Tong-Xin Yang

Efficacy of Phosphodiesterase-5 Inhibitor in Men With Premature Ejaculation: A New Systematic Review and Meta-analysis.

OBJECTIVE To clarify the efficacy of phosphodiesterase-5 inhibitor (PDE5i) in men with premature ejaculation (PE). METHODS We searched the PubMed, Embase, and Cochrane Library databases to identify all randomized controlled trials and compared results, including intravaginal ejaculation latency time, satisfaction, side effects, and others, after treatment with PDE5i vs placebo, PDE5i vs selective serotonin reuptake inhibitor (SSRI), or combined use of PDE5i with SSRI vs SSRI alone for treating PE. RESULTS The study inclusion criteria were met by 10 studies (10 randomized controlled trials with 3 crossover studies) involving 775 patients. The data synthesized from these studies indicated that the efficacy of PDE5i was better than that of placebo; however, more patients had side effects while taking PDE5i. The efficacy of PDE5i was better than that of SSRIs, and no significant difference was observed in the frequency of side effects. The efficacy of the combined treatment was significantly better than that of SSRI alone; however, more patients had side effects from the combined treatment. The major limitations of this meta-analysis were that there is no universally agreed definition of PE, and the types of medications differed among the studies evaluated. CONCLUSION PDE5i was significantly more effective than a placebo or SSRI for treating PE; however, it had more side effects than placebo. The combined treatment of PDE5i and SSRI had better efficacy but more side effects than the use of SSRI alone.

Factors Influencing Repair Outcomes of Vesicovaginal Fistula: A Retrospective Review of 139 Procedures.

Introduction: We aimed to report the outcomes of patients undergoing vesicovaginal fistula (VVF) repair to identify prognostic factors. Materials and Methods: Patients who underwent VVF repair between January 2009 and October 2015 were reviewed. Primary outcome was fistula closure at 3 months. Results: A total of 123 patients and 139 procedures of VVF repair were reviewed. The overall success rate was 85.6%. There were no significant differences in age (p = 0.476), etiology (p = 0.900), fistula duration (p = 0.491) and number of repairs (p = 0.509) between success and fail group. Moderate or severe perifistula fibrosis and multiple fistula were associated with failure in repair of fistula (70.8 vs. 93.4%, p < 0.001; 62.5 vs. 88.6%, p = 0.005). No difference was seen in success rate of vaginal and abdominal approaches (86.0 vs. 85.0%, p = 0.800). Logistic regression analysis identified fistula number (p = 0.003) and perifistula fibrosis (p = 0.002) as 2 independent prognostic factors. Medium/large fistulas were 3.2 times more likely to fail in repair than small fistulas (OR 3.2, 95% CI 0.95-10.6, p = 0.061). Conclusions: Fistula number and perifistula fibrosis were 2 independent prognostic factors for fistula repair. Unsuccessful closure was more likely in medium/large VVF.

MiR 3180-5p promotes proliferation in human bladder smooth muscle cell by targeting PODN under hydrodynamic pressure

Human bladder smooth muscle cells (HBSMCs) were subjected to pressure cycles of up to 200 cm H2O to a pressure of 0 cm H2O for 24 hours. The total RNA extracted from each group was subjected to microarray analysis. miR-3180-5p emerged as the most overexpressed of all the differentially expressed microRNAs, and this finding was validated by PCR. We then used CCK-8 to quantify cell proliferation after liposome-mediated transfection. Subsequently, we investigated the change in PODN and its downstream signaling proteins, including cyclin-dependent kinase 2 (cdk2) and p21. In addition, flow cytometry was performed to quantify cell-cycle distribution. The results show that miR-3180-5p, the microRNA that was most overexpressed in response to HP, reduced the expression of PODN and podocan (p = 0.004 and p = 0.041, respectively). Silencing of PODN via miR-3180-5p overexpression revealed a significant promotion of cell proliferation increased in the CCK-8 experiment, p = 0.00077). This cell proliferation was accompanied by an increase in cdk2 expression (p = 0.00193) and a decrease in p21 expression (p = 0.0095). The percentage of cells in (S + G2/M) improved after transfection (p = 0.002). It was apparent that HP upregulates miR-3180-5p, which inhibits the expression of PODN and promotes HBSMC proliferation via the cdk2 signaling pathway.

Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway

ObjectivesTo investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs).MethodsHBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection.ResultsThe expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK.ConclusionSimulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.

