BackgroundUpper tract urothelial carcinoma (UTUC) is a rare but highly invasive urinary malignancy with a high postoperative recurrence rate.MethodsWe retrospectively collected data from 133 UTUC patients who underwent radical nephroureterectomy between 2005 and 2017. Patients were divided into a training set (n=103) and a testing set (n=30). A multi-modal deep learning model named Multi-modal Image-Clinical Combination Classifier (MICC) was developed by integrating multi-phase contrast-enhanced CT imaging and clinical data. The model’s prognostic performance was compared with two unimodal models—ImageNet (CT-based) and ClinicalNet (clinical data-based)—and traditional clinical parameters including pathological T stage. Feature importance was evaluated using SHapley Additive exPlanations (SHAP).ResultsThe MICC model achieved superior prognostic accuracy with AUCs of 0.918 and 0.895 in the training and testing sets, respectively, outperforming unimodal models. Classification metrics were robust, with accuracy of 0.854, sensitivity of 0.889, specificity of 0.836, negative predictive value (NPV) of 0.933, and positive predictive value (PPV) of 0.744. Precision-recall analysis confirmed strong identification of high-risk patients despite dataset imbalance. SHAP analysis highlighted that CT imaging features contributed most significantly to the model’s predictions.ConclusionIntegrating multi-phase CT imaging with clinical data, the MICC model provides accurate prognostic prediction for UTUC patients. This approach has potential to assist clinicians in personalized risk stratification and treatment planning, ultimately improving patient outcomes.

The ergonomic aspects of retrograde intrarenal stone surgery (RIRS) remain underexplored, despite their crucial role in minimizing musculoskeletal strain among surgeons and enhancing procedural efficiency. This study introduces a novel “Gun-holding” surgical posture for RIRS, aiming to improve surgeons’ physical well-being and extend their operative careers. From July 2023 to June 2024, a total of 60 patients were prospectively enrolled from an initial pool of 104 and were randomized into two groups: the “Gun-holding” surgical posture group (Group A, n = 30) and the conventional surgical posture group (Group B, n = 30). Patient demographics, clinical outcomes, ergonomic assessments, and torque analysis for surgeons were analyzed. Baseline characteristics and stone burden were comparable between the two groups. Torque analysis demonstrated a higher upper limb torque ratio in Group A compared to Group B. Ergonomic evaluation revealed a significant advantage for Group A (total score: 16.1 ± 4.1 vs. 22.4 ± 9.1, P = 0.001). Group A also had a significantly shorter mean hospitalization duration (1.7 ± 0.9 days vs. 2.9 ± 1.9 days, P = 0.003). Although the mean operative time for Group A was shorter (49.9 ± 26.1 min vs. 63.0 ± 40.4 min), this difference was not statistically significant (P = 0.139). No significant differences were observed in initial stone-free status (SFS), 3-month SFR, postoperative Day 1 hemoglobin drop, or overall complication rates. The “Gun-holding” surgical posture is a feasible, efficient, and safe alternative for performing RIRS, offering significant ergonomic benefits to surgeons.

Several mechanisms underlying nephrolithiasis, one of the most common urological diseases, involve calcium oxalate formation, including oxidative stress, inflammatory reactions, fibrosis, pyroptosis, and apoptosis. Although lycopene has strong antioxidant activity, its protective effects against CaOx-induced injury have not yet been reported. This study aimed to systematically investigate the protective effects of lycopene and explore its mechanisms and molecular targets. Crystal deposition, renal function, oxidative stress, inflammatory response, fibrosis, pyroptosis, and apoptosis were assessed to evaluate the renoprotective effects of lycopene against crystal formation in a CaOx rat model and oxalate-stimulated NRK-52E and HK-2 cells. Lycopene markedly ameliorated crystal deposition, restored renal function, and suppressed kidney injury by reducing oxidative stress, apoptosis, inflammation, fibrosis, and pyroptosis in the rats. In cell models, lycopene pretreatment reversed reactive oxygen species increase, apoptotic damage, intracellular lactate dehydrogenase release, cytotoxicity, pyroptosis, and extracellular matrix deposition. Network pharmacology and proteomic analyses were performed to identify lycopene target proteins under CaOx-exposed conditions, and the results showed that Trappc4 might be a pivotal target gene for lycopene, as identified by cellular thermal shift assay and surface plasmon resonance analyses. Based on molecular docking, molecular dynamics simulations, alanine scanning mutagenesis, and saturation mutagenesis, we observed that lycopene directly interacts with Trappc4 via hydrophobic bonds, which may be attributed to the PHE4 and PHE142 residues, preventing ERK1/2 or elevating AMPK signaling pathway phosphorylation events. In conclusion, lycopene might ameliorate oxalate-induced renal tubular epithelial cell injury via the Trappc4/ERK1/2/AMPK pathway, indicating its potential for the treatment of nephrolithiasis.

