One-stage efficacy of single tract minimally invasive ECIRS in the improved prone frog split-leg position for staghorn stones.

OBJECTIVE: To explore the feasibility, safety, and effectiveness of single tract minimally invasive endoscopic combined intrarenal surgery (stmECIRS) in the improved prone frog split-leg position for staghorn stones. METHOD: A total of 83 patients with staghorn stones were retrospectively reviewed between January 2018 and June 2021. According to surgical procedure and position, patients were divided into a group of single tract minimally invasive percutaneous nephroscopy (stmPNL) in the prone position and a group of stmECIRS in the improved prone frog split-leg position (turned to the prone position after preset the flexible ureteroscope sheath in lithotomy position, meanwhile, bend both hips and knees to be frog abduction). Demographic characteristics, laboratory tests, stone characters, surgical information, stone-free rate (SFR), and perioperative complications were observed and analyzed. RESULTS: There were no significant differences in demographic characteristics, changes level of Scr and Hb, stone size, radiation density, length of hospital stay, and operation time between the two groups. One-stage SFR in the stmECIRS group was significantly higher than that in the stmPNL group (84.4% vs. 57.9%) (P = 0.007), only 2 patients required blood transfusion after surgery (P = 0.862), and other postoperative complications were not statistically significant (P = 0.345). CONCLUSIONS: StmECIRS in improved prone frog split-leg position has a higher one-stage SFR than stmPNL for staghorn renal stones, and without complications increased, which is a safe, efficient and feasible treatment.

Erratum: Nodal Promotes the Migration and Invasion of Bladder Cancer Cells via Regulation of Snail: Erratum.

[This corrects the article DOI: 10.7150/jca.29205.].

Trim24 prompts tumor progression via inducing EMT in renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor originating from renal tubular epithelial cells with poor prognosis and high metastatic rate. Tripartite motif-containing 24 (Trim24) is a member of the tripartite motif (Trim) family and also a valuable oncogene, but its role in RCC remains unclear. We constructed the overexpression and knockdown of Trim24 cell lines to investigate its roles in RCC progression. CCK8, wound healing, and transwell assay were performed to determine the proliferation, migration, and invasion of RCC cell lines, respectively. Moreover, the expression of Trim24 and its clinicopathological significance were evaluated in a human RCC tissue microarray. From our results, Trim24 promoted the proliferation, migration, and invasion of RCC cells in vitro. Importantly, overexpression of Trim24 led to a significant increase in the expression levels of MMP-2, MMP-9, fibronectin, snail, vimentin, N-cadherin, and ß-catenin, inducing the EMT process in turn, while the expression of these proteins was significantly downregulated when Trim24 was knocked down in ACHN cells. In addition, Trim24 was significantly upregulated in RCC, and its high expression was negatively associated with the tumor size. Trim24 might operate as an oncogene in RCC progression by inducing the EMT process, suggesting that Trim24 was a potential target for human RCC.

Risk factors of infectious complications after retrograde intrarenal surgery: a retrospective clinical analysis.

OBJECTIVE: Stone disease is one of the most common afflictions in modern society. Complications following retrograde intrarenal surgery (RIRS) vary considerably, and small-diameter ureteral access sheaths are reportedly significantly associated with rates of infectious complications following RIRS. This study aimed to explore additional risk factors for infectious complications after RIRS. METHODS: This study retrospectively analyzed 602 patients who underwent RIRS between December 2016 and October 2019 at the First Affiliated Hospital of Fujian Medical University. All flexible ureteroscopic lithotripsy processes were conducted with patients under general anesthesia in the low lithotomy position. Postoperative systemic inflammatory response syndrome (SIRS) was diagnosed; statistical analyses comprised two-way analysis of variance (ANOVA) and one-way multivariate ANOVA. RESULTS: The incidence of infectious complications after RIRS was 7.14%. Operative time was an independent risk factor that increased the risk of infection. Stone size >2 cm was observed in 153 (27.37%) patients in the SIRS group and 29 patients (67.44%) in the non-SIRS group. CONCLUSIONS: Findings in the literature suggest that early antibiotic treatment and active fluid therapy might lower the rate of infectious complications after RIRS. Our results indicate that extended operative time and increased stone size may be risk factors for infectious complications after RIRS.

