The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells.

BACKGROUND: High levels of the post-translational modification O-GlcNAcylation (O-GlcNAc) are found in multiple cancers, including bladder cancer. Autophagy, which can be induced by stress from post-translational modifications, plays a critical role in maintaining cellular homeostasis and regulating tumorigenesis. The impact of O-GlcNAcylation on autophagy in bladder cancer remains unclear. Here, we evaluate the change in autophagic activity in response to O-GlcNAcylation and explore the potential mechanisms. METHODS: O-GlcNAcylation levels in bladder cancer cells were altered through pharmacological or genetic manipulations: treating with 6-diazo-5-oxo-norleucine (DON) or thiamet-G (TG) or up- and downregulation of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Autophagy was determined using fluorescence microscopy and western blotting. Co-immunoprecipitation (Co-IP) assays were performed to evaluate whether the autophagy regulator AMP-activated protein kinase (AMPK) was O-GlcNAc modified. RESULTS: Cellular autophagic flux was strikingly enhanced as a result of O-GlcNAcylation suppression, whereas it decreased at high O-GlcNAcylation levels. Phosphorylation of AMPK increased after the suppression of O-GlcNAcylation. We found that O-GlcNAcylation of AMPK suppressed the activity of this regulator, thereby inhibiting ULK1 activity and autophagy. CONCLUSION: We characterized a new function of O-GlcNAcylation in the suppression of autophagy via regulation of AMPK. GRAPHICAL ABSTRACT: Blockage of O-linked GlcNAcylation induces AMPK dependent autophagy in bladder cancer cells.

The clinical study of en bloc transurethral resection with 980 nm laser for treatment of primary non-muscle invasive bladder cancer.

OBJECTIVE: To elevate safety and efficacy of en bloc transurethral resection with 980 nm laser as treatment for primary non-muscle-invasive bladder cancer (NMIBC). METHODS: Total 84 cases were enrolled in this study. Among them, 36 and 48 cases underwent treatment using the 980 nm laser and the traditional TUR-BT procedure, respectively. The peri-operative characteristics (tumor size, tumor multiplicity, tumor grade, etc.) and intra-operative complications (obturator nerve reflex, bladder perforation, bladder irrigation, etc.) were recorded and compared between the two groups. RESULTS: There are no significant difference in baseline characteristics between laser and TUR-Bt treatment groups. Operation time also has no significant difference in two groups. Obturator nerve reflex and bladder perforation were noted in 6 patients and in 3 patients during TUR-Bt group, respectively. No obturator nerve reflex and bladder perforation were observed in the laser group. The patients who need bladder irrigation was lower in laser group than in TUR-Bt group. There were no significant differences in catheterization time and hospitalization time between two groups. No significant difference in the overall recurrence rate were observed among the two groups during the follow-up periods. CONCLUSION: En bloc transurethral resection using 980 nm laser is an effective and safe treatment option for non-muscle-invasive bladder cancer. Compared to the traditional TUR-Bt procedure, the procedure using 980 nm laser has fewer perioperative complications and similar oncological results.

Comparison of vaporization using 120-W GreenLight laser versus 2-micrometer continuous laser for treating benign prostatic hyperplasia: A 24-month follow-up study of a single center.

