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Background: to evaluate the feasibility of texture analysis (TA) based on diffusion kurtosis imaging (DKI) in staging and grading bladder cancer (BC) and to compare it with apparent diffusion coefficient (ADC) and biparametric vesical imaging reporting and data system (VI-RADS). Materials and Methods: In this retrospective study, 101 patients with pathologically confirmed BC underwent MRI with multiple-b values ranging from 0 to 2000 s/mm2. ADC- and DKI-derived parameters, including mean kurtosis (MK) and mean diffusivity (MD), were obtained. First-order texture histogram parameters of MK and MD, including the mean; 5th, 25th, 50th, 75th, and 90th percentiles; inhomogeneity; skewness: kurtosis; and entropy; were extracted. The VI-RADS score was evaluated based on the T2WI and DWI. The Mann–Whitney U-test was used to compare the texture parameters and ADC values between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), as well as between low and high grades. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of each significant parameter and their combinations. Results: The NMIBC and low-grade group had higher MDmean, MD5th, MD25th, MD50th, MD75th, MD90th, and ADC values than those of the MIBC and the high-grade group. The NMIBC and low-grade group yielded lower MKmean, MK25th, MK50th, MK75th, and MK90th than the MIBC and high-grade group. Among all histogram parameters, MD75th and MD90th yielded the highest AUC in differentiating MIBC from NMIBC (both AUCs were 0.87), while the AUC for ADC was 0.86. The MK75th and MK90th had the highest AUC (both 0.79) in differentiating low- from high-grade BC, while ADC had an AUC of 0.68. The AUC (0.92) of the combination of DKI histogram parameters (MD75th, MD90th, and MK90th) with biparametric VI-RADS in staging BC was higher than that of the biparametric VI-RADS (0.89). Conclusions: Texture-analysis-derived DKI is useful in evaluating both the staging and grading of bladder cancer; in addition, the histogram parameters of the DKI (MD75th, MD90th, and MK90th) can provide additional value to VI-RADS.

Hyperoxaluria is a risk factor for urolithiasis and can cause renal epithelial cell injury secondary to oxidative stress. Reactive oxygen species (ROS) produced during cell damage originate from different sources and play different roles. Here, we explored the potential sources of ROS production and investigated the role of ROS from various sources in oxalate-induced oxidative stress and cell injury in normal rat kidney-52 epithelial (NRK-52E) cells. Oxalate-induced injury was assessed by lactate dehydrogenase (LDH) release experiments. 2,7-dichlorodihydrofluorescein diacetate and mitoSOX Red were used to determine the intracellular and mitochondrial ROS (mtROS) production, respectively. The expression level of Nox4, Nox2, and p22 protein was detected by Western blotting to observe the effect of oxalate on nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase (Nox). Furthermore, a specific NADPH oxidase subtype inhibitor and targeted mitochondrial antioxidants were used to preliminarily identify the role of ROS from different sources in renal tubular epithelial cell injury induced by oxalate. We found that oxalate inhibited cell viability, induced LDH release, and prompted intracellular and mitochondrial ROS (mtROS) production. Oxalate also decreased the protein expression level of Nox4 and increased the protein expression level of p22. Mitochondria were also a source of ROS production. In addition, Nox2 inhibitor or mtROS scavenging prevented oxalate-induced cell injury, reversed by an inhibitor of Nox4/1. We concluded that ROS from different sources might play different roles in oxalate-induced renal tubular epithelial cell injury. We also identified new potential targets for preventing or alleviating oxalate-induced renal tubular epithelial cell injury. Graphic abstract

Aims: We aimed to explore the role of nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (Nox4) in the regulation of hypercalciuria-induced renal oxidative damage and crystal depositions...

Bladder cancer is one of the most prevalent cancers. Despite recent advancements in bladder cancer therapy, new strategies are still required for improving patient outcomes, particularly for those who experienced Bacille Calmette–Guerin failure and those with locally advanced or metastatic bladder cancer. Oncolytic viruses are either naturally occurring or purposefully engineered viruses that have the ability to selectively infect and lyse tumor cells while avoiding harming healthy cells. In light of this, oncolytic viruses serve as a novel and promising immunotherapeutic strategy for bladder cancer. A wide diversity of viruses, including adenoviruses, herpes simplex virus, coxsackievirus, Newcastle disease virus, vesicular stomatitis virus, alphavirus, and vaccinia virus, have been studied in many preclinical and clinical studies for their potential as oncolytic agents for bladder cancer. This review aims to provide an overview of the advances in oncolytic viruses for the treatment of bladder cancer and highlights the challenges and research directions for the future.

Introduction: The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety. Methods: We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups. Results: The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, p = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, p < 0.001) and postoperative irrigation (27.6 vs. 92.7%, p < 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, p < 0.001). During the follow-up, no significant difference in the recurrence rate was detected (p = 0.315). Conclusions: TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.