Objective To develop a sensitive and fast detection method via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to assess the concentration of ajuforrestin A, ajuforrestin B, ajugamacrin and 8-O-Acetylharpagide primarily derived from Ajuga plants in mice blood and their pharmacokinetics. Methods Single protein precipitation with high-proportioned acetonitrile is chosen for sample clean-up. The UPLC HSS T3 (2.1 mm x 100 mm, 1.8 mu m) column with a mobile phase in gradient elution mode at the flow rate of 0.4 mL/min was used for sample separation. Acetonitrile was selected as the organic phase solution and water containing 0.1% formic acid was chosen as the aqueous solution. A tandem mass spectrometer containing an electrospray ionization (ESI) source in the positive ionization mode was used to detect four compounds via multiple reaction monitoring (MRM). Results The calibration curves (5-1000 ng/mL) of four compounds were linear with correlation coefficients > 0.997. The matrix effects, accuracy, precision, and recovery were all within permissible scope. Conclusions In this approach, the corresponding pharmacokinetic parameters were successfully clarified in mouse for the first time, which provided a theoretical basis for the improvement of the standard of Ajuga plants and the safety of clinical medication. Furthermore, this method may provide the UPLC-MS/MS evidence for the differentiation of the main close relative varieties of genus Ajuga according to these plants contain different mixtures of the four marker compounds.

Background: Nephrolithiasis is one of the most common urologic diseases with a high recurrence rate that causes a significant health and financial burden. Several mechanisms are involved in kidney calcium oxalate stone formation, including inflammation, oxidative stress, and apoptosis, e.g. Nevertheless, lycopene, a carotenoid compound that possesses many biological and pharmacological properties, including antioxidant and anti-inflammatory effects, has not been investigated in nephrolithiasis. Additionally, the role of pyroptosis, a lytic form of programmed cell death initiated by inflammasomes in nephrolithiasis has rarely been reported in rats with hyperoxaluria.Purpose: We aimed to systematically investigate the protective effects and potential mechanisms of lycopene in nephrolithiasis, and related role of pyroptosis in this process in vivo and in vitro.Methods: A rat model of hyperoxaluria was established by gavage of drinking water containing 1% ethylene glycol (EG) and 0.5% ammonium chloride (AC). A model of renal tubular epithelial cells (TECs) was established using oxalic acid. Crystal deposition, tubular injury, and apoptosis were detected by Von Kossa staining, HE staining, and TUNEL staining, respectively. Oxidative stress level, cell viability, expression levels of pyroptosis-related proteins (GSDMD, NLRP3, IL-1β, caspase-1), OPN, and IL-6 were assessed in TECs. In addition, the potential pathways and expression of key molecules were determined using western blotting.Results: In vivo, lycopene ameliorated crystal deposition, tubular injury, and apoptosis and decreased ROS production by increasing SOD, CAT, and GSH levels and reducing MDA levels induced by hyperoxaluria. Lycopene also reversed the expression of pyroptosis-related proteins, GSDMD, NLRP3, mature IL-1β, cleaved-caspase1, and the expression of OPN, IL-6, and cleaved-caspase3, which were increased in the calcium oxalate crystal group. Furthermore, we also found that cell viability was impaired and intracellular LDH release and pyroptosis-related proteins expression level in TECs were increased by oxalate in vitro, which was reversed by lycopene. Moreover, the phosphorylation of ERK, JNK, and P38 significantly increased and the protein expression of NOX1, NOX2, and NOX4 was elevated in TECs stimulated by oxalate in vitro. Lycopene inhibited the activation of MAPK pathway and selectively suppressed the protein expression of NOX1 and NOX4 without changing the NOX2 expression level.Conclusion: Lycopene may ameliorate oxalate-induced TECs injury by inhibiting pyroptosis, apoptosis, inflammatory response, and oxidative reaction by repressing the MAPK pathway, NOX1, and NOX4. Additionally, we confirmed that GSDMD-related pyroptosis plays a key role in nephrolithiasis.

