epithelial cell injury via modification of FoxO3a-mediated autophagy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Safety of a Novel Thulium Fiber Laser for Lithotripsy: An In Vitro Study on the Thermal Effect and Its Impact Factor.

Introduction: To investigate the thermal effect on the water by a novel thulium fiber laser (TFL) designed for lithotripsy and evaluate the safety of this laser for clinical use. Materials and Methods: An in vitro experimental setup was constructed. A test tube filled with saline was immersed in an electric water bath, and a TFL fiber and a thermal probe were inserted into it. Saline was irrigated into the tube and pumped out synchronously at the same speed by two pumps, respectively, to maintain convection when needed. Then, continuous TFL firing of different power settings was imposed to saline in the tube for 60 seconds, on the conditions of different irrigation rates. The temperature was recorded every 5 seconds during the whole trial, and each trial was repeated five times. Safety threshold of temperature increase (STTI) was determined comparing with the deemed safe temperature of 43°C in vivo. Results: On condition of 0 mL/min irrigation rate, STTI was 6.5°C, and water temperature increase (WTI) caused by ≥15 W settings surpassed STTI after 20 seconds of laser firing; on condition of 15 mL/min irrigation rate, only WTI caused by the highest 30 W power setting surpassed STTI after 45 seconds of laser firing. When irrigation rate was added up to 25 and 50 mL/min, WTIs caused by all power settings were below STTIs in a 60-second experiment. High frequency and low pulse energy combinations caused a slightly higher WTI compared with low frequency and high pulse energy, given a constant power and irrigation rate. Conclusion: Power setting and irrigation rate collaboratively play a critical role in WTI during TFL lithotripsy, and it is safe to use TFL referring to the thermal effect as long as there is moderate irrigation, while TFL power should be lowered enough when irrigation is ceased.

Apoptosis of human kidney epithelial cells induced by high oxalate and calcium oxalate monohydrate is apurinic/apyrimidinic endonuclease 1 pathway dependent and contributes to kidney stone formation.

Kidney stone formation is a very complex process. Multiple molecules and proteins are involved in its formation. High level of oxalate and calcium oxalate monohydrate (COM, 200 mg/ml) crystals are key elements for this process, but the exact mechanism needs to be defined. HOA has been shown to cause renal cell injury through oxidative stress, leading to potential crystal deposition in the kidneys, which induced apoptosis of kidney epithelial cells. Recent reports indicated that apurinic/apyrimidinic endonuclease 1 (APE1) is involved in DNA repair and redox regulation of transcriptional factors, and APE1-dependent apoptosis is observed in various nephropathy models. Therefore, we investigated the changes of APE1 protein expression in the human kidney epithelial cell line (HK-2) by exposing them to high oxalate and COM in various conditions. The results showed that HOA triggers intracellular reactive oxygen species (ROS) and apoptosis of HK-2 cells. This process was mediated by the abnormal expression, modification, and redistribution of APE1 protein in HK-2 cells. The antioxidant N-acetylcysteine reversed this effect. Our results demonstrated a novel molecular mechanism related to renal epithelial cell injury and kidney stone formation.

Current Treatment for Low-Risk Prostate Cancer in China: A National Network Survey.

Objective: To analyze the current treatment for low-risk prostate cancer (LRPC) in China. Methods: A national questionnaire survey titled "A survey of current treatment of LRPC" was designed and released nationally through the network from July 16 to August 3, 2017. Results: A total of 1,116 valid questionnaires were recovered. The percentages of preferred treatment by active surveillance (AS) or radical prostatectomy (RP) were 29.21% and 45.61%, respectively. A correspondence analysis showed that the physician in charge was more inclined to choose AS than RP. Respondents from different institution types, hospitals with different annual numbers of newly admitted patients with prostate cancer, and with different familiarity with the LRPC definition presented a significant difference in the preferred treatments (p < 0.05). Urologists chose AS or not for the following reasons: tumor progression (52.51%), potential medical disputes (42.56%) (i.e., medical disputes from patients or their relatives when urologists choose AS to treat patients with LRPC and the patient has a poor outcome), fear of cancer (41.94%), and surgical risk (39.07%). These reasons were ubiquitous, and there was no significant difference among urologists for these concerns (p > 0.05). Personal skills, surgical risk, and tumor progression were the most common factors that influenced whether AS or RP was preferred (p < 0.05). Concern about the medical disputes brought about by AS was a key factor for not choosing AS (p < 0.05). Conclusions: LRPC is still dominated by RP in China, followed by AS. Personal skills, surgical risk, and concern about tumor progression were the common factors influencing whether AS or RP was preferred. In addition, medical disputes brought by AS are another key factor for not choosing AS. There will be more Chinese data in the future to guide treatment of LRPC.