Management of large renal stones with super-mini percutaneous nephrolithotomy: an international multicentre comparative study.

OBJECTIVES: To comparatively evaluate the clinical outcomes of super-mini percutaneous nephrolithotomy (SMP) and mini-percutaneous nephrolithotomy (Miniperc) for treating urinary tract calculi of >2 cm. PATIENTS AND METHODS: An international multicentre, retrospective cohort study was conducted at 20 tertiary care hospitals across five countries (China, the Philippines, Qatar, UK, and Kuwait) between April 2016 and May 2019. SMP and Miniperc were performed in 3525 patients with renal calculi with diameters of >2 cm. The primary endpoint was the stone-free rate (SFR). The secondary outcomes included: blood loss, operating time, postoperative pain scores, auxiliary procedures, complications, tubeless rate, and hospital stay. Propensity score matching analysis was used to balance the selection bias between the two groups. RESULTS: In all, 2012 and 1513 patients underwent SMP and Miniperc, respectively. After matching, 1380 patients from each group were included for further analysis. Overall, there was no significant difference in the mean operating time or SFR between the two groups. However, the hospital stay and postoperative pain score were significantly in favour of SMP (both P < 0.001). The tubeless rate was significantly higher in the SMP group (72.6% vs 57.8%, P < 0.001). Postoperative fever was much more common in the Miniperc group (12.0% vs 8.4%, P = 0.002). When the patients were further classified into three subgroups based on stones diameters (2-3, 3-4, and >4 cm). The advantages of SMP were most obvious in the 2-3 cm stone group and diminished as the size of the stone increased, with longer operating time in the latter two subgroups. Compared with Miniperc, the SFR of SMP was comparable for 3-4 cm stones, but lower for >4 cm stones. There was no statistical difference in blood transfusions and renal embolisations between the two groups. CONCLUSIONS: Our data showed that SMP is an ideal treatment option for stones of <4 cm and is more efficacious for stones of 2-3 cm, with lesser postoperative fever, blood loss, and pain compared to Miniperc. SMP was less effective for stones of >4 cm, with a prolonged operating time.

SNHG16 regulates invasion and migration of bladder cancer through induction of epithelial-to-mesenchymal transition.

Bladder cancer (BCa) is one of the most common urinary malignancies in the world. Growing evidence suggests that epithelial-to-mesenchymal transition (EMT) is a major contributor for BCa metastasis. lncRNA small nucleolar RNA host gene 16 (SNHG16) has been reported as a tumor promoter in many cancers. This study aims to investigate the function and mechanism of SNHG16 on EMT in BCa. Quantitative RT-PCR (qRT-PCR) was used to determine the expression of SNHG16 in human BCa tissues and TGF-ß-induced cells. Western blot (WB) was performed to evaluate the expression of EMT-related proteins. Transwell assay was exerted to assess the migration and invasion ability of SNHG16 in BCa. RNA pull-down assay was conducted to confirm the RNA-RNA interaction. The precise mechanism by which SNHG16 regulated EMT process in BCa was also explored. SNHG16 was found up-regulated in TGF-ß-induced BCa cells and BCa tissues. Transwell assay showed that overexpression of SNHG16 significantly promoted the migration and invasion of BCa cells, whereas knock-down of SNHG16 caused the opposite effects. Then, the interaction between SNHG16 and miR-200a-3p was verified by dual-luciferase reporter assay and RNA pull-down assay. And the effects of knock-down or overexpression of SNHG16 on migration and invasion were reversed by co-transfecting miR-200a-3p inhibitors or mimics. This study first demonstrated that SNHG16 was responsible for EMT of BCa cells via miR-200a-3p/ ZEB1/ZEB2 axis. These results provided a potential therapeutic strategy for BCa treatment, especially in metastatic BCa.