OBJECTIVE: To evaluate safety, efficacy, and long-term outcomes of photoselective vaporization of prostate using 120-W HPS GreenLight KTP laser and compare the results with those obtained with 2-micrometer continuous-wave (2 um CW) laser for treatment of patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: One group of 216 patients diagnosed with BPH underwent 120-W KTP laser vaporization of the prostate, while another group of 198 BPH patients underwent 2 um CW laser vaporization. The relevant pre-, peri-, and post-operative parameters were compared between the two therapy groups. Functional results in terms of improvement of International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and post-void residual (PVR) urine were assessed at 3, 6, 12, and 24 months. RESULTS: BPH was successfully treated with 120-W HPS KTP laser and 2 um CW laser in all patients. There were no significant difference between two patient groups in the baseline characteristics (such as PSA, IPSS, QoL, and Qmax). No major complications occurred intraoperatively (capsule perforation and TUR syndrome) or postoperatively (electric unbalance), and no blood transfusions were required in both groups. Average catheterization time was 1.9±1.3 days for the 120-W PVP and 2.2±1.9 days for the 2 um CW laser treatment. In addition, the hospitalization times were 3.8±1.2days (120-W PVP) and 4.8±1.5 days (2 um CW laser), respectively. The incidence of dysuria and urge incontinence was higher in the 2 um CW laser group (35/198, 24/198) than in the 120 W PVP group (15/216, 10/216). Dramatic improvement was observed in Qmax, IPSS, Qol, and PVR as compared with the respective pre-operative values. The degree of improvement during the follow-up period was comparable in both groups. No significant differences were observed in terms of re-operation rates, bladder neck stricture, and urethral stricture. CONCLUSIONS: Both 120-W HPS laser and 2 um CW laser vaporization present effective treatment options in patients with BPH, but 120-W PVP provides safer therapy with less post-operative complications within the 2-year follow-up period.

[Low-concentration hydrogen peroxide solution for continuous bladder irrigation after transurethral resection of the prostate].

OBJECTIVE: To evaluate the effectiveness and safety of low-concentration hydrogen peroxide solution (HPS) for continuous bladder irrigation after transurethral resection of the prostate (TURP). METHODS: We retrospectively analyzed the clinical data about 148 cases of benign prostatic hyperplasia (BPH) treated by TURP from January 2013 to January 2016. Seventy-six of the patients received postoperative continuous bladder irrigation with 0.15% HPS (group A) and the other 72 with normal saline (group B). We compared the two groups of patients in their postoperative hemoglobin (Hb) levels, duration of bladder irrigation, frequency of catheter blockage, time of catheterization, and length of hospital stay. RESULTS: There were no statistically significant differences between the two groups of patients preoperatively in the prostate volume, International Prostate Symptoms Score, maximum urinary flow rate, postvoid residual urine, or levels of serum PSA and Hb (P > 0.05). At 48 hours after operation, a significantly less reduction was observed in the Hb level in group A than in group B (ï¼»3.38 ± 2.56ï¼½ vs ï¼»7.29 ± 6.58ï¼½ g/L, P < 0.01). The patients of group A, in comparison with those of group B, also showed remarkably shorter duration of postoperative bladder irrigation (ï¼»32.57 ± 5.99ï¼½ vs ï¼»46.10 ± 8.79ï¼½ h, P < 0.01), lower rate of catheter blockage (3.3% vs 11.8%, P < 0.01), shorter time of catheterization (ï¼»3.74 ± 0.79ï¼½ vs ï¼»4.79 ± 0.93ï¼½ d, P < 0.01), and fewer days of postoperative hospital stay (ï¼»4.22 ± 0.81ï¼½ vs ï¼»4.67 ± 0.88ï¼½ d, P < 0.01). CONCLUSIONS: Low-concentration HPS for continuous bladder irrigation after TURP can reduce blood loss, catheter blockage, bladder irrigation duration, catheterization time, and hospital stay, and therefore deserves a wide clinical application.

p46Shc Inhibits Thiolase and Lipid Oxidation in Mitochondria.

Although the p46Shc isoform has been known to be mitochondrially localized for 11 years, its function in mitochondria has been a mystery. We confirmed p46Shc to be mitochondrially localized and showed that the major mitochondrial partner of p46Shc is the lipid oxidation enzyme 3-ketoacylCoA thiolase ACAA2, to which p46Shc binds directly and with a strong affinity. Increasing p46Shc expression inhibits, and decreasing p46Shc stimulates enzymatic activity of thiolase in vitro Thus, we suggest p46Shc to be a negative mitochondrial thiolase activity regulator, and reduction of p46Shc expression activates thiolase. This is the first demonstration of a protein that directly binds and controls thiolase activity. Thiolase was thought previously only to be regulated by metabolite balance and steady-state flux control. Thiolase is the last enzyme of the mitochondrial fatty acid beta-oxidation spiral, and thus is important for energy metabolism. Mice with reduction of p46Shc are lean, resist obesity, have higher lipid oxidation capacity, and increased thiolase activity. The thiolase-p46Shc connection shown here in vitro and in organello may be an important underlying mechanism explaining the metabolic phenotype of Shc-depleted mice in vivo.