Percutaneous nephrolithotomy (PCNL) has become a routine surgical procedure for treating patients with large kidney stones; the fundamental step in this process is the creation of the nephrostomy tract. In the present study, a meta-analysis was performed to compare the effectiveness and safety of different tract dilation techniques for PCNL. Databases were searched from inception to 1 April 2019 to identify relevant randomized controlled trials. The X-ray exposure time, hemoglobin decrease, stone-free rate, transfusion rate, hospital stay and the complication rate associated with the various techniques were analyzed. A total of 11 studies comprising 1,415 cases were enrolled in the meta-analysis. Significant differences in X-ray exposure time [weighted mean difference (WMD), 30.67; 95% confidence interval (CI), 20.08-41.26; P

BackgroundThe toll-like receptor 4 (TLR4) agonist, Bacille Calmette-Guérin, has exhibited gratifying effects in treating bladder cancer. The study aims to explore the expression pattern, prognostic value, and potential mechanism of TLR4 in bladder cancer.MethodsThe transcriptome file from the GSE13507 dataset in the Gene Expression Omnibus database and the promoter methylation file from the bladder cancer dataset in The Cancer Genome Atlas database were downloaded for analysis. The prognostic value of the TLRs was assessed by univariate Cox regression. Immunohistochemistry was applied to verify the expression of TLR4 in bladder cancer. The drug response is estimated through the R package “pRRophetic.” The CIBERSORT algorithm was carried out to estimate the infiltrating immune cells of samples. Gene Set Enrichment Analysis (GSEA) was performed to identify the pathways involved under varied TLR4 expression levels.ResultsTLR4 is decreased in tumor tissues compared with surrounding tumor tissues or normal tissue, which is also positively correlated to the overall survival rate (hazard ratio [HR] = 0.38) and cancer-specific survival rate (HR = 0.15) of patients with bladder cancer. Low expression of TLR4 is observed in tumors with malignant performance (high pathological grade, higher tumor stage, and progression). Patients with low TLR4 levels are more sensitive to gemcitabine rather than cisplatin. The promoter methylation level of TLR4 is positively associated with TLR4 expression (P < 0.001). The cg14629571 methylation site largely contributes to the overall methylation level. The CIBERSORT analysis shows that high TLR4 expression is associated with lower levels of plasma cells, M0 macrophages, and M1 macrophages. The GSEA results indicate that the TGF-β pathway and apoptosis are activated in high TLR4 bladder cancer, while G2M checkpoint and E2F targets pathways are enriched in low TLR4 bladder cancer.ConclusionThis research discusses the abnormal expression and prognostic value of TLR4 in bladder cancer. The TLR4 expression can effectively predict oncological outcomes and drug sensitivity of bladder cancer patients. TLR4 is also associated with infiltrating immune cell variation and cancer pathway dysregulation. The results provide a novel prognostic marker and potential drug targets for bladder cancer.

International guidelines recommend repeat transurethral resection of bladder tumors (reTURB) for selected patients with high-risk non-muscle invasive bladder cancer to remove possible residual tumors, restage tumors and improve the therapeutic outcome. However, most evidence supporting the benefits of reTURB is from conventional TURB. The role of reTURB in patients receiving initial En bloc resection of bladder tumor (ERBT) is still unknown. PubMed, Embase, Web of Science, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were systematically searched. Finally, this systematic review and meta-analysis included twelve articles, including 539 patients. The rates of residual tumor and tumor upstaging detected by reTURB after ERBT were 5.9% (95%CI, 2.0%–11.1%) and 0.0% (95%CI, 0.0%–0.5%), respectively. Recurrence-free survival, tumor recurrence and progression were comparable between patients with and without reTURB after initial ERBT. The pooled hazard ratios of 1-year, 2-year, 3-year and 5-year recurrence-free survival were 0.74 (95%CI, 0.36–1.51; p = 0.40), 0.76 (95%CI, 0.45–1.26; p = 0.28), 0.83 (95%CI, 0.53–1.32; p = 0.43) and 0.83 (95%CI, 0.56–1.23; p = 0.36), respectively. The pooled relative risks of recurrence and progression were 0.87 (95%CI, 0.64–1.20; p = 0.40) and 1.11 (95%CI, 0.54–2.32; p = 0.77), respectively. Current evidence demonstrates that reTURB after ERBT for bladder cancer can detect relatively low rates of residual tumor and tumor upstaging and appears not to improve either recurrence or progression.

Idiopathic hypercalciuria is an important risk factor for the formation of calcium-containing kidney stones. Matrix metalloproteinase-9 (MMP-9) is closely related to cell and tissue remodeling and is involved in ectopic tissue calcification. However, little is known about its role in kidney stone formation. In this study, we found that the expression of MMP-9 and that of osteoblastic-related proteins was increased in normal rat kidney epithelial-like (NRK-52E) cells following treatment with a high concentration of calcium, while the knockout or overexpression of MMP-9 could, respectively, significantly inhibit or upregulate the expression of osteoblastic-related proteins and calcium crystal deposition. In addition, apoptosis and calcium crystal deposition were significantly reduced in Sprague–Dawley rats with 1,25(OH)2D3-induced hypercalciuria following MMP-9 inhibitor I treatment. Furthermore, inhibiting reactive oxygen species (ROS) production or the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway significantly reduced calcium-induced MMP-9 expression and calcium crystal deposition. In summary, our results suggested that a high calcium concentration promotes epithelial–osteoblastic transformation and calcium crystal deposition in renal tubule cells by regulating the ROS/NF-κB/MMP-9 axis and identified a novel role for MMP-9 in regulating calcium-induced calcium crystal deposition in renal tubules.