Introduction Prostate cancer (PCa) is one of the most common malignant tumors of the male urogenital system; however, the underlying mechanisms remain largely unclear. This study integrated two cohort profile datasets to elucidate the potential hub genes and mechanisms in PCa. Methods and Results Gene expression profiles GSE55945 and GSE6919 were filtered from the Gene Expression Omnibus (GEO) database to obtain 134 differentially expressed genes (DEGs) (14 upregulated and 120 downregulated) in PCa. Gene Ontology and pathway enrichment were performed using the Database for Annotation, Visualization, and Integrated Discovery, showing that these DEGs were mainly involved in biological functions such as cell adhesion, extracellular matrix, migration, focal adhesion, and vascular smooth muscle contraction. The STRING database and Cytoscape tools were used to analyze protein-protein interactions and identify 15 hub candidate genes. Violin plot, boxplot, and prognostic curve analyses were performed using Gene Expression Profiling Interactive Analysis, which identified seven hub genes, including upregulated expressed SPP1 and downregulated expressed MYLK, MYL9, MYH11, CALD1, ACTA2, and CNN1 in PCa compared with normal tissue. Correlation analysis was performed using the OmicStudio tools, which showed that these hub genes were moderately to strongly correlated with each other. Finally, quantitative reverse transcription PCR and western blotting were performed to validate the hub genes, showing that the abnormal expression of the seven hub genes in PCa was consistent with the analysis results of the GEO database. Discussion Taken together, MYLK, MYL9, MYH11, CALD1, ACTA2, SPP1, and CNN1 are hub genes significantly associated with PCa occurrence. These genes are abnormally expressed, leading to the formation, proliferation, invasion, and migration of PCa cells and promoting tumor neovascularization. These genes may serve as potential biomarkers and therapeutic targets in patients with PCa.

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.