Sirt3 suppresses calcium oxalate-induced renal tubular epithelial cell injury via modification of FoxO3a-mediated autophagy.

High oxalic acid and calcium oxalate (CaOx)-induced renal tubular epithelial cell (TEC) injury plays a key role in nephrolithiasis. However, the mechanism remains unknown. Gene array analysis of the mice nephrolithiasis model indicated significant downregulation of sirtuin 3 (Sirt3) and activation of mitogen-activated protein kinase (MAPK) pathway. Kidney biopsy tissues of renal calculi patients also showed decreased Sirt3 expression. Silencing Sirt3 exacerbated oxidative stress and TEC death under CaOx stimulation. Restoring Sirt3 expression by overexpression or enhancing its activity protected renal function and reduced TEC death both in vitro and in vivo. Inhibiting the MAPK pathway resulted in upregulation of Sirt3 expression, preservation of renal function and decreased cell death both in vitro and in vivo. Furthermore, Sirt3 could upregulate FoxO3a activity post-translationally via deacetylation, dephosphorylation and deubiquitination. FoxO3a was found to interact with the promoter region of LC3B and to increase its expression, enhancing TEC autophagy and suppressing cell apoptosis and necrosis. Taken together, our results indicate that the MAPK/Sirt3/FoxO3a pathway modulates renal TEC death and autophagy in TEC injury.

Endoscopic Balloon Dilatation in the Treatment of Benign Ureteral Strictures: A Meta-Analysis and Systematic Review.

BACKGROUND AND PURPOSE: Although balloon dilatation is one of the main endoscopic procedures used to treat benign ureteral strictures, its precise efficacy remains controversial. We aimed to identify, combine, and analyze existing published data to ascertain the efficacy of endoscopic balloon dilatation for benign ureteral strictures. METHODS: In December 2018, a literature search was performed using Medline, Embase, and Web of Science databases. We included reports in which the study population consisted of patients who underwent endoscopic balloon dilatation for the treatment of benign ureteral strictures. Technical, short-term, and long-term success rates (expressed as mean ± standard error) were adopted as the outcome measures. RESULTS: Using our search strategy, a total of 19 studies (all series reports) were included for analysis. Using a random-effects model, the pooled technical success rate of endoscopic balloon dilatation for benign ureteral strictures was found to be 89% ± 4%. Furthermore, the short-term success rate (i.e., 3 months after surgery) was 60% ± 10%, and the long-term success rate (i.e., 6-12 months after surgery) was 54% ± 14%. In the subgroup analysis, the success rate of endoscopic balloon dilatation for ≤2-cm benign ureteral strictures was significantly higher than that for >2-cm ones (odds ratio [OR]: 0.13; 95% confidence interval [CI]: 0.05-0.35). In addition, the success rate in cases with strictures of onset timing ≤3 months was relatively higher than that in cases with strictures of onset timing >3 months (OR: 0.46; 95% CI: 0.15-1.43). CONCLUSION: Our study indicates that endoscopic balloon dilatation has a high success rate in the treatment of benign ureteral strictures with length ≤2 cm and onset timing ≤3 months. However, there is still no consensus on balloon type, dilatation pressure, expansion number, postoperative ureteral stent type, and stent retention time for the balloon dilatation technique.