Idiopathic hypercalciuria is an important risk factor for the formation of calcium-containing kidney stones. Matrix metalloproteinase-9 (MMP-9) is closely related to cell and tissue remodeling and is involved in ectopic tissue calcification. However, little is known about its role in kidney stone formation. In this study, we found that the expression of MMP-9 and that of osteoblastic-related proteins was increased in normal rat kidney epithelial-like (NRK-52E) cells following treatment with a high concentration of calcium, while the knockout or overexpression of MMP-9 could, respectively, significantly inhibit or upregulate the expression of osteoblastic-related proteins and calcium crystal deposition. In addition, apoptosis and calcium crystal deposition were significantly reduced in Sprague–Dawley rats with 1,25(OH)2D3-induced hypercalciuria following MMP-9 inhibitor I treatment. Furthermore, inhibiting reactive oxygen species (ROS) production or the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway significantly reduced calcium-induced MMP-9 expression and calcium crystal deposition. In summary, our results suggested that a high calcium concentration promotes epithelial–osteoblastic transformation and calcium crystal deposition in renal tubule cells by regulating the ROS/NF-κB/MMP-9 axis and identified a novel role for MMP-9 in regulating calcium-induced calcium crystal deposition in renal tubules.

Background Management of recurrent ureteral stricture is challenging. Consensus on the best surgical choice has not been demonstrated. In this study, we aim to report our experience in treating recurrent ureteral stricture and demonstrate whether robot-assisted procedure for redo ureteral surgery is as effective as open procedure while remaining less invasive. Methods We retrospectively assessed 41 patients (22 robot-assisted surgeries and 19 open surgeries) who underwent consecutive robot-assisted and open procedures for redo ureteral surgery from January 2014 to 2018 in our institution. Perioperative outcomes, including demographics, operative time, estimated blood loss, complications, pain scores, success rate and cost, were compared between two groups. Results There was no significant intergroup difference in terms of age, body mass index, gender composition and American Society of Anesthesiologists scores. A total of 31 patients underwent redo pyeloplasty and ten underwent redo uretero-ureterostomy. Compared with open group, robot-assisted group showed shorter operative time (124.55 min vs. 185.11 min, p < 0.0001), less estimated blood loss (100.00 mL vs. 182.60 mL, p = 0.008) and higher cost (61161.77¥ vs. 39470.79¥, p < 0.0001). Complication rate and pain scores were similar between two groups. Median follow-up periods were 30 and 48 months for robot-assisted and open group respectively. Success rate in the robot-assisted (85.71%) and the open group (82.35%) was not significantly different. Conclusions Robot-assisted surgery for recurrent stricture after previous ureteral reconstruction is as effective as open procedure and is associated with shorter operative time and less estimated blood loss.

To study the impact of body mass index (BMI) on quantitative 24-h urine chemistries in stone forming patients and to explore how overweight and obesity contribute to urolithiasis. A systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science was performed in July 2017 and updated in October 2017 to detect relevant studies. After that, we screened all the relevant articles in accordance with the predetermined inclusion and exclusion criteria. Data of eligible studies were extracted, and then, a meta-analysis was conducted via RevMan 5.3 software. Nine studies, involving 5965 stone forming patients who underwent 24-h urine collection for chemistry analysis, were included in our analysis. BMI was used to clarify the body size. BMI ≥ 25 kg/m2 group, including overweight and obesity patients, erected more calcium (WMD 34.44 mg; 95% CI 11.33–57.55; p = 0.003), oxalate (WMD 3.44 mg; 95% CI 1.40–5.49; p = 0.001), urate (WMD 97.71 mg; 95% CI 63.05–132.38; p

Background Proteins are the most abundant component of kidney stone matrices and their presence may reflect the process of the stone’s formation. Many studies have explored the proteomics of urinary stones and crystals. We sought to comprehensively identify the proteins found in kidney stones and to identify new, reliable biomolecules for use in nephrolithiasis research. Methods We conducted bioinformatics research in November 2020 on the proteomics of urinary stones and crystals. We used the ClusterProfiler R package to transform proteins into their corresponding genes and Ensembl IDs. In each study we located where proteomic results intersected to determine the 20 most frequently identified stone matrix proteins. We used the Human Protein Atlas to obtain the biological information of the 20 proteins and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis to explore their biological functions. We also performed immunohistochemistry to detect the expression of the top five stone matrix proteins in renal tissue. Results We included 19 relevant studies for analysis. We then identified 1,409 proteins in the stone matrix after the duplicates were removed. The 20 most-commonly identified stone matrix proteins were: S100A8, S100A9, uromodulin, albumin, osteopontin, lactotransferrin, vitamin K-dependent protein Z, prothrombin, hemoglobin subunit beta, myeloperoxidase, mannan-binding lectin serine protease 2, lysozyme C, complement C3, serum amyloid P-component, cathepsin G, vitronectin, apolipoprotein A-1, eosinophil cationic protein, fibrinogen alpha chain, and apolipoprotein D. GO and KEGG analysis revealed that these proteins were typically engaged in inflammation and immune response.Immunohistochemistry of the top five stone matrix proteins in renal tissue showed that the expression of S100A8, S100A9, and osteopontin increased, while uromodulin decreased in kidney stone patients. Albumin was rarely expressed in the kidney with no significant difference between healthy controls and kidney stone patients. Conclusion Proteomic analysis revealed some common inflammation-related proteins in the kidney stone matrix. The role of these proteins in stone formation should be explored for their potential use as diagnostic biomarkers and therapeutic targets for urolithiasis.