High expression of Rab25 contributes to malignant phenotypes and biochemical recurrence in patients with prostate cancer after radical prostatectomy.

BACKGROUND: Ras-related protein 25 (Rab25) functions either as an oncogene or a tumor suppressor with a cancer type-dependent manner. We aimed to investigate clinical significance of Rab25 in prostate cancer (PCa). METHODS: Quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were respectively performed to detect Rab25 mRNA and protein expression in PCa and adjacent non-cancerous prostate tissues. Receiver-operating characteristic curve analysis was used to evaluate predictive diagnostic value of Rab25. Associations of Rab25 expression with various clinicopathological characteristics and biochemical recurrence-free survival of PCa patients were statistically evaluated. In vitro, PCa cell proliferation was assessed by CCK-8 assay, and the cell migration and invasion activities were evaluated by Transwell assay, following the transfection of Rab25 small interfering RNA. RESULTS: Ras-related protein 25 mRNA and protein expression in PCa tissues were both significantly higher than adjacent non-cancerous prostate tissues (both P < 0.001). The area under the curve of Rab25 immunoreactive score (IRS) was 0.896 (P < 0.001) with 74.0% sensitivity and 95.0% specificity. High Rab25 IRS was significantly associated with high Gleason score (P = 0.02) and distant metastasis (P = 0.01). PCa patients with high Rab25 IRS had shorter overall and biochemical recurrence-free survivals than those with low Rab25 IRS (both P < 0.001). Cox regression analysis identified Rab25 as an independent biomarker for both overall and biochemical recurrence-free survivals of PCa patients. By exploring its activities in vitro, Rab25 downregulation was found to inhibit PCa cell proliferation, migration and invasion. CONCLUSIONS: High expression of Rab25 may contribute to malignant progression and biochemical recurrence of PCa patients after radical prostatectomy.

The efficacy and safety of 2-µm continuous laser in the treatment of high-risk patients with benign prostatic hyperplasia.

Two-micrometer laser resection of prostate-tangerine technique dissects whole prostatic lobes off the surgical capsular, similar to peeling a tangerine. The present study aimed to evaluate the safety and efficacy of 2-µm continuous laser vaporization in the treatment of high-risk patients with benign prostatic hyperplasia (BPH) during the 24-month follow-up. The study included 248 patients with moderate to severe lower urinary tract symptoms who underwent 2-µm continuous laser vaporization of the prostate. All patients were accompanied with different degree comorbidities and 94 patients were taking oral anticoagulants. BPH was successfully treated with 2-µm continuous laser vaporization in all patients. Mean pre-operative prostate volume was 76 ± 25.3 ml and mean operative time was 49.8 ± 16.5 min. There were no major complications intra-operatively or postoperatively, and no blood transfusions were needed. About 20 patients (8.1%) needed bladder irrigation postoperatively. Average catheterization time was 2.0 ± 1.8 days (range 1-5 days). Four patients required reoperation due to enlarged prostates from residual adenoma. At 3-, 6-, 12-, and 24-month follow-ups, maximum urinary flow rates (Qmax) increased from 6.9 ± 1.7 to 19.1 ± 4.2, 19.5 ± 4.6, 19.4 ± 4.6, and 19.5 ± 4.1 ml/s, respectively. Mean International Prostate Symptom Scores (IPSS) decreased from 27.6 ± 5.1 (pre-operation) to 9.2 ± 2.6, 7.12 ± 1.42, 6.18 ± 1.32, and 6.25 ± 1.30 at 3-, 6-, 12-, and 24-month post-operation, respectively. Two-micrometer continuous laser vaporization is a safe and effective surgical endoscopic technique associated with low complication rate in BPH patients at high risk and those on anticoagulation therapy who have severe LUTS caused by BPH.

Photoselective vaporization of the prostate with GreenLight 120-W laser versus transurethral resection of the prostate for benign prostatic hyperplasia: a systematic review with meta-analysis of randomized controlled trials.