Objective:Objectives The aim of the study is to evaluate the mechanical performance, safety and efficacy of the novel robotic-assistant flexible ureteroscopy system (Ra-fURS) under in vitro and in vivo environments.Methods:Combing with commercial flexible ureteroscopes, the novel Ra-fURS was used for the in vitro test and animal model operation in October 2020. The study included three sections. ①Basic mechanical performance assessment: including endoscope motion control (dual deflection, axial rotation and forward/backward distance), reaction time and fiber regulation. ②Simulated surgery in ex-vivo 3D-printing renal collecting system model: including completion rate and time of calyxes exploration, directional movement and laser fragmentation [gypsum models (0.5×0.5×0.5 cm) were used to stimulate kidney stones]. ③Intrarenal surgeries in animal models (two 5-month female Yorkshire white pigs). In total, 32 surgeries was performed (8 surgeons × 2 pigs × 2 kidneys/pig). In vivo assessments were carried out including: ①consuming time for Ra-fURS installation and offloading; ②completion rate and time of calyxes exploration; ③comfort score (ranging from 0-10) as compared to the manual f-URS, which was corresponding to each Ra-fURS surgery. In simulated surgery and animal surgery sections, 8 surgeons were enrolled in the study (group A 4 without flexible ureteroscopy experience; group B: 4 highly experienced), and results were compared between two groups.Results:Under the Ra-fURS control, the flexible ureteroscope movement in three degrees of freedom (forward / backward: + 11 to -11 cm, axial rotation + 225°to -225°; active duel-flection: + 270°to -270°, as well as the laser fiber regulation + 2.5 to -2.5 cm). In simulated surgery tests, both groups achieved 100% completion rate of calyxes exploration, and there were no statistical differences in the time of the calyxes exploration between group A and group B (116.0±8.0)s vs.(110.3±15.4)s( P>0.05). Time-consumption for laser fragmentation of group B was shorter than that of group A (525.8±58.5)s vs. (780.5±141.2)s( P<0.01). In animal surgery, the installation time of Ra-fURS gradually shortened within the first 7 cases was(234.0±43.0)s, and became comparable in the later 8-32 cases was(149.3±8.0)s. The average uninstall time was (43.9 ±5.9)s and was relatively stable. There were 51 renal calyxes in two pigs. It was higher for the completion rate of calyxes exploration in group B than in group A [(95.5±9.1)% vs. (59.1±9.1)%, P<0.05], and the exploration time was also statistically variant between the two groups group A and group B[(274.8±34.6)s vs.(127.3±18.2)s, P<0.05]. For all the operators, the comfort scores were favorable to the Ra-fURS as compared to the manual f-URS (8.9±0.3 vs. 5.9±1.1, P<0.05). Conclusions:This preliminary study demonstrated that the novel Ra-fURS was capable of controlling flexible ureteroscope to perform retrograde intrarenal surgery and fragmenting stones with laser. Besides, other features, including easy installation, stable performance and comfortable manipulating environment, made it easy to use in clinical application.

The combination of hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been confirmed as an important risk biomarker in several cancers. Hence, we aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC in this study. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic (ROC) curve analysis. The relationship between postoperative survival outcomes and preoperative HALP level was assessed using Kaplan-Meier analysis and Cox regression analysis. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP<28.67 group and HALP≥28.67 group. Kaplan-Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (P<0.001) and progression-free survival (PFS) (P<0.001). Multivariate analysis demonstrated that lower HALP score was an independent risk factor for OS (HR=1.54, 95%CI, 1.14-2.01, P=0.006) and PFS (HR=1.44, 95%CI, 1.07-1.93, P=0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without. In the subgroup analysis, the HALP score could also stratify patients with respect to survival under different pathologic T stages. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.

The HALP score, which is the combination of hemoglobin, albumin, lymphocyte, and platelets has been confirmed as an important risk biomarker in several cancers. We aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). In this study, we retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic curve analysis. The relationship between post-operative survival outcomes and pre-operative HALP level was assessed using Kaplan-Meier and Cox regression analyses. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP <28.67 group and HALP ≥28.67 group. Kaplan–Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001). Multivariate analysis demonstrated that a lower HALP score was an independent risk factor for OS (HR = 1.54, 95% CI, 1.14-2.01, p = 0.006) and PFS (HR = 1.44, 95% CI, 1.07-1.93, p = 0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without it. The HALP score could also stratify patients for survival under different pathologic T stages in the subgroup analysis. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.

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 TCRβ. 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.

Cancer-associated inflammation, activation of coagulation cascades, and malnutrition are closely related to the prognosis of patients with malignancy, including renal cell carcinoma (RCC). This study aimed to investigate the prognostic value of a combination of preoperative plasma fibrinogen, prognostic nutritional index, and monocyte-to-lymphocyte ratio (Fib-PNI-MLR) in patients with non-metastatic RCC undergoing nephrectomy. We retrospectively collected medical data from 829 of the 1,019 cases of RCC. The optimal cutoff values of fibrinogen (≥3.54 vs. <3.54, mg/dl), PNI (<47.03 vs. ≥47.03), and MLR (≥0.29 vs. <0.29) were defined using receiver operating characteristic (ROC) analysis and the Fib-PNI-MLR score (range, 0–3) was determined as the sum of points (0 or 1) assigned to each indicator. As a result, Fib-PNI-MLR was an independent risk factor for overall survival (OS), cancer-specific survival (CSS), and metastatic-free survival (MFS) (all P < 0.05). The concordance-index and area under the curve (AUC) were larger for the Fib-PNI-MLR score than that for other clinical parameters. Subgroup analysis (Fuhrman grade G1+G2 and Fuhrman grade G3+G4; pathologic T1, T2, and T3–4 stage) revealed the significant association of a higher Fib-PNI-MLR score with poor urological outcomes (all P < 0.05). Data indicated that patients with higher Fib-PNI-MLR might benefit from partial nephrectomy. The Fib-PNI-MLR score might serve as a promising prognostic factor in patients with non-metastatic RCC.

