N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation.

Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress.

Alkaline phosphatase combines with CT factors for differentiating small (≤ 4 cm) fat-poor angiomyolipoma from renal cell carcinoma: a multiple quantitative tool.

PURPOSE: This study aimed to evaluate the diagnostic value of serum and CT factors to establish a convenient diagnostic method for differentiating small (≤ 4 cm) fat-poor angiomyolipoma (AML) from renal cell carcinoma (RCC). MATERIALS AND METHODS: This study analyzed the preoperative serum laboratory data and CT data of 32 fat-poor AML patients and 133 RCC patients. The CT attenuation value of tumor (AVT), relative enhancement ratio (RER), and heterogeneous degree of tumor were detected using region of interest on precontrast phase (PCP) and the corticomedullary phase. Multivariate regression was performed to filter the main factors. The main factors were selected to establish the prediction models. The area under the curve (AUC) was measured to evaluate the diagnostic efficacy. RESULTS: Fat-poor AML was more common found in younger (47.91 ± 2.09 years vs 53.63 ± 1.17 years, P = 0.02) and female (70.68 vs 28.13%, P < 0.001) patients. Alkaline phosphatase (ALP) was higher in RCC patients (81.80 ± 1.75 vs 63.25 ± 2.95 U/L, P < 0.01). For CT factors, fat-poor AML was higher in PCP_AVT (40.30 ± 1.49 vs 32.98 ± 0.69Hu, P < 0.01) but lower in RER (67.17 ± 3.17 vs 84.64 ± 2.73, P < 0.01). Gender, ALP, PCP_AVT and RER was found valuable for the differentiation. When compared with laboratory-based or CT-based diagnostic models, the combination model integrating gender, ALP, PCP_AVT and RER shows the best diagnostic performance (AUC = 0.922). CONCLUSION: ALP was found higher in RCC patients. Female patients with ALP < 70.50U/L, PCP_AVT > 35.97Hu and RER < 82.66 are more likely to be diagnose as fat-poor AML.

[Corrigendum] miR­195 inhibits cell proliferation and angiogenesis in human prostate cancer by downregulating PRR11 expression.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that a pair of data panels featured in Figs. 1B and 4C contained overlapping sections, such that data that were intended to show the results from differently performed experiments appeared to have been derived from the same original source (specifically, the 'LNCaP / miR­NC' panel in Fig. 1B and the 'LNCaP / miR­195+ PRR11' panel in Fig. 4C were overlapping). The authors were able to re­examine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 1, containing the correct data for Fig. 1B (wherein the error was contained), is shown on the next page. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 39: 1658­1670, 2018; DOI: 10.3892/or.2018.6240].

Myocardin Reverses Hypoxia-Inducible Factor-1α Mediated Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in Hypoxia Induced by Cobalt Chloride.

PURPOSE: We aimed to investigate the mechanism of phenotypic transformation of corporal cavernosum smooth muscle cells (CCSMCs) under hypoxic conditions in vitro. MATERIALS AND METHODS: In this study, a hypoxia model was established using cobalt chloride (CoCl2). CCSMCs were treated with different concentrations of CoCl2 for varying time periods, and cell viability was assessed. Hypoxia-inducible factor-1α (HIF-1α), myocardin (Myocd) and phenotypic markers were detected in the CCSMCs. We also transfected the CCSMCs with si-HIF-1α and Ad-Myocd and evaluated the effects on phenotypic modulation of CCSMCs and the relationship between HIF-1α and Myocd was evaluated. RESULTS: CoCl2 inhibited the viability of CCSMCs in a dose- and time-dependent manner, and treatment with 300 µM CoCl2 for 48 hours were the optimal conditions for establishing the hypoxia model. The results showed increased expression levels of HIF-1α and osteopontin and decreased Myocd, alpha-smooth muscle actin, and calponin levels in CCSMCs under hypoxia. HIF-1α knockdown reversed hypoxia-induced phenotypic transformation with elevated Myocd expression. Overexpression of Myocd also reversed the effect of hypoxia on the phenotypic switch, but did not affect HIF-1α expression. CONCLUSIONS: Our findings showed that HIF-1α was involved in the effect of hypoxia induced by CoCl2 on CCSMC phenotypic modulation, and Myocd overexpression could inhibit this process. Thus, Myocd might be a potential therapeutic target for erectile dysfunction under hypoxia or HIF-1α activation.