The aim of this study is to assess the overall efficacy and safety of photoselective vaporization of the prostate (PVP) with GreenLight 120-W laser versus transurethral resection of the prostate (TURP) for treating patients of benign prostate hyperplasia (BPH) with lower urinary tract symptoms (LUTS). We performed a literature search of The Cochrane Library and the electronic databases, including Embase, Medline, and Web of Science. Manual searches were conducted of the conference proceedings, including European Association of Urology and American Urological Association (2007 to 2012). Outcomes reviewed included clinical baseline characteristics, perioperative data, complications, and postoperative functional results, such as postvoid residual (PVR), international prostate symptom score (IPSS), quality of life (QoL), and maximum flow rate (Qmax). Six randomized controlled trials (RCTs) were enrolled. Three hundred and forty-seven patients undergone 120-W PVP, and 350 patients were treated with TURP in the RCTs. There were no significant differences for clinical characteristics in these trials. In perioperative data, catheterization time and length of hospital stay were shorter in the PVP group. However, the operation time was shorter in the TURP group. Capsular perforation, blood transfusion, clot retention, and macroscopic hematuria were markedly less likely in PVP-treated subjects. The other complications between PVP and TURP did not demonstrate a statistic difference. There were no significant differences in QoL, PVR, IPSS, and Qmax in the 1, 3, 6, 12, and 24 months of postoperative follow-up. There was no significant difference at postoperation follow-up of functional outcomes including IPSS, PVR, Qmax, and QoL between the TURP-treated subjects and PVP-treated subjects. Owing to a shorter catheterization time, reduced hospital duration and less complication, PVP could be used as an alternative and a promising minimal invasive surgical procedure for the treatment of BPH.

Abiraterone acetate for metastatic castration-resistant prostate cancer after docetaxel failure: A randomized, double-blind, placebo-controlled phase 3 bridging study.

OBJECTIVES: To evaluate the efficacy and safety of abiraterone acetate-prednisone versus placebo-prednisone in Asian metastatic castration-resistant prostate cancer patients who have failed docetaxel-based chemotherapy. METHODS: In this double-blind, phase 3 study from China, 214 patients were randomized (2:1) to abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily and placebo plus prednisone 5 mg twice daily in 28-day treatment cycles. RESULTS: Abiraterone acetate-prednisone treatment significantly decreased prostate-specific antigen progression risk by 49%, with longer median time to prostate-specific antigen progression of 5.55 months versus 2.76 months in the placebo-prednisone group (hazard ratio 0.506, P = 0.0001, primary end-point). There was a strong trend for improved overall survival in the abiraterone acetate-prednisone group, with a 40% decrease in the risk of death (hazard ratio 0.604, P = 0.0597); however, median survival was not reached in either group because of the short follow-up period (12.9 months) and limited number of observed death events. The prostate-specific antigen response rate was higher in the abiraterone-prednisone group (49.7%) than in the placebo-prednisone group (14.1%). A total of 37.1% patients in this group had pain progression events compared with 50.7% in the placebo-prednisone group. Abiraterone-prednisone significantly decreased the risk of pain progression by 50% (hazard ratio 0.496, P = 0.0014). The incidence of adverse events was similar between the two groups; the most common adverse events being anemia (25.9% for abiraterone-prednisone vs 22.5% for placebo-prednisone), hypokalemia (25.9% and 11.3%), bone pain (23.8% and 21.1%), hypertension (16.1% and 12.7%) and increased aspartate aminotransferase (14.7% and 15.5%), respectively. CONCLUSIONS: Abiraterone-prednisone significantly delays disease and pain progression, and prostate-specific antigen, with a favorable benefit-risk ratio in Asian metastatic castration-resistant prostate cancer patients in the post-docetaxel setting.

Application of transrectal ultrasound-guided repeat needle biopsy in the diagnosis of prostate cancer in Chinese population: A retrospective study.