Background: Both systemic inflammation response and malnutrition are closely related to poor prognosis in patients with certain types of solid tumor. This study investigated the prognostic value of the preoperative combination of systemic immune-inflammation index and prognostic nutritional index (SII-PNI) in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Methods: The predictive ability of SII-PNI was developed and further validated in a cohort of 525 UTUC patients (253 in the training cohort and 272 in the validation cohort) who received RNU. Results: Survival analysis indicated that a SII ≥672.44 was significantly associated with worse overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) while a PNI ≥47.83 was associated with better survival outcomes (All P-values < 0.05). The combination of simultaneously SII ≥672.44 and PNI <47.83 was a powerful independent risk factor for OS, CSS, and RFS (P < 0.05). The SII-PNI had the largest area under the curve (AUC) compared to that for SII or PNI alone and other clinical factors, indicating its superior for predicting survival. In addition, the incorporation of the SII-PNI into established nomograms or current clinical parameters such as pathologic T stage and N stage, achieved higher c-indexes or larger AUC than without, indicating that adding SII-PNI helped predict prognosis. All results were found in the training cohort and confirmed in the validation cohort. Conclusions: SII-PNI was a strong independent predictor of UTUC patients after RNU.

Background: Few studies focused on the relationship between the albumin-to-alkaline phosphatase ratio (AAPR) and the urologic outcomes in patients with non-metastatic renal cell carcinoma (RCC) following curative surgery. The aim of this study was to evaluate the prognostic value of preoperative AAPR in non-metastatic RCC patients. Methods: The prognostic value of AAPR was evaluated in a primary cohort with 419 non-metastatic RCC patients following curative radical or partial nephrectomy and then further validated in an independent cohort consisting of 204 patients. A nomogram was developed based on the independent predictors, and its predictive value was assessed. Results: Kaplan-Meier survival analysis demonstrated that patients with low AAPR levels were significantly associated with worse overall survival (OS) and cancer-specific survival (CSS) compared with patients with high AAPR levels both in two cohorts. Univariate and multivariate analyses revealed that low AAPR was an independent risk factor for OS (HR = 2.745; 95%CI, 1.266-5.953; P = 0.011) and CSS (HR = 3.042; 95%CI, 1.278-7.243; P = 0.012). Moreover, subgroup analysis (Fuhrman grade G1+G2 and Fuhrman grade G3+G4; T1+T2 stage and T3+T4 stage) revealed that low AAPR was also related to worse urological outcomes. Although no significant differences between patients with low AAPR and patients with high AAPR can be observed with regard to CSS under Fuhrman grade G1+G2 (P=0.058) and T1+T2 stage (P=0.318), there was a worse CSS trend in low AAPR patients. The established nomograms for OS and CSS were well calibrated and had moderate discriminative ability (concordance index: 0.821 and 0.839, respectively) Conclusions: Preoperative AAPR might be an independent prognostic factor in patients with non-metastatic RCC. The ratio should be applied in RCC patients for risk stratification and clinical decision-making.