NLRP3 downregulation enhances engraftment and functionality of adipose-derived stem cells to alleviate erectile dysfunction in diabetic rats.

Background: The transplantation of adipose-derived stem cells (ASCs) is a most promising treatment for diabetic erectile dysfunction (DMED). However, the effect of high glucose on the post-transplantation survival of stem cells limits the efficacy of ASCs transplantation. Prolonging the survival time of ASCs in vivo after transplantation is a key issue in the utilization of ASCs for DMED. Herein, we aimed to investigate the therapeutic effect of ASCs by downregulating NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) as well as its mechanism of action in DMED. Methods: ASCs were obtained by isolating subcutaneous fat from SD rats and were identified using lipogenic and osteogenic differentiation assays, as well as flow cytometric analysis. The shNLRP3 lentivirus with the best downregulating effect was screened, and shNLRP3 lentivirus (LV-shNLRP3) was transfected into ASCs (ASCsshNLRP3) to detect apoptosis and the reactive oxygen species (ROS) levels in each group under high glucose conditions. In DMED rats, ASCsLV-shNLRP3, ASCsLV-control, or phosphate buffered saline (PBS) were administrated via intra-cavernous injection, and normal rats served as normal controls. One week post-injection, animal imaging was performed to track the ASCs. Four weeks post-injection, erectile function was evaluated by measuring the intra-cavernosal pressure and mean arterial pressure. Corpus cavernosum pyroptosis and endothelial function were examined by western blotting and immunofluorescence. Results: NLRP3-mediated pyroptosis might be a pathogenic mechanism of ED and DMED. ASCs were isolated successfully. Thereafter, the LV-shNLRP3 with the highest transfection efficiency was selected and used to modify ASCs successfully. LV-shNLRP3 could protect ASCs paracrine function under hyperglycemia through anti-apoptosis and anti-ROS deposition mechanisms. Furthermore, ASCsLV-shNLRP3 showed an advantage in the suppression of pyroptosis compared to ASCsLV-control. The ASCsLV-shNLRP3 group had improved cavernous endothelial function and smooth muscle injury, thus reversing erectile function, and was superior to the ASCsLV-control group. Conclusions: NLRP3 Inflammasome-mediated pyroptosis might be involved in DMED formation. Intra-cavernous injection of ASCsLV-shNLRP3 could suppress cavernosal pyroptosis, contributing to improved erectile function in DMED rats.

Screening and identification of NOTCH1, CDKN2A, and NOS3 as differentially expressed autophagy-related genes in erectile dysfunction.

BACKGROUND: Loss of function of key autophagy genes are associated with a variety of diseases. However specific role of autophagy-related genes in erectile dysfunction ED remains unclear. This study explores the autophagy-related differentially expressed genes (ARGs) profiles and related molecular mechanisms in Corpus Cavernosum endothelial dysfunction, which is a leading cause of ED. METHODS: The Gene Expression Omnibus (GEO) database was used to identify the key genes and pathways. Differentially expressed genes (DEGs) were mined using the limma package in R language. Next, ARGs were obtained by matching DEGs and autophagy-related genes from GeneCard using Venn diagrams. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of ARGs were described using clusterProfiler and org.Hs.eg.db in R. Moreover, hub ARGs were screened out through protein-protein interaction (PPI), gene-microRNAs, and gene-transcription factors (TFs) networks then visualized using Cytoscape. Of note, the rat model of diabetic ED was established to validate some hub ARGs with qRT-PCR and Western blots. RESULTS: Twenty ARGs were identified from four ED samples and eight non-ED samples. GO analysis revealed that molecular functions (MF) of upregulated ARGs were mainly enriched in nuclear receptor activity. Also, MF of downregulated ARGs were mainly enriched in oxidoreductase activity, acting on NAD(P)H and heme proteins as acceptors. Moreover, six hub ARGs were identified by setting high degrees in the network. Additionally, hsa-mir-24-3p and hsa-mir-335-5p might play a central role in several ARGs regulation, and the transcription factors-hub genes network was centered with 13 ARGs. The experimental results further showed that the expression of Notch1, NOS3, and CDKN2A in the diabetic ED group was downregulated compared to the control. CONCLUSIONS: Our study deepens the autophagy-related mechanistic understanding of endothelial dysfunction of ED. NOTCH1, CDKN2A, and NOS3 are involved in the regulation of endothelial dysfunction and may be potential therapeutic targets for ED by modulating autophagy.