To compare the image quality of the reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with the full field-of-view (fFOV) DWI in the assessment of bladder cancer (BC); and to explore the possible superiority of bi-planar (axial and sagittal) rFOV DWI over single planar fFOV DWI in predicting muscle-invasiveness of BC.This retrospective study analyzed 61 patients with BC who underwent DWI sequences including axial fFOV DWI, axial rFOV DWI, and sagittal rFOV DWI. Qualitative and quantitative image quality assessment were compared between axial fFOV DWI and rFOV DWI sequences. The tumor with its base could be clearly displayed on DWI was defined as the evaluable lesion, and the number of evaluable lesions detected from single axial fFOV DWI, axial rFOV DWI, sagittal rFOV DWI, and bi-planar rFOV DWI sequences was recorded and compared. The apparent diffusion coefficient (ADC) was compared between non-muscular-invasive bladder cancer (NMIBC) and muscular-invasive bladder cancer (MIBC) based on the sequences of axial fFOV DWI and rFOV DWI, respectively. Vesical Imaging-Reporting and Data System (VI-RADS) was introduced to evaluate the overall risk of muscle-invasiveness of BC and receiver operating characteristic (ROC) curve analysis was applied to assess the diagnostic performance.The contrast-to-noise ratio (CNR) of the rFOV DWI was significantly higher than that of fFOV DWI (p 0.01), while the signal-to-noise ratio (SNR) was significantly lower than that of fFOV DWI (p 0.01). The subjective score of rFOV DWI was significantly higher than that of fFOV DWI (p 0.01). The ADC value of the MIBC group was significantly lower than that of the NMIBC in both rFOV DWI and fFOV DWI (all p 0.01). The number of evaluable lesions detected from the bi-planar rFOV DWI was significantly higher than that detected from the single axial fFOV DWI, axial rFOV DWI, and sagittal rFOV DWI (all p0.01). VI-RADS based on the bi-planar rFOV DWI offered high predictive power (the area under the ROC curve, 0.946) for predicting the presence of muscle-invasiveness of BC.Bi-planar rFOV DWI may provide more diagnostic confidence than the single planar DWI for predicting the presence of muscle-invasiveness in BC, with improved image quality over the fFOV DWI.

The aim of this study is to compare the outcomes of flexible ureteroscopy (fURS) and minimally invasive percutaneous nephrolithotomy (mPNL) for the treatment of renal and/or proximal ureteral stones sized 1-2 cm in the elderly (≥60 years). Between January 2010 and March 2015, 184 consecutive mPNL and fURS were performed to treat intermediate renal and/or proximal ureteral stones in geriatric patients. The records were retrospectively reviewed and outcomes were compared. Although no significant difference was found in the complication rate between two groups, a statistical trend (p = 0.059) in favor of fURS was observed. In addition, multivariate analysis demonstrated that mPNL, preoperative positive urine culture and lower hemoglobin were independent risk factors for postoperative complication (p = 0.016, p = 0.021, p = 0.001, respectively). And fURS was significantly associated with less hemoglobin drop, red blood cell transfusion, analgesics requirement, postoperative hospital duration, and charges of laboratory tests, medical examinations and medications (p = 0.019, p = 0.037, p = 0.006, p = 0.000 and p = 0.007, p = 0.000, p = 0.000, p = 0.001, respectively), while higher costs of operations (p = 0.008). Receiver operating characteristic curve suggested a preoperative hemoglobin of 106.5 g/L as the threshold for predicting red blood cell transfusion after mPNL. The overall one-session stone-free rate of fURS at 1 month was lower (p = 0.006), while it was similar for solitary stone between two groups. Comorbidity and previous stone surgery did not affect postoperative complication and stone-free rate. This study shows that mPNL is more effective for multiple stones, but fURS is associated with potentially less complications and postoperative hospital stay. Furthermore, preoperative hemoglobin level and urine culture can be used to predict postoperative complication risk and they may be helpful in choosing treatment methods for the elderly.