Department of Hematology, The Third Clinical Institute Affiliated to Wenzhou Medical University, People’s Hospital of Wenzhou, Wenzhou, Zhejiang 325006, People’s Republic of China; Department of Respiratory, Rui’an People’s Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325200, People’s Republic of China; Department of Anorectal Surgery, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People‘s Hospital, Lishui, Zhejiang 323000, People’s Republic of China; Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325006, People’s Republic of China; Department of Clinical Pharmacy, Wenzhou People’s Hospital & The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China

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.

Objective: To create multivariable models with readily available clinicopathologic variables for predicting the prognosis of upper tract urothelial carcinomas (UTUC). Patients and methods: We retrospectively analyzed patients diagnosed as UTUC and underwent radical nephroureterectomy in 2 high volumes, tertiary care centers. A total of 445 patients and 227 patients met the inclusion criteria were included for constructing the prediction model and external validation, respectively. Univariable and multivariable Cox regression models were used to analyze independent risk factors, and nomogram and calibration curve were constructed by R project. Results: The median follow-up for the development and external validation cohorts were 33.5 and 32.5 months, respectively. Multivariable analysis detected older age (>= 65 years), with concurrent bladder cancer at diagnosis, with both ureter and renal pelvic tumor, lymphovascular invasion, urothelial carcinoma with divergent differentiation, higher pathological grade and stage, and positive lymph node were significantly associated with poorer outcome of UTUC. The c-index of the nomogram with these above-mentioned independent risk factors to predict the cancer specific survival was 0.74 (95% CI, 0.64-0.84) and 0.73 (95% CI, 0.59-0.87) for the development cohort and external validation cohort, respectively. Conclusions: We developed and externally validated a novel and accurate nomogram with readily available clinicopathological information for predicting the cancer specific survival of UTUC. This nomogram could help clinicians stratify patients with UTUC into different risk groups with distinct prognosis by the total scores obtained from the prediction tool, thus facilitate decision-making and clinical trial designing. (C) 2018 Elsevier Inc. All rights reserved.

This study aimed to evaluate the preoperative prognostic value of systemic inflammation response index and platelet-to-lymphocyte ratio (SIRI-PLR) in patients with upper tract urothelial carcinoma (UTUC). The prognostic ability of SIRI-PLR was evaluated in a training cohort comprising 259 patients with UTUC who underwent radical nephroureterectomy and was further validated in an independent cohort comprising of 274 patients. Multivariate Cox regression models showed that SIRI was significantly associated with overall-survival (OS), cancer-specific survival (CSS), and metastatic-free survival (MFS), and PLR significantly affected OS and CSS (all P < 0.05). In particular, a simultaneously high SIRI-PLR value was considered an independent risk factor even after adjusting for confounding factors and was superior to SIRI alone in predicting survival among patients with UTUC. The analyses of concordance-index and receiver operating characteristic curve showed that incorporation of SIRI-PLR vs. without its incorporation into newly developed nomograms or currently available clinical parameters, such as pathologic T stage, N stage, or tumor grade, had higher accuracy in predicting urologic outcomes of patients with UTUC. These results were observed in the training cohort and were confirmed in the validation cohort. In conclusion, patients with a simultaneously high SIRI-PLR value had significantly poor prognosis. Incorporating SIRI-PLR into currently available clinical parameters can help in patient management.

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.

The present study aimed to investigate the effects of tetrandrine (Tet) on cytocbrome P450 (CY P450) enzymes (CYP1A2, CYP2C9, CYP2D6 and CYP3A4) of rats by using four cocktail probe drugs (phenacetin, tolbutamide, metoprolol, and midazolam). After pretreatment for 14 consecutive days with Tet (treatment group) or saline (control group) by oral administration, probes were given to rats by oral administration. Blood samples were obtained at a series of time-points and the concentrations of four probe drugs in plasma were determined by a UPLC-MS/MS method. The results showed that treatment with Tet had a significant inductive effect on CYP1A2, CYP2C9, CYP2D6, and CYP3A4. Therefore, caution must be needed during the concomitant use of Tet with other drugs metabolized by the corresponding enzymes because of potential drug-Tet interactions. In addition, we found that Tet may be effective in reducing serum uric acid.