Erectile Dysfunction in Type-2 Diabetes Mellitus Patients: Predictors of Early Detection and Treatment.

PURPOSE: To identify risk factors and potential predictors of erectile dysfunction (ED) in type-2 diabetes mellitus (T2DM) patients for early detection and treatment. METHODS: A retrospective cohort was used to assess the clinical data of 105 diabetic patients with ED from May 2019 to April 2020 age-matched to 105 diabetic patients without ED. Potential risk factors that could contribute to ED were compared between the groups. Erectile function was evaluated using the International Index of Erectile Function-5 questionnaire. RESULTS: There were higher rates of diabetic peripheral neuropathy (p = 0.036) and retinopathy (p < 0.001), longer duration of diabetes (p < 0.001), lower estimated glomerular filtration rate (p = 0.010) values, and higher uric acid (p < 0.001) and C-reactive protein (p = 0.001) levels in the ED group compared to the non-ED group. Multivariate logistic analysis identified uric acid, diabetic retinopathy, and T2DM course as independent predictors of diabetic ED. Diabetics with retinopathy and T2DM for ≥49 months were 3.028 and 3.860 times more likely to have ED, respectively. Uric acid values ≥392.5 µmol/L were associated with 18.638 times greater risk of having ED, though the values were within normal range. CONCLUSION: In T2DM patients, higher uric acid (≥392.5 µmol/L), longer diabetes duration (≥49 months), and the presence of diabetic retinopathy were important and reliable predictors for diabetic ED. For patients who have high risk factors for developing ED, diligent screening and early treatment are necessary.

Corrigendum to "Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia".

[This corrects the article DOI: 10.1155/2020/7286958.].

Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia.

Hyperlipidemia is considered one of the most important risk factors for erectile dysfunction (ED). To determine the effect of sodium tanshinone IIA sulfonate (STS) as an antioxidant agent on ED in high-fat diet- (HFD-) induced hyperlipidemia in rats and to investigate if STS administration could improve erectile function via hydrogen sulfide (H2S) production by inhibition of oxidative stress. Hyperlipidemia was induced in Sprague-Dawley rats by feeding HFD for 16 weeks. The rats were randomly divided into 3 groups: control, HFD, and HFD treated with STS (10 mg/kg/day for 12 weeks, intraperitoneal injection). Erectile function including intracavernosal pressure (ICP), H2S production, and antioxidant capacity was assessed. In addition, cavernosal smooth muscle cells (CSMC) isolated from SD rats were pretreated with STS in vitro and exposed to H2O2. Expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), activity of antioxidant enzymes, and H2S-generating enzymes within CSMC were examined. ICP was significantly decreased in HFD rats compared with control. In addition, decreased H2S production and expression of cystathionine É£-lyase (CSE) and cystathionine ß-synthase (CBS) associated with increased oxidative stress were observed in the penile tissue of HFD rats. However, all these changes were reversed by 16 weeks after STS administration. STS also increased antioxidant defense as evidenced by increased expression of Nrf2/HO-1 in the penile tissue of HFD rats. In CSMC, pretreatment with STS attenuated the decreased expression of CSE and CBS and H2S production by H2O2. STS exerted similar protective antioxidative effect as shown in the in vivo hyperlipidemia model. The present study demonstrated the redox effect of STS treatment on ED via increased H2S production in HFD-induced hyperlipidemia rat model by increased antioxidant capacity via activation of the Nrf2/HO-1 pathway, which provides STS potential clinical application in the treatment of hyperlipidemia-related ED.