Hyperoxaluria induces oxidative stress, and inflammation causes renal epithelial cell injury in nephrolithiasis, suggesting that reduced oxalate toxicity may be beneficial. This study aimed to investigate whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2, also called Nfe2l2) induced by dimethyl fumarate (DMF) could protect renal epithelial cells against oxalate-mediated injury both in vivo and in vitro. Glyoxylic acid monohydrate was intraperitoneally injected into Sprague-Dawley rats with or without intragastric administration of DMF. We showed that calcium oxalate crystallisation, accompanied by overexpression of oxidant species and inflammatory cytokines and apoptosis in the rat kidney, was partially reversed by treatment with DMF. Furthermore, oxalate induced a reduction in cell viability, cell damage, oxidant species overexpression, mitochondrial dysfunction, and apoptosis in normal rat kidney epithelial-like (NRK-52E) cells, which were reversed by DMF. Pretreatment of NRK-52E cells with DMF significantly increased Nrf2 levels in the nucleus, with subsequent inhibition of the expression of the nicotinamide adenine dinucleotide phosphate subunits Nox4 and P22, canonical inflammation, and osteogenesis-associated differentiation of target genes in the cytoplasm. This effect was partially inhibited by transfection with Nrf2 siRNA and strengthened by transfection with Kelch-like ECH-associated protein 1 siRNA. These results suggest that DMF exerts beneficial effects in nephrolithiasis by inhibiting inflammation and modulating oxidative stress via regulation of Nrf2.

Calcium oxalate (CaOx) is the most common type of urinary stone. Increase of ROS and NADPH oxidase gives rise to inflammation and injury of renal tubular cells, which promotes CaOx stone formation. Recent studies have revealed that the renin-angiotensin system might play a role in kidney crystallization and ROS production. Here, we investigated the involvement of Ang II/AT1R and losartan in CaOx stone formation. NRK-52E cells were incubated with CaOx crystals, and glyoxylic acid-induced hyperoxaluric rats were treated with losartan. Oxidative stress statuses were evaluated by detection of ROS, oxidative products (8-OHdG and MDA), and antioxidant enzymes (SOD and CAT). Expression of NADPH oxidase subunits (Nox2 and Nox4), NF-κB pathway subunits (p50 and p65), and stone-related proteins such as OPN, CD44, and MCP-1 was determined by Western blotting. The results revealed upregulation of Ang II/AT1R by CaOx treatment. CaOx-induced ROS and stone-related protein upregulation were mediated by the Ang II/AT1R signaling pathway. Losartan ameliorated renal tubular cell expression of stone-related proteins and renal crystallization by inhibiting NADPH oxidase and oxidative stress. We conclude that losartan might be a promising preventive and therapeutic candidate for hyperoxaluria nephrolithiasis.

The aim of the present study was to investigate the effect of 1,25(OH)2D3/vitamin D receptor (VDR) and calcium on the expression levels of osteogenic factors in primary renal tubular epithelial cells (RTECs) using genetic hypercalciuric rats. The basal levels of osteogenic factors were detected in Sprague Dawley and genetic hypercalciuric rats. The gene and protein levels of bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2) and osterix were detected in the RTECs transduced with Lenti-VDR-sh and were incubated with calcium. Using the o-cresolphthalein complexone method, the calcium levels of the primary RTECs cultured with Lenti-VDR-sh and with 1,25(OH)2D3 were assessed. The basal levels of BMP2, Runx2 and Osterix in the cells were significantly higher in the genetic hypercalciuric rats compared with the control rats. VDR knockdown in the RTECs reduced the expression levels of BMP2, Runx2 and Osterix. The calcium depositions in the primary RTECs were also decreased following exposure to Lenti-VDR-sh, but increased following treatment with 1,25(OH)2D3. The expression levels of BMP2, Runx2 and Osterix were markedly increased in the cells incubated with calcium compared with the cells treated with normal saline and the untreated cells. These findings indicated that osteogenic factors, including BMP2, Runx2 and Osterix may be important in renal stone formation in idiopathic hypercalciuria. VDR may mediate the increased expression levels of BMP2, Runx2 and Osterix by positively regulating calcium levels in primary RTECs.

Background To update a previously published systematic review and meta-analysis on the efficacy and safety of tubeless percutaneous nephrolithotomy (PCNL). Methods A systematic literature search of EMBASE, PubMed, Web of Science, and the Cochrane Library was performed to confirm relevant studies. The scientific literature was screened in accordance with the predetermined inclusion and exclusion criteria. After quality assessment and data extraction from the eligible studies, a meta-analysis was conducted using Stata SE 12.0. Results Fourteen randomized controlled trials (RCTs) involving 1148 patients were included. Combined results demonstrated that tubeless PCNL was significantly associated with shorter operative time (weighted mean difference [WMD], −3.79 min; 95% confidence interval [CI], −6.73 to −0.85; P = 0.012; I2 = 53.8%), shorter hospital stay (WMD, −1.27 days; 95% CI, −1.65 to −0.90; P