BACKGROUND: Transrectal ultrasound-guided repeat needle biopsy (TUGRNB) is widely used for diagnosis of prostate cancer (PCa). However, significance of TUGRNB in Chinese population was rarely reported. A retrospective study was conducted to evaluate the significance of TUGRNB applied in prediction of PCa in Chinese population. MATERIALS AND METHODS: A total of 960 from January 2009 to December 2012 were included. Repeat needle biopsy rate and PCa positive detection rate were evaluated. Relationship between prostate specific antigen (PSA) levels and PCa positive rates was analyzed. RESULTS: PCa positive detection rate after initial needle biopsy was 28.4%, which was lower than the rate of repeat needle biopsy (40%). The rate for immediate transurethral resection (TUR), surgery after initial needle biopsy, was 27.1%, however with a low PCa positive detection rate (0.66%). The repeat needle biopsy rate was lower compared with the initial biopsy rate (P < 0.05). Meanwhile, immediate TUR rate was significantly higher than that of the repeat needle biopsy rate (P < 0.05). Among the three groups, the PCa positive detection rate in repeat needle biopsy group was the highest. In subgroups with different PSA levels, the PCa positive rate increased with the elevation of PSA level. In cases with PSA > 20 ng/ml, PCa positive rate was significantly higher than those with PSA < 20 ng/ml (P < 0.05). CONCLUSION: PCa positive detection rate following repeat needle biopsy in Chinese population was higher, although the repeated needle biopsy rate was still in a low level. TUGRNB should attract more attention in the diagnosis of PCa.

MIR106B and MIR93 prevent removal of bacteria from epithelial cells by disrupting ATG16L1-mediated autophagy.

BACKGROUND & AIMS: Variants in genes that regulate autophagy have been associated with Crohn's disease (CD). Defects in autophagy-mediated removal of pathogenic microbes could contribute to the pathogenesis of CD. We investigated the role of the microRNAs (miRs) MIR106B and MIR93 in induction of autophagy and bacterial clearance in human cell lines and the correlation between MIR106B and autophagy-related gene 16L1 (ATG16L1) expression in tissues from patients with CD. METHODS: We studied the ability of MIR106B and MIR93 to regulate ATG transcripts in human cancer cell lines (HCT116, SW480, HeLa, and U2OS) using luciferase report assays and bioinformatics analyses; MIR106B and MIR93 mimics and antagonists were transfected into cells to modify levels of miRs. Cells were infected with LF82, a CD-associated adherent-invasive strain of Escherichia coli, and monitored by confocal microscopy and for colony-forming units. Colon tissues from 41 healthy subjects (controls), 22 patients with active CD, 16 patients with inactive CD, and 7 patients with chronic inflammation were assessed for levels of MIR106B and ATG16L1 by in situ hybridization and immunohistochemistry. RESULTS: Silencing Dicer1, an essential processor of miRs, increased levels of ATG protein and formation of autophagosomes in cells, indicating that miRs regulate autophagy. Luciferase reporter assays indicated that MIR106B and MIR93 targeted ATG16L1 messenger RNA. MIR106B and MIR93 reduced levels of ATG16L1 and autophagy; these increased after expression of ectopic ATG16L1. In contrast, MIR106B and MIR93 antagonists increased formation of autophagosomes. Levels of MIR106B were increased in intestinal epithelia from patients with active CD, whereas levels of ATG16L1 were reduced compared with controls. Levels of c-Myc were also increased in intestinal epithelia of patients with active CD compared with controls. These alterations could impair removal of CD-associated bacteria by autophagy. CONCLUSIONS: In human cell lines, MIR106B and MIR93 reduce levels of ATG16L1 and autophagy and prevent autophagy-dependent eradication of intracellular bacteria. This process also appears to be altered in colon tissues from patients with active CD.

MiRNA-30a-mediated autophagy inhibition sensitizes renal cell carcinoma cells to sorafenib.

Chemotherapy-induced autophagy activation often contributes to cancer resistance. MiRNA-30a (miR-30a) is a potent inhibitor of autophagy by downregulating Beclin-1. In this study, we characterized the role of miR-30a in sorafenib-induced activity in renal cell carcinoma (RCC) cells. We found that expression of miR-30a was significantly downregulated in several human RCC tissues and in RCC cell lines. Accordingly, its targeted gene Beclin-1 was upregulated. Sorafenib activated autophagy in RCC cells (786-0 and A489 lines), evidenced by p62 degradation, Beclin-1/autophagy protein 5 (ATG-5) upregulation and light chain (LC)3B-I/-II conversion. Exogenously expressing miR-30a in 786-0 or A489 cells inhibited Beclin-1 expression and enhanced sorafenib-induced cytotoxicity. In contrast, knockdown of miR-30a by introducing antagomiR-30a increased Beclin-1 expression, and inhibited sorafenib-induced cytotoxicity against RCC cells. Autophagy inhibitors, including chloroquine, 3-methyaldenine or Bafliomycin A1, enhanced sorafenib activity, causing substantial cell apoptosis. Meanwhile, knockdown of Beclin-1 or ATG-5 by targeted siRNAs also increased sorafenib-induced cytotoxicity in above RCC cells. These findings indicate that dysregulation of miR-30a in RCC may interfere with the effectiveness of sorafenib-mediated apoptosis by an autophagy-dependent pathway, thus representing a novel potential therapeutic target for RCC.

Oncolytic virus carrying shRNA targeting SATB1 inhibits prostate cancer growth and metastasis.

Recent studies suggest that SATB1 is a promising therapeutic target for prostate cancer. To develop novel SATB1-based therapeutic agents for prostate cancer, in this study, we aimed to construct ZD55-SATB1, an oncolytic adenovirus ZD55 carrying shRNA targeting SATB1, and investigate its effects on the inhibition of prostate cancer growth and metastasis. ZD55-SATB1 was constructed and used to infect human prostate cancer cell lines DU145 and LNCaP. The inhibitory effect of ZD55-SATB1 on SATB1 expression was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The cytotoxicity of ZD55-SATB1 was detected by MTT assay. Cell invasion was detected by Matrigel invasion assay. The in vivo antitumor activities of ZD55-SATB1 were evaluated in xenograft mouse model. We found that ZD55-SATB1 selectively replicated and significantly reduced SATB1 expression in DU145 and LNCaP cells. ZD55-SATB1 effectively inhibited the viability and invasion of DU145 and LNCaP cells in vitro and inhibited prostate cancer growth and metastasis in xenograft nude mice. In conclusion, replicative oncolytic adenovirus armed with SATB1 shRNA exhibits effective antitumor effect in human prostate cancer. Our study provides the basis for the development of ZD55-SATB1 for the treatment of prostate cancer.

Changing trends in the causes and management of male urethral stricture disease in China: an observational descriptive study from 13 centres.

OBJECTIVE: To determine whether there have been any changes in the causes and management of urethral strictures in China. PATIENTS AND METHODS: The data from 4,764 men with urethral stricture disease who underwent treatment at 13 medical centres in China between 2005 and 2010 were retrospectively collected. The databases were analysed for the possible causes, site and treatment techniques for the urethral stricture, as well as for changes in the causes and management of urethral strictures. RESULTS: The most common cause of urethral strictures was trauma, which occurred in 2,466 patients (51.76%). The second most common cause was iatrogenic injures, which occurred in 1,643 patients (34.49%). The most common techniques to treat urethral strictures were endourological surgery (1,740, 36.52%), anastomotic urethroplasty (1,498, 31.44%) and substitution urethroplasty (1,039, 21.81%). A comparison between the first 3 years and the last 3 years showed that the constituent ratio of endourological surgery decreased from 54% to 32.75%, whereas the constituent ratios of anastomotic urethroplasty and substitution urethroplasty increased from 26.73% and 19.18% to 39.93% and 27.32%, respectively (P < 0.05). CONCLUSIONS: During recent years, there has been an increase in the incidence of urethral strictures caused by trauma and iatrogenic injury. Endourological urethral surgery rates decreased significantly, and open urethroplasty rates increased significantly during the last 3 years.

[Extracorporeal shock wave: An effective and safe therapy for the pain symptom of type IIIB prostatitis].