Recommended antibiotic prophylaxis regimen in retrograde intrarenal surgery: evidence from a randomised controlled trial.

OBJECTIVE: To study the incidence of postoperative systemic inflammatory response syndrome (SIRS) following different antibiotic prophylaxis (ABP) regimens in retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS: Single-centre, randomised, controlled trial (August 2014-September 2017) including 426 patients with renal stones with preoperative sterile urine managed by RIRS (ClinicalTrials.gov NCT02304822). Different ciprofloxacin-based ABP regimens were used and included a zero dose, single dose (30 min before surgery) or two doses (first dose at 30 min before RIRS and additional dose within 6 h after RIRS). The incidence of SIRS was compared using intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: Each group enrolled 142 patients. In the ITT analysis, a zero dose of ABP was statistically similar to the two ABP regimes for the incidence of SIRS (9.9% vs single dose 4.9%, P = 0.112; vs two doses 4.2%, P = 0.062). There were also no relevant differences across groups in the PP analysis; no urosepsis was recorded. In subgroup analysis with stratification by stone area, the three regimens all had a low and similar incidence of SIRS for stones of ≤200 mm2 in the ITT analysis with a sufficient power value (5.4% vs 6.2% vs 3.6%, P = 0.945 vs single dose and P = 0.553 vs two doses). However, there was a greater chance of SIRS in patients who received no ABP with stones of >200 mm2 (18% vs single dose 4.3%, P = 0.036; vs two doses 5.5%, P = 0.044). Similar trends were seen in the PP analysis. CONCLUSIONS: For patients with preoperative sterile urine, ABP is not strongly recommended in patients with stones of ≤200 mm2 , but for stones >200 mm2 single-dose ABP is still required.

The role of super-mini percutaneous nephrolithotomy (SMP) in the treatment of symptomatic lower pole renal stones (LPSs) after the failure of shockwave lithotripsy (SWL) or retrograde intrarenal surgery (RIRS).

To assess the safety and efficacy of super-mini percutaneous nephrolithotomy (SMP) in the treatment of symptomatic lower pole renal stones (LPSs) after the failure of shockwave lithotripsy (SWL) or retrograde intrarenal surgery (RIRS), we retrospectively evaluated 44 patients with symptomatic LPSs with previously failed SWL or RIRS and consequently underwent SMP from October 2014 to March 2016. The percutaneous renal access was performed 12-14F with C-arm fluoroscopy or ultrasonographic guidance. Stone disintegration was performed using either Holmium laser or pneumatic lithotripter. Perioperative parameters along with operations were assessed in detail. A total of 44 patients (mean age 49.1 ± 13.7 years) were included in the study. Stone size was 18.4 ± 6.0 mm (range 9-29), operative time was 63.9 ± 32.7 min (range 14-145) and hospital stay was 2.8 ± 1.2 days (range 1-5). The hemoglobin drop was 12.4 ± 8.8 g/L (range 0-31), and no patients required blood transfusion. Complete stone-free status was achieved in 40 (90.9%) patients. Clinically insignificant residual fragments were observed in three (6.8%) patients and only one (2.3%) patient had a 6 mm residual calculus. A total of three minor complications (urinary tract infection, hemorrhage resolved by hemostatics and renal colic requiring analgesics) were observed postoperatively. For symptomatic LPSs after the failure of SWL or RIRS, SMP is a safe and efficient auxiliary option and even might be an alternative to SWL or RIRS, while further considering the stone-free rates and stone-related events.

The Influence of Super-Mini Percutaneous Nephrolithotomy on Renal Pelvic Pressure In Vivo.