Objective To compare the risk of postoperative ureteral stricture formation following retroperitoneal laparoscopic ureterolithotomy (RPLU) and ureteroscopy with holmium: YAG laser lithotripsy (URSL) in patients with proximal ureteral stones. Materials and Methods We retrospectively reviewed the medical records of patients who underwent RPLU or URSL for proximal ureteral stones between April 2011 and May 2015. Patients were allocated into URSL group or RPLU group and the outcomes were compared. Results A total of 201 patients who underwent 209 procedures including 159 URSL and 50 RPLU with a median follow-up of 30 months were included. No significant difference was observed among the two groups in most baseline parameters, while the stone size was significantly larger in the RPLU group (11.37 ± 2.97 vs 14.04 ± 4.38 mm, p = 0.000). Patients in RPLU group had markedly longer operative time (p = 0.000) and longer postoperative hospital stay (p = 0.000). The initial and one-month stone-free rates were significantly higher in the RPLU group (78.6% vs 100%, p = 0.000 and 82.4% vs 100%, p = 0.001, respectively). Patients in the RPLU had a higher complication rate (18.0% vs 9.4%, p = 0.098) and lower ureteral stricture rate (2.5% vs 2.0%, p = 1.000), while the difference was not significant. Further logistic regression model identified RPLU and female sex as independent risk factors for postoperative complication (Odds Ratio[OR] = 3.57, p = 0.035 and OR = 3.57, p = 0.025, respectively); however, URSL was not an independent risk factor for the formation of postoperative ureteral stricture after adjusting confounding variables (OR = 0.90, p = 0.935). Conclusion RPLU and URSL have similar postoperative ureteral stricture formation risks. RPLU can provide significantly higher stone clearance rate, but relates with more postoperative complications.

As one of the major risks for urolithiasis, hyperoxaluria can be caused by genetic defect or dietary intake. And high oxalate induced renal epithelial cells injury is related to oxidative stress and mitochondrial dysfunction. Here, we investigated whether MitoTEMPO, a mitochondria-targeted antioxidant, could protect against oxalate mediated injury in NRK-52E cells via inhibiting mitochondrial dysfunction and modulating oxidative stress. MitoSOX Red was used to determine mitochondrial ROS (mtROS) production. Mitochondrial membrane potential (Δψm) and quantification of ATP synthesis were measured to evaluate mitochondrial function. The protein expression of Nox4, Nox2, and p22 was also detected to explore the effect of oxalate and MitoTEMPO on NADPH oxidase. Our results revealed that pretreatment with MitoTEMPO significantly inhibited oxalate induced lactate dehydrogenase (LDH) and malondialdehyde (MDA) release and decreased oxalate induced mtROS generation. Further, MitoTEMPO pretreatment restored disruption of Δψm and decreased ATP synthesis mediated by oxalate. In addition, MitoTEMPO altered the protein expression of Nox4 and p22 and decreased the protein expression of IL-6 and osteopontin (OPN) induced by oxalate. We concluded that MitoTEMPO may be a new candidate to protect against oxalate induced kidney injury as well as urolithiasis.

Object To compare the safety and efficacy of rigid ureteroscopic lithotripsy (rigid URSL) and percutaneous nephrolithotomy (PCNL) in treating large proximal ureteral stones. Methods A systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science databases was performed to find out relevant studies. After literature screening according to the predetermined inclusion and exclusion criteria, data of eligible studies was extracted and then a meta-analysis was conducted via RevMan 5.3 software. Results Five randomized controlled trials (RCTs), one prospective and four retrospective cohort studies involving 837 patients were included. Patients underwent rigid URSL were associated with shorter operation time (WMD, -23.66min; 95%CI, −45.00 to -2.32; p = 0.03), shorter hospital stay (WMD, -2.76d; 95%CI, −3.51 to −2.02; p< 0.00001), lower 3rd-day (RR, 0.73; 95%CI, 0.66 to 0.82; p < 0.00001) and 1st-month (RR, 0.82; 95%CI, 0.77 to 0.87; p < 0.00001) stone-free rate, higher risk of conversion to other surgical procedures (RR, 4.28; 95%CI, 1.93 to 9.46; p = 0.0003), higher incidence of migration (RR, 28.49; 95%CI, 9.12 to 89.00; p < 0.00001) and ureteral perforation (RR, 6.06; 95%CI, 1.80 to 20.44; p = 0.004), lower risk of fever (RR, 0.64; 95%CI, 0.42 to 0.97; p = 0.04), transfusion (RR, 0.19; 95%CI, 0.04 to 0.85; p = 0.03) and hematuria (RR, 0.38; 95%CI, 0.25 to 0.57; p < 0.0001). No significant difference was observed in terms of incidence of embolization, pain and ureterostenosis. When cohort studies or studies in which flexible ureteroscopy was used as an intraoperative auxiliary procedure were excluded, we both found that most of the results kept stable. Conclusions Both PCNL and rigid URSL are safe for patients with large proximal ureteral stones while PCNL is more effective in stone clearance.