OBJECTIVE: To investigate the effect and safety of extracorporeal shock wave (ESW) in the treatment of pain symptom of type III B prostatitis. METHODS: We treated 50 cases of type III B prostatitis by ESW once a week for 4 weeks. Then we evaluated the clinical effect and safety of the therapy based on the NIH-CPSI scores, visual analogue scale (VAS) scores, IIEF-5 scores, prostate volume and morphous, state of urination, color of urine, results of routine semen analysis, and changes of cytokines (IL-6, TNF-α and IL-1ß) in expressed prostatic secretion (EPS). RESULTS: All the patients successfully accomplished the treatment. Compared with the baseline, decreases were observed after 4 weeks of cytokine treatment in the pain scores (14. 61 ± 1. 82 vs 9. 36 ± 1. 47, P <0. 01), urination symptom scores (4. 59 ± 1. 01 vs.4. 66 ± 0. 89, P >0. 05) , quality of life scores (6. 51 ± 1. 03 vs 4. 56 ± 1. 02, P <0. 01), NIH-CPSI (25. 43 ± 1. 72 vs 18. 28 ± 2. 32, P <0. 01 ), and VAS (6. 59 ± 1. 10 vs 3. 02 ± 1. 07, P < 0. 01). The concentration of IL-6 in the EPS was significantly increased ([55.82 ± 6. 28] vs [86.59 ± 4. 55] ng/ml, P <0. 01) , while the level of TNF-α ([3.89 ± 0. 12] vs [3. 19 ± 0.22] ng/ml, P<0.01) and that of IL-1ß ([3.21 ± 1.01] vs [1.48 ± 0.95] ng/ml, P< 0. 01) remarkably reduced after treatment. However, there were no statistically significant differences in IIEF-5 scores (18. 58 ± 2. 03 vs 18. 51 1. 89, P >0. 05) or various sperm parameters before and after treatment (P >0. 05). And no significant changes were observed in the prostate volume, morphous or internal echoes. CONCLUSION: The ESW therapy is effective and safe for the pain symptom of type III B prostatitis.

Increased chemosensitivity via targeting testicular nuclear receptor 4 (TR4)-Oct4-interleukin 1 receptor antagonist (IL1Ra) axis in prostate cancer CD133+ stem/progenitor cells to battle prostate cancer.

Prostate cancer (PCa) stem/progenitor cells are known to have higher chemoresistance than non-stem/progenitor cells, but the underlying molecular mechanism remains unclear. We found the expression of testicular nuclear receptor 4 (TR4) is significantly higher in PCa CD133(+) stem/progenitor cells compared with CD133(-) non-stem/progenitor cells. Knockdown of TR4 levels in the established PCa stem/progenitor cells and the CD133(+) population of the C4-2 PCa cell line with lentiviral TR4 siRNA led to increased drug sensitivity to the two commonly used chemotherapeutic drugs, docetaxel and etoposide, judging from significantly reduced IC50 values and increased apoptosis in the TR4 knockdown cells. Mechanism dissection studies found that suppression of TR4 in these stem/progenitor cells led to down-regulation of Oct4 expression, which, in turn, down-regulated the IL-1 receptor antagonist (IL1Ra) expression. Neutralization experiments via adding these molecules into the TR4 knockdown PCa stem/progenitor cells reversed the chemoresistance, suggesting that the TR4-Oct4-IL1Ra axis may play a critical role in the development of chemoresistance in the PCa stem/progenitor cells. Together, these studies suggest that targeting TR4 may alter chemoresistance of PCa stem/progenitor cells, and this finding provides the possibility of targeting TR4 as a new and better approach to overcome the chemoresistance problem in PCa therapeutics.

HSC20 interacts with frataxin and is involved in iron-sulfur cluster biogenesis and iron homeostasis.

Friedreich's ataxia is a neurodegenerative disorder caused by mutations in the frataxin gene that produces a predominantly mitochondrial protein whose primary function appears to be mitochondrial iron-sulfur cluster (ISC) biosynthesis. Previously we demonstrated that frataxin interacts with multiple components of the mammalian ISC assembly machinery. Here we demonstrate that frataxin interacts with the mammalian mitochondrial chaperone HSC20. We show that this interaction is iron-dependent. We also show that like frataxin, HSC20 interacts with multiple proteins involved in ISC biogenesis including the ISCU/Nfs1 ISC biogenesis complex and the GRP75 ISC chaperone. Furthermore, knockdown of HSC20 caused functional defects in activity of mitochondrial ISC-containing enzymes and also defects in ISC protein expression. Alterations up or down of frataxin expression caused compensatory changes in HSC20 expression inversely, as expected of two cooperating proteins operating in the same pathway and suggesting a potential therapeutic strategy for the disease. Knockdown of HSC20 altered cytosolic and mitochondrial iron pools and increased the expression of transferrin receptor 1 and iron regulatory protein 2 consistent with decreased iron bioavailability. These results indicate that HSC20 interacts with frataxin structurally and functionally and is important for ISC biogenesis and iron homeostasis in mammals. Furthermore, they suggest that HSC20 may act late in the ISC pathway as a chaperone in ISC delivery to apoproteins and that HSC20 should be included in multi-protein complex studies of mammalian ISC biogenesis.

Mutant Twinkle increases dopaminergic neurodegeneration, mtDNA deletions and modulates Parkin expression.

Parkinson's disease (PD) is the second most common neurodegenerative disorder in the developed world, and is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Somatic mitochondrial DNA (mtDNA) deletions reach their highest concentration with age in the SN in humans, and may contribute to PD; yet whether mtDNA deletions cause DA neuron degeneration remains unclear. Inherited mutations of Twinkle helicase involved in mtDNA replication causes a dominant increase in mtDNA deletions in humans. We constructed a mouse model expressing mutant Twinkle in DA neurons. Mutant mice had an increase in age-related mtDNA deletions, reduction of DA neuron number in SN at 17-22 months and displayed abnormalities in rota-rod behavior. Functional analysis of midbrain indicated a slight reduction in mitochondrial state II respiration in mutants, but no decrease in maximal respiration. Also, Parkin expression was significantly decreased in DA neurons in the SN of 22-month-old mutant mice, and in PC12 cells after 48 h transfection of mutant Twinkle. Both confocal imaging and coimmunoprecipitation indicated interaction of Twinkle with Parkin in the mitochondria. Parkin overexpression rescued the reduction of proteasome activity caused by mutant Twinkle in PC12 cells. In addition, the autophagy marker LC3 was increased in the SN of 22-month transgenics, and this increase was similarly mutant Twinkle-dependent in PC12 cells. Collectively, our data demonstrate that mammalian Twinkle is important for mitochondrial integrity in DA neurons and provide a novel mouse model in which increased mtDNA deletions may lead to DA neuron degeneration and parkinsonism.

[Inhibition of stromal interaction molecule 1 and the expression of apoptosis-related proteins in prostate cancer PC-3 cells].

OBJECTIVE: To explore the effects of stromal interaction molecule 1 (STIM1) on the expression of apoptosis-related proteins in prostate cancer PC-3 cells. METHODS: We transfected the lentivirus vector STIM1-pGCSIL-GFP carrying STIM shRNA into human hormone-independent prostate cancer PC-3 cells, and 3 days later observed the transfection efficiency by fluorescence microscopy. At 7 days after transfection, we determined the expression of STIM1 in the PC-3 cells by RT-PCR and Western blot and those of apoptosis-related proteins Bcl-2, Bax, survivin and activated Caspase-3 by Western blot. RESULTS: At 3 days, inverted microscopy revealed a transfection efficiency of > 80%. At 7 days, the STIM1 expression was significantly inhibited at both mRNA and protein levels. The Bcl-2/Bax rate was remarkably decreased as compared with that of the control group (0. 31 vs 1.24 ) , and the survivin expression was markedly reduced, 0. 14 times that of the relative expression in the control. However, the Caspase-3 cleavage was significantly activated, 1.52 times that of the control (P <0.05). CONCLUSION: STIM1 can be regarded as an oncogene in prostate cancer PC-3 cells. Inhibition of its expression can induce PC-3 cell apoptosis by reducing the Bcl-2/Bax rate, decreasing the survivin expression, and activating the Caspase-3 pathway.