[Application of serum amino acid profile in urolithiasis based on gas chromatography-mass spectrometry].

An overall workflow based on gas chromatography-mass spectrometry (GC-MS) was established for the analysis of the serum amino acid profile between urolithiasis patients (n=80, age (46.82±13.39) years) and healthy controls (n=37, age (43.46±12.79) years). The raw data from GC-MS analysis were processed by multivariate statistical methods to build the model. Following this, student's t-test and logistic regression were performed and receiver operator characteristic (ROC) curve was plotted to identify the potential biomarkers. Good linearities were observed for the target amino acids, with correlation coefficients (R2) greater than 0.9985. The limits of detection (LODs) were 0.1-4.0 µmol/L. The results indicated a significant discrimination between the urolithiasis and control groups. Five significantly differentially expressed amino acids (variable importance in projection (VIP)>1 and p<0.05) were found to provide the scientific evidence for the early diagnosis of urolithiasis, while the sensitivity of the integrated five differential amino acids was up to 97.3%. In particular, the area under the curve (AUC) of serine reached 0.819, which suggested a great clinical screening value.

Nodal Promotes the Migration and Invasion of Bladder Cancer Cells via Regulation of Snail.

Urinary bladder cancer is one of commonly diagnosed malignancies worldwide, especially in males. Understanding the mechanisms of advanced metastasis in bladder cell is important for therapy and drug development. Nodal, an important embryonic morphogen, has been reported to modulate tumorigenesis. We found that the expression of Nodal was upregulated in bladder cancer cells and tissues as compared to their corresponding controls. Knockdown of Nodal can suppress the migration, invasion, and epithelial-to-mesenchymal transition (EMT) of bladder cancer cells. Nodal can positively regulate the expression of Snail, one powerful EMT transcription factors, in bladder cancer cells. Overexpression of Snail can attenuate the si-Nodal suppressed cell migration and invasion. Nodal can increase the transcription and protein stability of Snail in bladder cancer cells. YY1, which can be activated by Nodal, is responsible for Nodal induced transcription of Snail. ATM, which can stabilize Snail by phosphorylation on Serine-100, was involved in Nodal upregulated protein stability of Snail. Collectively, our data showed that Nodal can trigger the malignancy of bladder cancer cells via increasing the transcription and protein stability of Snail. It indicated that Nodal might be a potential therapeutic target for bladder cancer treatment.

The role of TSG-6 and uroplakin III in bladder pain syndrome/ interstitial cystitis in rats and humans.

OBJECTIVES: We investigated the relationship between the expression of tumor necrosis factor-inducible gene 6 (TSG-6) with inflammation and integrity of the bladder epithelium in the bladder tissues of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and the mechanism of action using a rat model of BPS/IC. MATERIALS AND METHODS: Expression of TSG-6 and uroplakin III was determined by immuno- histochemistry of bladder biopsy samples from control human subjects and patients with verified BPS/IC. Our rat model of BPS/IC was employed to measure the perfusion of bladders with hyaluronidase, and assessment of the effect of TSG-6 administration on disease progression. Treatment effects were assessed by measurement of metabolic characteristics, RT-PCR of TGR-6 and interleukin-6, bladder histomorphology, and immunohistochemistry of TGR-6 and uroplakin III. RESULTS: The bladders of patients with BPS/IC had lower expression of uroplakin III and higher expression of TSG-6 than controls. Rats treated with hyaluronidase for 1 week developed the typical signs and symptoms of BPS/IC, and rats treated with hyaluronidase for 4 weeks had more serious disease. Administration of TSG-6 reversed the effects of hyaluronidase and protected against disease progression. CONCLUSION: Our results indicate that TSG-6 plays an important role in maintaining the integrity of the bladder epithelial barrier.