The objective of this research was to measure the effects of energising drinks containing caffeine and glucose, upon mental activity during sustained selective attention. Non-invasive electrophysiological brain recordings were made during a behavioural study of selective attention in which participants received either energising or placebo drinks. We tested specifically whether energising drinks have significant effects upon behavioural measures of performance during a task requiring sustained visual selective attention, as well as on accompanying components of the event-related potential (ERPs) related to information processing in the brain. Forty healthy volunteers were blindly assigned to receive either the energising drink or a similar-tasting placebo drink. The behavioural task involved identifying predefined target stimulus among rapidly presented streams of peripheral visual stimuli, and making speeded motor responses to this stimulus. During task performance, accuracy, reaction times and ongoing brain activity were stored for analysis. The energising drink enhanced behavioural performance both in terms of accuracy and speed of reactions. The energising drink also had significant effects upon the event-related potentials. Effects started from the enhancement of the earliest components (Cl/P1), reflecting early visual cortical processing in the energising-drink group relative to the placebo group over the contralateral scalp. The later N1, N2 and P3 components related to decision-making and responses were also modulated by the energising drink. Energising drinks containing caffeine and glucose can enhance behavioural performance during demanding tasks requiring selective attention. The behavioural benefits are coupled to direct effects upon neural information processing.

Purpose To clarify the outcome of flexible ureteroscopy (fURS) for management of renal calculi without preoperative stenting. Methods A total of 171 patients who received 176 fURS procedures for unilateral renal stones were reviewed. All procedures were divided into two groups depending on whether they received ureteral stenting preoperatively. Baseline characteristics of patients, stone burden, operation time, stone-free rates, and complications were compared between both groups. Results Successful primary access to the renal pelvis was achieved in 104 of 114 (91.2%) patients without preoperative stenting, while all procedures with preoperative stenting (n = 62) were successfully performed. A total of 156 procedures were included for further data analysis (56 procedures in stenting group and 100 in non-stenting group). No significant differences was found regardless of a preoperative stent placement in terms of stone-free rate (73.2% with stenting vs. 71.0% without, P = 0.854), operative time (70.4 ± 32.8 with stenting vs. 70.2 ± 32.1 without, P = 0.969). Conclusions fURS for management of renal stone without preoperative ureteral stenting are associated with well outcome in short term follow-up. Our study may help patients and doctors to decide if an optional stent is placed or not.

Background.MicroRNAs (miRNAs) influence a variety of biological functions by regulating gene expression post-transcriptionally. Aberrant miRNA expression has been associated with many human diseases. Urolithiasis is a common disease, and idiopathic hypercalciuria (IH) is an important risk factor for calcium urolithiasis. However, miRNA expression patterns and their biological functions in urolithiasis remain unknown.Methods and Results.A multi-step approach combining microarray miRNA and mRNA expression profile and bioinformatics analysis was adopted to analyze dysregulated miRNAs and genes in genetic hypercalciuric stone-forming (GHS) rat kidneys, using normal Sprague-Dawley (SD) rats as controls. We identified 2418 mRNAs and 19 miRNAs as significantly differentially expressed, over 700 gene ontology (GO) terms and 83 KEGG pathways that were significantly enriched in GHS rats. In addition, we constructed an miRNA-gene network that suggested that rno-miR-674-5p, rno-miR-672-5p, rno-miR-138-5p and rno-miR-21-3p may play important roles in the regulatory network. Furthermore, signal-net analysis suggested that NF-kappa B likely plays a crucial role in hypercalciuria urolithiasis.Conclusions.This study presents a global view of mRNA and miRNA expression in GHS rat kidneys, and suggests that miRNAs may be important in the regulation of hypercalciuria. The data provide valuable insights for future research, which should aim at validating the role of the genes featured here in the pathophysiology of hypercalciuria.

Previous research has identified a number of factors that appear to moderate the behavioural response to glucose administration. These include physiological state, dose, types of cognitive tasks used and level of cognitive demand. Another potential moderating factor is the length of the fasting interval prior to a glucose load. Therefore, we aimed to examine the effect of glucose dose and fasting interval on mood and cognitive function. The current study utilised a double-blind, placebo-controlled, balanced, six period crossover design to examine potential interactions between length of fasting interval (2 versus 12 hours) and optimal dose for cognition enhancement. Results demonstrated that the higher dose (60 g) increased working memory performance following an overnight fast, whereas the lower dose (25 g) enhanced working memory performance following a 2-h fast. The data suggest that optimal glucose dosage may differ under different conditions of depleted blood glucose resources. In addition, glucoregulation was observed to be a moderating factor. However, further research is needed to develop a model of the moderating and mediating factors under which glucose facilitation is best achieved.