OBJECTIVE: Renal pelvic pressure (RPP) is expected to rise during percutaneous procedures. A very small tract size was expected to bring high RPP, and super-mini percutaneous nephrolithotomy (SMP) uses a 14F sheath, which is even smaller than that used in mini-percutaneous nephrolithotomy, so the RPP in SMP was more worrisome. Interestingly, the sheath had suction, which aimed to decrease the RPP, so we measured the RPP in an in vivo model to explore the relationship of implying negative pressure through the sheath with the RPP. METHODS: Seventy-four consecutive patients were enrolled for RPP measurement during SMP between April 2016 and July 2017. Prospective RPP measurements were recorded using the MINDRAY-PM9000 monitor by connecting its baroceptor of the invasive blood pressure channel to a retrogradely inserted renal pelvic open-ended ureteric catheter. RPP data were collected each second by a computer program. All data were evaluated statistically with SPSS 13.0 software. RESULTS: During SMP with a 14F irrigation-suction sheath, the average RPP was 19.51 ± 5.83 mm Hg. The median accumulative time of RPP ≥30 mm Hg was 55 (3-345) seconds. Postoperative fever was recorded in four patients (5.4%). A receiver operating characteristic -curve analysis showed that when suction pressure was set to 0.03 Mpa (≈230 mm Hg), irrigation pressure between 200 and 250 mm Hg, and the irrigation flow to 320 mL/minute, the accumulative high RPP was more likely <50 seconds, and the sensitivity and specificity were 75.0% and 66.7%, respectively. CONCLUSIONS: The RPP in SMP remains <30 mm Hg. Controlling the pressures as well as the flow of irrigating saline is important for the safety and efficiency of percutaneous procedures.

Super-mini percutaneous nephrolithotomy (SMP) vs retrograde intrarenal surgery for the treatment of 1-2 cm lower-pole renal calculi: an international multicentre randomised controlled trial.

OBJECTIVES: To compare the safety and effectiveness of super-mini-percutaneous nephrolithotomy (SMP) and retrograde intrarenal surgery (RIRS) for the treatment of 1-2 cm lower-pole renal calculi (LPC). PATIENTS AND METHODS: An international multicentre, prospective, randomised, unblinded controlled study was conducted at 10 academic medical centres in China, India, and Turkey, between August 2015 and June 2017. In all, 160 consecutive patients with 1-2 cm LPC were randomised to receive SMP or RIRS. The primary endpoint was stone-free rate (SFR). Stone-free status was defined as no residual fragments of ≥0.3 cm on plain abdominal radiograph of the kidneys, ureters and bladder, and ultrasonography at 1-day and on computed tomography at 3-months after operation. Secondary endpoints included blood loss, operating time, postoperative pain scores, auxiliary procedures, complications, and hospital stay. Postoperative follow-up was scheduled at 3 months. Analysis was by intention-to-treat. The trial was registered at http://clinicaltrials.gov/ (NCT02519634). RESULTS: The two groups had similar baseline characteristics. The mean (sd) stone diameters were comparable between the groups, at 1.50 (0.29) cm for the SMP group vs 1.43 (0.34) cm for the RIRS group (P = 0.214). SMP achieved a significantly better 1-day and 3-month SFR than RIRS (1-day SFR 91.2% vs 71.2%, P = 0.001; 3-months SFR 93.8% vs 82.5%, P = 0.028). The auxiliary procedure rate was lower in the SMP group. RIRS was found to be superior with lower haemoglobin drop and less postoperative pain. Blood transfusion was not required in either group. There was no significant difference in operating time, hospital stay, and complication rates, between the groups. CONCLUSIONS: SMP was more effective than RIRS for treating 1-2 cm LPC in terms of a better SFR and lesser auxiliary procedure rate. The complications and hospital stay were comparable. RIRS has the advantage of less postoperative pain.

Comparison of super-mini PCNL (SMP) versus Miniperc for stones larger than 2 cm: a propensity score-matching study.

PURPOSE: To compare the efficacy and safety of Super-mini percutaneous nephrolithotomy (SMP, F12-F14) and Miniperc (F18) in the treatment of renal stones of 2-4 cm in size. METHODS: A prospective comparative analysis of outcomes of patients who underwent SMP and Miniperc for treatment of 2-4 cm renal stones was conducted between July 2014 and January 2017. Demographic data, stone criteria, operative technique, complications, blood transfusion, hemoglobin decrease, stone-free rate (SFR) and length of hospital stay were compared between the two groups. Propensity score-matching (PSM) analysis was performed to further compare the outcomes between the two groups. RESULTS: 79 and 257 patients underwent SMP and Miniperc, respectively. After matching, 73 patients in each group were included. The stone burden was comparable for both groups (3.0 ± 1.1 vs 3.2 ± 0.7 cm, p = 0.577). Mean operation time was not significant different between two groups (p = 0.115), while the hospital stay of SMP was much shorter than Miniperc (2.6 ± 1.4 vs 5.2 ± 1.8, p < 0.0001). Both groups had similar SFRs in postoperative 1 day and at 1 month follow-up (p = 0.326, p = 0.153), while SMP achieved a markedly higher tubeless rate than Miniperc (84.9 vs 47.9%, p < 0.0001). The total complication rate was significantly lower in SMP (16.4 vs 41.1%, p = 0.0001), and the SIRS rate was markedly lower in SMP group (1.4 vs 12.3%, p = 0.009). CONCLUSIONS: SMP is equally effective as Miniperc in the treatment of moderate renal calculi, and has the significant advantage in hospital duration and tubeless rate.

miR-195 inhibits cell proliferation and angiogenesis in human prostate cancer by downregulating PRR11 expression.

hsa-miR-195-5p (miR-195) has been proven to be a critical regulator in the progression of prostate cancer (PCa). To identify additional targets and molecular functions of miR-195, we overexpressed miR-195 by transient oligonucleotide transfection in DU145 and LNCaP cells and examined the effects. RNA-based microarray and dual-luciferase assays were carried out to identify novel targets of miR-195, while in vitro functional assays, a subcutaneous xenograft model, tissue microarray (TMA) analysis and a cohort of publicly available data (Taylor cohort) were used to investigate the biological function and clinical value of miR-195 targeting. The results shown that miR-195 overexpression could markedly suppress cellular proliferation and tube formation compared with miR-negative control. The RNA-based microarray identified a total of 153 differentially regulated genes with fold changes of ≤|1.5|, including 138 (90.2%) downregulated and 15 (9.8%) upregulated genes. Among the downregulated genes, we found that proline-rich protein 11 (PRR11) combined with miR-195 expression (miR-195/PRR11) could be used as an independent predictor of the risk of biochemical recurrence in the Taylor cohort. Additionally, the dual-luciferase assay identified PRR11 as a novel target of miR-195, and the in vitro assays indicated that PRR11 abrogated the suppressive effects of miR-195 on cell proliferation, tube formation and cell cycling. Furthermore, the subcutaneous tumor xenograft model indicated that knockdown of PRR11 inhibited xenograft growth and angiogenesis, while the results of the TMA and Taylor cohort analyses collectively demonstrated that PRR11 expression was upregulated in aggressive tumors and is associated with poor clinical outcome. Taken together, these findings further illustrate the suppressive role of miR-195 in PCa, and indicate a novel role of PRR11 in PCa. Importantly, the newly identified miR-195/PRR11 axis may aid with identifying potential therapeutic targets in PCa.

Antibiotic prophylaxis in ureteroscopic lithotripsy: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To explore the efficacy of antibiotic prophylaxis and the different strategies used to prevent infection in ureteroscopic lithotripsy (URL) by conducting a systematic review and meta-analysis. MATERIALS AND METHODS: A systematic literature search using Pubmed, Embase, Medline, the Cochrane Library, and the Chinese CBM, CNKI and VIP databases was performed to find comparative studies on the efficacy of different antibiotic prophylaxis strategies in URL for preventing postoperative infections. The last search was conducted on 25 June 2017. Summarized unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the efficacy of different antibiotic prophylaxis strategies. RESULTS: A total of 11 studies in 4 591 patients were included in this systematic review and meta-analysis. No significant difference was found in the risk of postoperative febrile urinary tract infections (fUTIs) between groups with and without antibiotic prophylaxis (OR: 0.82, 95% CI 0.40-1.67; P = 0.59). Patients receiving a single dose of preoperative antibiotics had a significantly lower risk of pyuria (OR: 0.42, 95% CI 0.25-0.69; P = 0.0007) and bacteriuria (OR: 0.25, 95% CI 0.11-0.58; P = 0.001) than those who did not. Intravenous antibiotic prophylaxis was not superior to single-dose oral antibiotic prophylaxis in reducing fUTI (OR: 1.00, 95% CI 0.26-3.88; P = 1.00). CONCLUSIONS: We concluded that preoperative antibiotic prophylaxis did not lower the risk of postoperative fUTI, but a single dose could reduce the incidence of pyuria or bacteriuria. A single oral dose of preventive antibiotics is preferred because of its cost-effectiveness. The efficacy of different types of antibiotics and other strategies could not be assessed in our meta-analysis. Randomized controlled trials with a larger sample size and more rigorous study design are needed to validate these conclusions.

Percutaneous nephrolithotomy: position, position, position!

Percutaneous nephrolithotomy (PCNL) is the regular surgery for treating large or complex renal stones. Since its first inception, many variations have come in the approach including the modifications of patient position. The prone position is traditionally used, and subsequently, variations in prone and supine technique have been proposed and assessed over time. In an attempt to provide comprehensive information about the strategy applications of patient's position, the present review describes the position-related general basis, and provides a literature review of the pros and cons of various positions from a surgical and anaesthetic point of view. Latest evidence has shown the major advantages of supine PCNL compared with standard prone PCNL to be as follows: optimal cardiovascular and airway control; shorter operation time due to lack of the need for repositioning; opportunity for a combined retrograde approach. However, the prone position provides a broader surface area for percutaneous access; a wider space for manipulating the nephroscope and lithotripters; and opportunity for bilateral simultaneous PCNL. To overcome their respective limitations, various positioning modifications have been proposed. However, most reports are based on case series and/or have not obtained their results in a randomized controlled fashion and/or have not been analysed according to stone complexity and particular body status (e.g. obesity, etc.), thereby limiting the ability to make strong recommendations. One important caveat is that endourology training of supine PCNL would increase supine popularization, and the prone ureteroscopic technique would overcome the difficulty of endoscopic combined intrarenal surgery in the prone position. Thereby, adequate training in the different techniques for PCNL is important for optimizing the indications and treatment outcomes.

Prospective Comparative Study of the Efficacy and Safety of New-Generation Versus First-Generation System for Super-Mini-Percutaneous Nephrolithotomy: A Revolutionary Approach to Improve Endoscopic Vision and Stone Removal.

PURPOSE: The study sought to compare the procedural and clinical results of super-mini-percutaneous nephrolithotomy (SMP) with the use of first- and new-generation devices. METHODS: A prospective, comparative cohort study was carried out between February 2013 and January 2017. Patients who underwent either first- or new-generation SMP were eligible for the study. Inclusion criteria were adult patients with renal stone <4 cm, or in pediatric patients with renal stone <2.5 cm with a history of failed extracorporeal shockwave lithotripsy. The primary outcome of the present study was the operating time, which was calculated from the starting of percutaneous puncture to the wound closure. Secondary outcomes were the stone-free rate (SFR), blood loss (hemoglobin decrease), hospital stay, and postoperative complications. RESULTS: One hundred fifty-six consecutive patients who underwent SMP for treatment of renal stones were eligible for the study, with the first 85 patients undergoing SMP with the first-generation device, and the remaining 71 consecutive patients being treated with the new-generation SMP system. The two groups of patients had comparable demographic data, including age, BMI, stone size, Guy's score, stone location, comorbidities, grade of hydronephrosis, and history of urinary tract infection. The new-generation SMP had a shorter operation time (39.3 vs 50.5 min, p = 0.016) and shorter postoperative hospitalization time (2.1 vs 3.0 days, p < 0.001) than the first-generation SMP. No significant difference existed between the two groups for SFR, hemoglobin decrease, and tubeless rate. The overall operative complication rates using the Clavien-Dindo grading system were similar between the two cohorts of patients. CONCLUSION: The clinical outcomes of the new-generation SMP in patients with moderate-sized renal stone were comparable when compared with the first-generation SMP. New-generation SMP system using an irrigation/suction sheath improved intraoperative irrigation, a more efficient hydrodynamic mechanism for retrieval of fragments. This may account for the shorter operative time than the first-generation SMP system demonstrated in this study.

The new generation super-mini percutaneous nephrolithotomy (SMP) system: a step-by-step guide.

OBJECTIVE: To present our novel miniaturised endoscopic system and describe a step-by-step guide for successful implementation of the super-mini percutaneous nephrolithotomy (SMP). PATIENTS AND METHODS: The new-generation SMP endoscopic system consists of (i) a 40 000-pixel super-mini nephroscope with an 8.0-F outer diameter and 7.5-F inner diameter dismountable sheath, and (ii) a newly designed irrigation-suction sheath available in either 12 F or 14 F. The irrigation-suction sheath is a two-layered metal structure. The key feature of the irrigation-suction sheath is to allow irrigation and suction respectively (the inflow through the space between the two layers of the sheath, the outflow through the central lumen of the sheath). This property improves irrigation and stone clearance despite reduced instrument dimension. In all, 59 patients with renal stones underwent new-generation SMP between April 2016 and December 2016. The percutaneous tract dilatation was carried out to 14 F. Lithotripsy was performed using either holmium laser or a pneumatic lithotripter. Stone fragments were sucked out by vacuum suctioning through the sheath. A nephrostomy tube or JJ stent was placed only if clinically indicated. Low-dose computed tomography was performed to assess the stone-free status on the morning after the procedure. RESULTS: The mean stone burden was 2.4 cm. Of the 59 patients, nine had diabetes and five had hypertension. SMP was completed successfully in all patients with a mean operation duration of 32.9 min and a mean haemoglobin decrease of 13 g/L. The stone-free rate was 91.5%. Complications occurred in 5.1% of the patients, all of them were Clavien-Dindo Grade I (minor fever managed by antipyretic therapy), and no transfusions were needed. CONCLUSION: The new-generation SMP system is safe, feasible, and effective for managing renal calculi of <3 cm, with the advantages of a small percutaneous tract, less blood loss, high efficacy in stone clearance, improved visual field, short operation duration, and ease of operating.

Predictors for uroseptic shock in patients who undergo minimally invasive percutaneous nephrolithotomy.

To identify risk factors that can predict which patient is likely to progress from systemic inflammatory response syndrome (SIRS) to uroseptic shock after minimally invasive percutaneous nephrolithotomy (MPCNL) for the upper urinary tract stones. We retrospectively reviewed 156 patients who suffered infectious complications after MPCNL from March 2014 to February 2016. Perioperative risk factors that could potentially contribute to uroseptic shock were compared to those of patients with only SIRS. 135 of the 156 patients developed to SIRS only, the remaining 21 patients progressed to uroseptic shock. The rate of positive preoperative urine nitrite was significantly higher (p < 0.001), stone diameter was larger (p = 0.015) and operative time was longer (p < 0.001) in uroseptic shock group. Multivariable logistic analysis showed that preoperative urine nitrite (OR 10.570, p = 0.025), stone size (OR 11.512, p = 0.009) and postoperative blood leukopenia (OR 0.009, p < 0.001) were independently related to uroseptic shock. Moreover, ROC curve analysis showed that white blood count threshold within the first 3 h of uroseptic shock was 2.98 × 109/L. The sensitivity and specificity of leukocyte count in predicting uroseptic shock were 90.5 and 92.6%, respectively. Preoperative urine nitrite, stone size and postoperative leukocyte count are statistically linked to uroseptic shock after MPCNL. Leukopenia of less than 2.98 × 109/L within 3 h after MPCNL can be a predictor for uroseptic shock. For patients who have high risk factors for developing uroseptic shock, the white blood count should be measured within 3 h after MPCNL.