Intercellular transfer of P-glycoprotein from the drug resistant human bladder cancer cell line BIU-87 does not require cell-to-cell contact.

PURPOSE: The efflux activity of transmembrane P-glycoprotein prevents various therapeutic drugs from reaching lethal concentrations in cancer cells, resulting in multidrug resistance. We investigated whether drug resistant bladder cancer cells could transfer functional P-glycoprotein to sensitive parental cells. MATERIALS AND METHODS: Drug sensitive BIU-87 bladder cancer cells were co-cultured for 48 hours with BIU-87/ADM, a doxorubicin resistant derivative of the same cell line, in a Transwell® system that prevented cell-to-cell contact. The presence of P-glycoprotein in recipient cell membranes was established using fluorescein isothiocyanate, laser scanning confocal microscopy and Western blot. P-glycoprotein mRNA levels were compared between cell types. Rhodamine 123 efflux assay was done to confirm that P-glycoprotein was biologically active. RESULTS: The amount of P-glycoprotein protein in BIU-87 cells co-cultured with BIU-87/ADM was significantly higher than in BIU-87 cells (0.44 vs 0.25) and BIU-87/H33342 cells (0.44 vs 0.26, each p <0.001), indicating P-glycoprotein transfer. P-glycoprotein mRNA expression was significantly higher in BIU-87/ADM cells than in co-cultured BIU-87 cells (1.28 vs 0.30), BIU-87/H33342 (0.28) and BIU-87 cells (0.25, each p <0.001), ruling out a genetic mechanism. After 30 minutes of efflux, rhodamine 123 fluorescence intensity was significantly lower in BIU-87/ADM cells (5.55 vs 51.45, p = 0.004) and co-cultured BIU-87 cells than in BIU-87 cells (14.22 vs 51.45, p <0.001), indicating that P-glycoprotein was functional. CONCLUSIONS: Bladder cancer cells can acquire functional P-glycoprotein through a nongenetic mechanism that does not require direct cell contact. This mechanism is consistent with a microparticle mediated process.

Intravesical hyaluronic acid and alkalinized lidocaine for the treatment of severe painful bladder syndrome/interstitial cystitis.

INTRODUCTION AND HYPOTHESIS: Intravesical instillation of hyaluronic acid (HA) may restore the integrity of glycosaminoglycan layer in patients with painful bladder syndrome/interstitial cystitis (PBS/IC), and the benefit may be improved with addition of alkalinized lidocaine (AL). METHODS: 48 women with severe PBS/IC who failed oral medications were enrolled and divided into one trial and two control groups. The trial group received intravesical 40 mg HA, 10 ml of 2 % lidocaine and 5 ml of 8.4 % sodium bicarbonate on a weekly basis for 8 weeks and then monthly for 4 months with a subsequent follow-up of 24 weeks, while the two control groups received 40 mg HA and mixture of 10 ml of 2 % lidocaine and 5 ml of 8.4%sodium bicarbonate respectively following the same procedure. Response to therapy was evaluated by Global Response Assessment, voids per day, Visual Analogue Scale for pain, frequency and urgency, O'leary-Sant Interstitial Cystitis Symptom Index and Problem Index, cystoscopy and bladder capacity. RESULTS: Overall 45 patients finished this study protocol. The HA + AL group and the AL group showed significant improvement at week 2 (P < 0.01), while the HA group began to show effect at week 4 (P < 0.01). There was no improvement in the AL group at week 24 and these patients quitted the study without follow up. Contrarily, the HA + AL and HA group kept on improving till the end of the study without significant difference between the two groups. CONCLUSIONS: Intravesical instillation of HA and AL may provide both immediate and sustained relief of symptoms in severe PBS/IC in this preliminary study.