Acute stress has been associated with changes in cognitive performance and mood, and these have been in part associated with stress-related increased release of cortisol. Both glucose and caffeine consumed in isolation have been shown to moderate cortisol response and affect cognitive performance and affect mood; however, there has been very little research into their behavioural and physiological effects when taken in combination. The aim of this study was to assess the effect of the two substances in combinationunder stressful and physically demanding conditions (fire-fighting training) on cognition, mood and cortisol release. Using a double-blind, mixed measures design, 81 participants were administered a 330-ml drink containing either (1) 50 g glucose and 40 mg caffeine, (2) 10.25 g of fructose/glucose and 80 mg caffeine or a placebo drink and tested across a range of cognitive tasks, mood and physiological measures. The results showed an increase in grip strength and improved memory performance after ingestion of the drink containing 50 g glucose and 40 mg caffeine, and both active drinks resulted in improved performance on the information-processing task compared to the placebo. In terms of mood effects, the drink containing 50 g glucose and 40 mg caffeine led to a reduction in anxiety and significantly reduced self-reported levels of stress following the fire-fighter training. Based on the results of this study, in situations of stress combined with physical performance, administration of an energy drink containing glucose and caffeine might be an easy to implement and cost effective way to maintain mental performance levels and to ameliorate the negative effects of stress on mood.

Objective To address whether matrix Gla protein (MGP) can inhibit mineralization in normal rat kidney tubular cells (NRK-52E) under high concentration of calcium. Materials and Methods NRK-52E cells were treated with high concentration of calcium. The viability and apoptosis of cells were detected by cell counting kit-8 and flow cytology, respectively. Real-time-polymerase chain, Western blotting, and immunofluorescence analysis were conducted to detect the expression of MGP. Cells were transfected with plasmid-MGP or siRNA-MGP for up- or down-regulation of the expression of MGP, respectively. Rat recombinant MGP was also used as supplementation of exogenous MGP. Alizarin red staining was conducted to detect the adherent and deposition of calcium salt. Results High concentration of calcium suppressed MGP expression in NRK-52E cells. There was significant mineralization when NRK-52E cells were treated with high concentration of calcium. Supplementation with exogenous rat recombinant MGP and overexpression of endogenous MGP both decreased the adherent and deposition of calcium salt to NRK-52E cells, while silence of MGP showed reverse results. Conclusion MGP plays an inhibitory role in the stone formation. However, high concentration of calcium significantly inhibits the expression of MGP and then promotes mineralization in NRK-52E cells.

Objective To evaluate the feasibility and efficacy of intraoperative ultrasonography in laparoscopic partial nephrectomy (LPN) for intrarenal tumors. Patients and methods All patients who underwent LPN for renal tumors in our institution from January 2010 to October 2016 were assessed retrospectively. Patients were divided into two groups, the first with totally intrarenal tumors (TIT group), defined as a solid renal mass with no exophytic element on both preoperative and intraoperative evaluations, and the second with exophytic tumors (control group). General information and perioperative data of the two groups were compared, including tumor characteristics, operative time, estimated blood loss, warm ischemia time and pathological findings. Intraoperative laparoscopic ultrasonography (ILUS) was used to precisely locate and delineate the TIT border, as well as seeking for other suspected lesions. Results We identified 583 patients who underwent LPN in our center, including 46 in the TIT and 537 in the control group. All patients in the TIT group were evaluated by ILUS, and all TIT procedures were successfully performed with only one conversion to open surgery. The mean tumor sizes in the TIT and control groups were 2.42 ± 0.46 cm and 3.29 ± 1.43 cm (p < 0.001), respectively. The TIT group’s R.E.N.A.L. nephrometry score was higher than that of the control group (median 8.5 vs 6.0, p < 0.001), and their mean operation times were 127.2 ± 16.0 min and 120.1 ± 19.2 min, respectively. Mean estimated blood loss was higher in the TIT than in the control group (161.3 ml vs 136.6 ml, p = 0.003). Mean warm ischemia time differed in the TIT and control groups (22.2 ± 6.4 vs 20.6 ± 4.7 min, p = 0.105), but not significantly. Rates of open conversion and positive margins, as well as rates of major postoperative complications, pathological findings, and 1-month changes in renal function, were similar in the two groups. Conclusion Intraoperative ultrasonography is technically feasible in patients undergoing LPN for TITs. This method may reduce the need for radical nephrectomy in patients with endogenic renal masses.

Many studies compared the serum/plasma 1,25 dihydroxyvitamin D3 (1,25(OH)2D) and 25 hydroxyvitamin D3 (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs), calcium SFs had significantly higher concentrations of 1,25(OH)2D (weighted mean difference (WMD), 10.19 pg/mL; 95% confidence interval (CI), 4.31–16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07–18.50; p = 0.002, respectively) than non-stone formers, while the levels of 25(OH)D (WMD, 0.88 ng/mL; 95% CI, −1.04–2.80; p = 0.37 and WMD, −0.63 ng/mL; 95% CI, −2.72–1.47; p = 0.56, respectively) are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH)2D (WMD, 9.41 pg/mL; 95% CI, 0.15–18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, −0.20–5.69; p = 0.07, respectively) and markedly higher 25(OH)D (WMD, 5.02 ng/mL; 95% CI, 0.99–9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14–7.90; p = 0.0006, respectively). Normocalciuria SFs had elevated 1,25(OH)2D level (WMD, 6.85 pg/mL; 95% CI, −5.00–18.71; p = 0.26) and comparable 25(OH)D (WMD, 0.94 ng/mL; 95% CI, −3.55–5.43; p = 0.68). Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH)2D is associated with urinary stones and a higher level of circulating 25(OH)D is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones.