Upregulation of FGF7 Induced Intravesical Prostatic Protrusion of Benign Prostatic Hyperplasia via the ERK1/2 Signaling Pathway.

INTRODUCTION: Intravesical prostatic protrusion (IPP) has been reported to be associated with bladder outlet obstruction and is the main cause of lower urinary tract symptoms (LUTS) during the development of benign prostatic hyperplasia (BPH). However, the molecular mechanism of IPP remains unclear. METHODS: Clinical data analysis was performed to analyze the association between IPP and long-term complications in patients with BPH. RNA sequencing was performed on prostate tissues (IPP or not). Stromal cells were obtained from IPP-derived primary cultures to explore the molecular mechanism of IPP formation. Cell proliferation was evaluated by a CCK-8 assay. Multiple proteins in the signaling pathway were assessed using Western blot. RESULTS: First, we confirmed that IPP is a prognostic factor for long-term complications in patients with BPH. Then, we observed that FGF7 was upregulated in both IPP tissues and IPP primary stromal cells through immunohistochemistry, Western blot, and quantitative real-time PCR. Furthermore, FGF7 was significantly upregulated in high IPP-grade prostate tissues. The coculture experiments showed that the downregulation of FGF7 in IPP-derived stromal cells inhibited the proliferation and migration of the prostate epithelial cells. Additionally, FGF7 was bound to FGFR2 to induce the epithelial-mesenchymal transition process through binding to FGFR2. RNA sequencing analysis also revealed the activation of the MAPK/ERK1/2 signaling pathway. The MAPK/ERK1/2 was downregulated by a specific inhibitor affecting the FGF7 stimulation in vitro. CONCLUSIONS: Our data reveal a novel amplification effect, i.e., stromal cell-derived FGF7 promotes epithelial cell proliferation and stromal cell phenotype, ultimately inducing IPP formation. Targeting FGF7 can significantly reduce epithelial to stromal transition and provide a potential therapeutic target for BPH progression.

ROS-NLRP3 signaling pathway induces sterile inflammation after thulium laser resection of the prostate.

The sterile inflammation (SI) of the urinary tract is a common problem requiring serious consideration after prostatectomy. This study mainly focuses on the role of the reactive oxygen species-NLR family, pyrin domain-containing 3 (ROS-NLRP3) signaling pathway in SI after thulium laser resection of the prostate (TmLRP). Urinary cytokines were determined in patients who received TmLRP, and heat shock protein 70 (HSP70) was detected in the resected tissues. The involvement of ROS signaling in HSP70-induced inflammation was explored in THP-1 cells with or without N-acetyl- l-cysteine (NAC) pretreatment. The function of NLRP3 and Caspase-1 was determined by Western blot analysis, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction. These phenomena and mechanisms were verified by the beagle models that received TmLRP. Clinical urine samples after TmLRP showed high expression of inflammatory factors and peaked 3-5 days after surgery. The high expression of HSP70 in the resected tissues was observed. After HSP70 stimulation, the expression of ROS, NLRP3, Caspase-1, and interleukin-18 (IL-18) increased significantly and could be reduced by ROS inhibitor NAC. The expression of IL-1ß and IL-18 could be inhibited by NLRP3 or Caspase-1 inhibitors. In beagle models that received TmLRP, HSP70, NLRP3, Caspase-1, IL-1ß, and IL-18 were highly expressed in the wound tissue or urine, and could also be reduced by NAC pretreatment. Activation of the ROS-NLRP3 signaling pathway induces SI in the wound after prostatectomy. Inhibition of this pathway may be effective for clinical prevention and treatment of SI and related complications after prostatectomy.

[Effects of all-trans retinoic acid on the macrophage function of prostatic stromal cells].

Objective: To investigate the effects of all-trans retinoic acid (ATRA) on prostatic stromal cells during wound repair after prostatectomy in vitro. METHODS: Each of the M1 and M2 types of monocytic macrophage (THP-1) cells were divided into an experimental, a control and a non-activated group, the M1 macrophages of the former two groups activated by PMA and IFNγ, and the M2 macrophages by PMA and IL-4, respectively. The cells in the two experimental groups were treated with all-trans retinoic acid (ATRA) at 100 nmol/L, followed by detection of the expressions of IL-10, IL-12, IL-6, TNF-α and TGF-ß in the supernatant by ELISA. The supernatant was co-cultured with primarily cultured prostatic stromal cells or vascular endothelial cells in different groups. The expressions of RARα, RARß, RARγ, Arg1, Mmp9 and Soat1 in the macrophages were determined by PCR. The influence of the macrophages on the function of the stromal cells was analyzed by gel shrinkage test, scratch test and vascular endothelial cell tubular vascular formation test. The expression levels of Arg1 mRNA were reexamined under the action of RAR receptor subtype inhibitors. RESULTS: Compared with the control, the M2 macrophages treated with ATRA showed dramatically up-regulated expressions of IL-10 (ï¼»213.38 ± 2.02ï¼½ vs ï¼»298.22 ± 1.70ï¼½ pg/ml, P < 0.01) and TGF-ß (ï¼»185.37 ± 1.33ï¼½ vs ï¼»246.00 ± 2.14ï¼½ pg/ml, P < 0.01). The ATRA-treated macrophage supernatant enhanced the contraction and migration of the prostatic stromal cells and tubular formation of the vascular endothelial cells. The mRNA levels of Arg1 and RARß were significantly increased in the experimental group, and RARß was further confirmed to be the key receptor subtype in this process. CONCLUSIONS: ATRA activates prostatic stromal cells and enhances their migration and angiogenesis by acting on macrophages via RARß.

CAFs-derived MFAP5 promotes bladder cancer malignant behavior through NOTCH2/HEY1 signaling.

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment and contribute to tumor cell proliferation and metastasis. Microfibrillar-associated protein 5 (MFAP5), a component of elastic microfibers and an oncogenic protein in several types of tumors, is secreted by CAFs. However, the role of MFAP5 in the bladder cancer remains unclear. Here, we report that MFAP5 is upregulated in bladder cancer and is associated with poor patient survival. Downregulation of MFAP5 in CAFs led to an impairment in proliferation and invasion of bladder cancer cells. Luciferase reporter assays and electrophoretic mobility shift assays (EMSA) showed QKI directly downregulates MFAP5 in CAFs. In addition, CAFs-derived MFAP5 led to an activation of the NOTCH2/HEY1 signaling pathway through direct interaction with the NOTCH2 receptor, thereby stimulating the N2ICD release. RNA-sequencing revealed that MFAP5-mediated PI3K-AKT signaling activated the DLL4/NOTCH2 pathway axis in bladder cancer. Moreover, downregulation of NOTCH2 by short hairpin RNA or the inactivating anti-body NRR2Mab was able to reverse the adverse effects of MFAP5 stimulation in vitro and in vivo. Together, these results demonstrate CAFs-derived MFAP5 promotes the bladder cancer proliferation and metastasis and provides new insight for targeting CAFs as novel diagnostic and therapeutic strategy.

RNA-binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression.

The androgen receptor (AR) pathway is critical for prostate cancer carcinogenesis and development; however, after 18-24 months of AR blocking therapy, patients invariably progress to castration-resistant prostate cancer (CRPC), which remains an urgent problem to be solved. Therefore, finding key molecules that interact with AR as novel strategies to treat prostate cancer and even CRPC is desperately needed. In the current study, we focused on the regulation of RNA-binding proteins (RBPs) associated with AR and determined that the mRNA and protein levels of AR were highly correlated with Musashi2 (MSI2) levels. MSI2 was upregulated in prostate cancer specimens and significantly correlated with advanced tumor grades. Downregulation of MSI2 in both androgen sensitive and insensitive prostate cancer cells inhibited tumor formation in vivo and decreased cell growth in vitro, which could be reversed by AR overexpression. Mechanistically, MSI2 directly bound to the 3'-untranslated region (UTR) of AR mRNA to increase its stability and, thus, enhanced its transcriptional activity. Our findings illustrate a previously unknown regulatory mechanism in prostate cancer cell proliferation regulated by the MSI2-AR axis and provide novel evidence towards a strategy against prostate cancer.

Di-n-butyl phthalate (DBP) reduces epithelial-mesenchymal transition via IP3R in hypospadias during maternal exposure.

OBJECTIVE: This study focused on the oxidative stress effect of di-n-butyl phthalate (DBP) on development of the urinary system. METHODS: We examined the mRNA expression of genital tubercle (GT) in control and DBP induced hypospadias group by Affymetrix Rat 230 2.0 Array. Real-time PCR and Western Blot were used to detect the protein and mRNA expression levels of inositol-1,4,5-triphate-receptor (IP3R) and epithelial-mesenchymal-transition (EMT)-related molecular markers, such as E-cadherin, ß-Catenin, Snail, N-cadherin, in the GT of hypospadiac male rats and controls. The results of array were further confirmed in vitro. The changes of intracellular calcium concentration in urethral epithelial cells were detected by Fluo-3-AM before and after DBP treatment. The levels of reactive oxygen species (ROS) in urethral epithelial cells were measured by DCFH-DA with different concentrations of DBP (0, 1, 10, 100 µmol/L) treatment. RESULTS: The mRNA expression profiles of GT in control and DBP induced hypospadias group showed high expression of IP3R and the abnormalities of EMT. Compared to the control group, the expression levels of IP3R, E-cadherin and ß-Catenin increased at both the protein and mRNA levels. However the expression levels of Snail and N-cadherin decreased. The intracellular calcium concentration increased significantly after DBP treatment. The effect of DBP on urethral epithelial cells was linked to the generation of oxidative stress. CONCLUSION: DBP can influence the development of GT through its oxidative stress effect, which significantly increases the concentration of calcium and inhibits EMT in urethral epithelial cells, and block the fusion process of urethral groove, causing the occurrence of hypospadias. This study provides a new understanding of DBP's molecular mechanisms on hypospadias and may lead to new treatment strategies for the disease.

[Bladder outlet obstruction index alone is not reliable for the diagnosis of benign prostate hyperplasia].

OBJECTIVE: To evaluate the clinical application value of the bladder outlet obstruction index (BOOI) in the diagnosis of BPH. METHODS: We retrospectively analyzed the urodynamic parameters and BOOI of 199 cases of BPH diagnosed from July 2016 to September 2018, which were divided into a BOO (n = 119), a suspected BOO (n = 39) and a non-BOO group (n = 41) based on the BOOI. We obtained the prostate volume (PV), IPSS, IPSS-voiding symptom score (IPSS-VS), quality of life score (QOL), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) from the patients, compared them among the three groups and analyzed their correlation to BOOI using Pearson's linear correlation analysis. RESULTS: No statistically significant differences were observed in age (P = 0.195), PSA (P = 0.380), IPSS (P = 0.380), IPSS-VS (P = 0.380), QOL (P = 0.380), Qmax (P = 0.380) and PVR (P = 0.912) among the three groups of patients, but PV was remarkably larger in the BOO than in the suspected BOO and non-BOO groups (ï¼»58.8 ± 30.0ï¼½ vs ï¼»49.8 ± 33.9ï¼½ and ï¼»45.5 ± 26.0ï¼½ ml, P = 0.031). Pearson's linear correlation analysis showed that BOOI was not correlated significantly to IPSS (r = －0.020, P = 0.778), IPSS-VS (r= －0.013, P = 0.853), QOL (r = －0.107, P = 0.132), Qmax (r = －0.130, P = 0.066) or PVR (r = －0.056, P = 0.433), nor obviously to PV (|r| = 0.178<0.4) though with P = 0.012. CONCLUSIONS: BOOI is not significantly correlated to PV, IPSS, IPSS-VS, QOL, Qmax or PVR, and therefore BOO cannot be diagnosed exclusively with BOOI.

QKI-6 inhibits bladder cancer malignant behaviours through down-regulating E2F3 and NF-κB signalling.

Quaking homolog (QKI) is a member of the RNA-binding signal transduction and activator of proteins family. Previous studies showed that QKI possesses the tumour suppressor activity in human cancers by interacting with the 3'-untraslated region (3'-UTR) of various gene transcripts via the STAR domain. This study first assessed the association of QKI-6 expression with clinicopathological and survival data from bladder cancer patients and then investigated the underlying molecular mechanisms. Bladder cancer tissues (n = 223) were subjected to immunohistochemistry, and tumour cell lines and nude mice were used for different in vitro and in vivo assays following QKI-6 overexpression or knockdown. QKI-6 down-regulation was associated with advanced tumour TNM stages and poor patient overall survival. QKI-6 overexpression inhibited bladder cancer cell growth and invasion capacity, but induced tumour cell apoptosis and cell cycle arrest. Furthermore, ectopic expression of QKI-6 reduced tumour xenograft growth and expression of proliferation markers, Ki67 and PCNA. However, knockdown of QKI-6 expression had opposite effects in vitro and in vivo. QKI-6 inhibited expression of E2 transcription factor 3 (E2F3) by directly binding to the E2F3 3'-UTR, whereas E2F3 induced QKI-6 transcription by binding to the QKI-6 promoter in negative feedback mechanism. QKI-6 expression also suppressed activity and expression of nuclear factor-κB (NF-κB) signalling proteins in vitro, implying a novel multilevel regulatory network downstream of QKI-6. In conclusion, QKI-6 down-regulation contributes to bladder cancer development and progression.

Heat injured stromal cells-derived exosomal EGFR enhances prostatic wound healing after thulium laser resection through EMT and NF-κB signaling.

BACKGROUND: This study investigated shallow heat injury to prostate stromal fibroblasts and epithelial cells and their interaction to regulate the wound healing and the underlying molecular events. METHODS: Prostate stromal fibroblasts and epithelial cells were cultured individually or cocultured and subjected to shallow heat injury for assessments of cell proliferation, migration, apoptosis, cell cycle distribution, and gene expression. The supernatant of heat-injured WPMY-1 cells was collected for exosome extraction and assessments. Furthermore, beagle dogs received thulium laser resection of the prostate (TmLRP) and randomly divided into Gefitinib, GW4869, and control treatment for the histological analysis, tissue re-epithelialization, and epidermal growth factor receptor (EGFR) expression on the prostatic wound surface. Immunofluorescence was to evaluate p63-positive basal progenitor cell trans-differentiation and macrophage polarization and ELISA was to detect cytokine levels in beagles' urine. RESULTS: Shallow heat injury caused these cells to enter a stressed state and enhanced their crosstalk. The prostate stromal fibroblasts produced and secreted more exosomal-EGFR and other cytokines and chemokines after shallow heat injury, resulting in increased proliferation and migration of prostate epithelial cells during wound healing. The wound healing of the canine prostatic urethra following the TmLRP procedure was slower in the Gefitinib and GW4869 treatment group than in the control group of animals. Immunofluorescence and ELISA showed that reduced EGFR expression interrupted macrophage polarization but increased the inflammatory response. CONCLUSIONS: Shallow heat injury was able to promote the interaction of prostate stromal cells with prostate epithelial cells to enhance wound healing. Stromal-derived exosomal-EGFR plays a crucial role in the balance of the macrophage polarization and prostatic wound healing.

M1 macrophage mediated increased reactive oxygen species (ROS) influence wound healing via the MAPK signaling in vitro and in vivo.

Thulium laser resection of the prostate (TmLRP), a major treatment for benign prostatic hyperplasia (BPH), has several postoperative complications that affect the patients' quality of life. The aim of this study was to investigate the effect of the M1 macrophage-secreted reactive oxygen species (ROS) on prostatic wound healing, and the role of MAPK signaling in this process. A co-culture model in vitro was established using macrophages and prostate epithelial or stromal cells. Cell proliferation, migration, apoptosis, MAPK pathway-related gene expression levels were evaluated by standard assays. In addition, an in vivo model of prostatectomy was established in beagles by subjecting them to TmLRP, and were either treated with N-acetyl-L-cysteine (NAC) and or placebo. Wound healing and re-epithelialization were analyzed histopathologically in both groups, in addition to macrophage polarization, oxidative stress levels and MAPK pathway-related proteins expressions. Intracellular ROS levels were significantly increased in the prostate epithelial and stromal cells following co-culture with M1-like macrophages and H2O2 exposure via MAPK activation, which affected their proliferation, migration and apoptosis, and delayed the wound healing process. The cellular functions and wound healing capacity of the prostate cells were restored by blocking or clearing the macrophage-secreted ROS. In the beagle model, increased ROS levels impaired cellular functions, and appropriate removing ROS accelerated the wound healing process.

Maternal exposure to di-n-butyl phthalate promotes Snail1-mediated epithelial-mesenchymal transition of renal tubular epithelial cells via upregulation of TGF-ß1 during renal fibrosis in rat offspring.

We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) resulted in renal fibrosis in male offspring; however, the underlying mechanism governing this effect has not been thoroughly elucidated to date. We hypothesized that DBP exposure induces TGF-ß expression and abnormal activation of epithelial-mesenchymal transition (EMT) in fibrotic kidneys. Pregnant rats received DBP orally at a dose of 850 mg/kg BW/day during gestational days 14-18. In the DBP-exposed group, immunohistochemistry (IHC) staining showed increased expression of TGF-ß1 and EMT markers. In rat kidney tubular epithelial cells (NRK52E), ROS production increased expression levels of TGF-ß1 and subsequently contributed to the induction of Snail1-mediated EMT. Notably, DBP exposure also promoted autophagy that downregulated TGF-ß1. Taken together, our findings suggest that maternal exposure to DBP promotes EMT in tubular epithelial cells via upregulation of TGF-ß1.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

Androgen Deprivation Accelerates the Prostatic Urethra Wound Healing After Thulium Laser Resection of the Prostate by Promoting Re-Epithelialization and Regulating the Macrophage Polarization.

BACKGROUND: Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. METHODS: Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. RESULTS: The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. CONCLUSION: Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc.

Long non-coding RNA lnc-MX1-1 is associated with poor clinical features and promotes cellular proliferation and invasiveness in prostate cancer.

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined by real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer.

Clinical evaluation and technical features of three-dimensional laparoscopic partial nephrectomy with selective segmental artery clamping.

PURPOSE: To investigate the feasibility and effectiveness of three-dimensional laparoscopic partial nephrectomy with selective segmental artery clamping (3D-LPNSSAC) comparing with the conventional two-dimensional laparoscopic partial nephrectomy (2D-LPN). METHODS: Between November 2012 and March 2014, 90 patients with cT1 renal tumor at Shanghai General Hospital were enrolled in our study, which were randomly divided into two groups: the 3D-LPNSSAC group (n = 45) and 2D-LPN group (n = 45). The perioperative variables, including operative time, dissecting time, suturing time, blood loss, warm ischemia time (WIT), preoperative and postoperative renal functions, were recorded and analyzed. In addition, the oncological outcomes and complications were also evaluated. RESULTS: All the LPNs were performed successfully without conversion to radical nephrectomy or open surgery, only three cases were converted to total renal artery clamping during 3D-LPNSSAC. There were no significant differences in operative time and dissecting time between the groups, while the suturing time was shorter during 3D-LPNSSAC (P < 0.01). The technique was associated with higher blood loss (P < 0.01). The technique of 3D-LPNSSAC significantly reduced WIT (P = 0.04), and better postoperative ipsilateral renal function could be obtained during 3D-LPNSSAC (P < 0.01). During a mean follow-up time of 16.8 months (range 5.5-22.5 months), the complication rate was 8.8 % (8/90) and no tumor reoccurrence was detected. CONCLUSIONS: 3D-LPNSSAC is a feasible and safe technique for treating selective renal tumors, presenting with the beneficial clinical outcomes of reduced suturing time, shorter WIT and better postoperative ipsilateral renal function.

Comparison of the clinical efficacy and safety of retroperitoneal laparoscopic ureterolithotomy and ureteroscopic holmium laser lithotripsy in the treatment of obstructive upper ureteral calculi with concurrent urinary tract infections.

The aim of this study is to compare the clinical efficacy and safety of retroperitoneal laparoscopic ureterolithotomy (RPLU) and ureteroscopic holmium laser lithotripsy (UHLL) as two minimally invasive procedures in managing obstructive upper ureteral calculi with concurrent urinary tract infections (UTI). The retrospective study included 189 patients who underwent unilateral obstructive upper ureteral stones with concurrent UTI from January 2007 to November 2014 at our institution. Patients received RPLU (81 cases) or UHLL (108 cases). All patients received preoperative anti-infection treatment (indwelling ureteral stent and/or preoperative antibiotics). Collected data, including sex, age, stone size, success rate, operation duration, post-operation hospitalization time, and post-operation complications, were compared. All patients were followed up for more than 6 months after surgeries, and no ureterostenosis occurred. The study included 189 patients, 41 (21.7 %) females and 148 (78.3 %) males with a medium age of 52 years (range 22-81 years). All surgeries were successfully performed without conversion to open surgery. Stone size in the RPLU group was larger than that of the UHLL group (16.1 ± 1.4 vs. 10.4 ± 1.6 mm, P = 0.012). Operative duration (P = 0.009) and hospitalization time (P < 0.001) in the UHLL group were significantly shorter than those in the RPLU group, whereas stone clearance rate was significantly higher in the RPLU group (100 vs. 88.9 %, P = 0.002). Of note, postoperative fever was more common in patients treated with UHLL (15 cases) versus RPLU (4 cases) (13.9 vs. 4.9 %, P = 0.043). Moreover, in the UHLL group, three patients without a preoperative indwelling ureteral stent were complicated with sepsis, which was not seen in RPLU group. In our study, the safety and stone clearance rate of RPLU are better than those of UHLL in the treatment of unilateral upper ureteric calculi with concurrent UTI. Preoperative antibiotics and indwelling ureteral stent may reduce the risk of postoperative infections.

Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate.

This study was the first to investigate the genetic abnormalities and structural dysplasia of anorectal malformations (ARMs) in male rats induced by di(n-butyl) phthalate (DBP). DBP was administered to timed-pregnant rats to establish the ARM rat model. The incidence of ARMs in male offspring was 39.5%. In neonatal period, decreased body weight and anogenital distance were observed. The general image and histological analysis of male offspring confirmed the presence of ARMs. Anatomical examination of the ARM male rats revealed the dysplasia in solid organs (heart-lung, liver, spleen, and kidney). The decreases of serum testosterone concentration and androgen receptor expression in terminal rectum were indicative of the antiandrogenic effects of DBP. Moreover, significant decreased mRNA expressions of these androgen-related genes such as sonic hedgehog, Gli2, Gli3, bone morphogenetic protein 4, Wnt5a, Hoxa13, Hoxd13, fibroblast growth factor 10, and fibroblast growth factor receptor 2 were found in terminal rectum of the ARM male pubs. These results demonstrated that development of ARM rats was impaired by maternal exposure to DBP. The antiandrogenic effects of DBP disturbing the androgen-related signaling networks might play an important role in the occurrence of ARMs.

Urgent percutaneous nephrolithotomy for acute kidney injury secondary to bilateral stones: is it safe and effective in infants?

PURPOSE: To evaluate the efficacy and safety of urgent percutaneous nephrolithotomy (PNL) for acute kidney injury secondary to bilateral upper urinary stones in infants. METHODS: A total of seven infants (five boys and two girls), aged from 5 to 12 months, underwent urgent PNL for calculus anuria from September 2011 to March 2013. The initial blood test revealed acute renal injury in all infants. After correcting electrolyte imbalance and acid-base status through medical treatment in a short time without dialysis, all urgent PNL procedures were performed with 16F percutaneous access and small-diameter nephroscopes designed specifically for pediatric surgery on the side with the more dilated pelvis. Stones were fragmented with a pneumatic lithotripter. RESULTS: Stones were completely removed from the operative side kidneys. The operating time ranged from 35 to 57 min. Blood BUN, serum creatinine, and electrolyte levels returned to normal on postoperative 36 h. There were no major perioperative or postoperative complications and deaths. CONCLUSIONS: When performed by experienced endourologists, urgent PNL is a safe and effective procedure in infants for acute kidney injury secondary to bilateral upper urinary stones.

Two-micron thulium laser resection of the distal ureter and bladder cuff during nephroureterectomy for upper urinary tract urothelial carcinoma.

The thulium laser (Tm-laser) technique has been used in the management of many urologic conditions. The present study aimed to evaluate the use of this technique for distal ureter and bladder cuff (DUBC) excision during nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). Fifty-eight patients with UUT-UC who underwent radical nephroureterectomy were included in this retrospective study. DUBC was managed by open excision in 24 cases, by transurethral electrosurgery in 17 cases, and by transurethral Tm-laser in 17 cases. Perioperative measures and oncologic outcomes were compared among the three groups. Furthermore, 11 human ureteral segments were collected to measure the burst pressure and show physical pressure tolerance, and six ureteral segments were assessed histologically to investigate the sealing effect. Operative time and hospital stay were significantly longer, and intraoperative blood loss was significantly greater in the open excision group than in the electrosurgery and Tm-laser groups (P < 0.05 for all). There were no significant differences in these parameters between the electrosurgery and Tm-laser groups. In addition, there were no significant differences in the incidences of bladder tumors and retroperitoneal recurrence of urothelial carcinoma among the three groups. The coagulation time and resection time were significantly shorter in the Tm-laser group than in the electrosurgery group. The mean burst pressure did not differ significantly between the tissues sealed by electrosurgery and by Tm-laser. Histopathological analyses showed that distal ureters were completely sealed by both electrosurgery and Tm-laser. The Tm-laser technique is superior to open excision and comparable to transurethral electrosurgery in the management of DUBC during nephroureterectomy for UUT-UC, offering an alternative treatment option for this condition.

Two-micrometer thulium laser resection of the prostate-tangerine technique for patients with acute urinary retention.

Two-micrometer thulium laser resection of the prostate-tangerine technique (TmLRP-TT) has been introduced as a minimally invasive treatment for benign prostatic hyperplasia (BPH). Acute urinary retention (AUR) is a common and serious complication of BPH. The study was undertaken to assess the clinical efficacy and safety of TmLRP-TT in the treatment of patients with AUR secondary to BPH. A prospective evaluation of 52 patients undergoing TmLRP-TT from December 2011 to November 2012 was carried out. Preoperative status, surgical details, and perioperative complications were recorded. The follow-up outcome was evaluated with subjective and objective tests at 1 and 6 months. Mean age was 70.3 ± 7.8 years old. Mean prostate volume was 69.6 ± 31.6 ml, and mean residual volume with retention was 274.5 ± 150.7 ml. Mean operative time was 64.1 ± 30.4 min. Mean catheterization duration was 5.4 ± 1.1 days. The mean International Prostate Symptom Score, quality of life score, and postvoid residual urine volume decreased significantly at 6-month follow-up (21.6 ± 6.8 vs. 6.8 ± 3.2, 4.4 ± 1.2 vs. 0.9 ± 0.8, 274.5 ± 150.7 vs. 40.6 ± 22.5 ml). The mean maximum urinary flow rate was 18.7 ± 6.9 ml/s postoperative. Two (3.8 %) of the patients required blood transfusion in operation. Five (9.6 %) of the patients had transient hematuria postoperative, and two (3.8 %) of them received 3 days recatheterization due to clot retention. The early clinical results suggest that the TmLRP-TT is a promising safe, effective, and minimally invasive treatment for patients with AUR secondary to BPH. The incidence of complications was low.