Is Urethrectomy Necessary During Cystectomy in Patients With Interstitial Cystitis or Bladder Pain Syndrome

OBJECTIVE To assess the outcome of cystectomy and cystourethrectomy in patients with intractable interstitial cystitis or bladder pain syndrome, and to identify whether urethrectomy is necessary. METHODS AND MATERIALS During 2007-2014, 18 women were eligible and elected for surgical treatment after conservative treatment failed. Seven cystectomies with ileal conduit urinary diversions, 8 cystourethrectomies with ileal conduit urinary diversions, and 3 supratrigonal cystectomy with orthotopic ileocystoplasty were performed. Patient histories, perioperative medical records, and follow-up outcomes were evaluated and summarized. RESULTS Patients reported subjectively improved social function and mental condition secondary to decreased urination frequency postoperatively. Pain also significantly decreased compared with baseline. To date, additional surgery to alleviate persistent symptoms or postoperative complications has not been necessary. Furthermore, there was no association between reported urethral pain and the initial transvaginal urethrectomy incidence (P = .326). More operation time and longer postoperative hospitalization duration were recorded without better surgical outcomes in the urethrectomy group (P values <.05). CONCLUSION Cystectomy and cystourethrectomy is effective and adequate treatment for interstitial cystitis or bladder pain syndrome, and our experience indicates that urethrectomy is not routinely needed. However, further long-term, prospective studies involving a larger study group are needed.

Combination of solifenacin and tamsulosin may provide additional beneficial effects for ureteral stent-related symptoms—outcomes from a network meta-analysis

PurposeTo systematically evaluate the different efficacy among generally used drugs for stent-related symptoms (SRS) with the method of network meta-analysis.MethodsA systematic search was performed in the US National Library of Medicine’s life science database (Medline), Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database for Systematic Reviews before December 2017. Analysis was performed under multivariate random-effects network model and effects of drugs were ranked with surface under the cumulative ranking (SUCRA) probabilities.Results19 trials with 2036 patients investigating 4 different intervention including tamsulosin (Tam), alfuzosin (Alfu), solifenacin (Soli) and combination of Tam and Solif were finally included in our analysis. Tam plus Soli had the highest SUCRA on all aspects of ureteral stent symptom questionnaire: urinary symptoms (86.2%), body pain (85.0%), general health (80.5%), work performance (72.0%) and sexual performance (84.4%). Except for pain relief, Soli showed higher SUCRA than Tam or Alfu in rest respects. Tam and Alfu showed similar SUCRA on urinary symptoms (53.0 vs 48.7%) and body pain relief (61.9 vs 62.9%).ConclusionsTam plus Soli might be the most effective intervention for SRSs. As for monotherapy, Soli showed advantages in most respects except for pain relief compared to Tam or Alfu. Tam and Alfu showed similar efficacy on urinary symptoms and body pain relief.

Long term Follow-up of Transvaginal Anatomical Implant of Mesh in Pelvic organ prolapse

Transvaginal mesh (TVM) is a minimally invasive but effective treatment for pelvic organ prolapse (POP). However, mesh exposure is a common and problematic complication after TVM. This study assessed the safety and long-term outcomes of TVM. A retrospective review was performed on the medical records of 175 consecutive patients who underwent TVM with the anatomical implant technique for pelvic organ prolapse at our center from April 2007 to December 2012. All operations were performed using TVM with the anatomical implant technique. Intraoperative variables, postoperative complications, and TVM outcomes were assessed. In average of 8 years (ranging from 4 to 10 years), the objective cure ratio reached 99.4%; and the subjective success rate of the TVM operation was 91.4%. Only 2 cases (1.1%) were identified as having mesh exposure. The reoperation rate was 4.0% (95% CI, 1.1–6.9%). No patients abstained from sex due to the operation or postoperative discomfort. Our anatomical implant technique for correcting POP is feasible in TVM procedures, which lead to favourable subjective and objective outcomes with the lowest rates of mesh exposure (1.1%) in published data. Therefore, performing TVM operations with the appropriate technique could consider to be permitted.

The Antimuscarinic Agent Tolterodine Regulates Bladder Extracellular Matrix in Partial Bladder Outlet Obstruction in Rats

Background/Aims: Antimuscarinic agents can delay the progression of bladder dysfunction caused by bladder outlet obstruction (BOO). To date, the relationship between muscarinic receptor activity and the bladder extracellular matrix (ECM) remains unclear. Thus, an animal model of partial BOO (PBOO) in female rats was established to explore the variation in bladder wall ECM proteins under PBOO conditions with antimuscarinic agent administration. Methods: Rats were randomly divided into three groups: sham, PBOO, and PBOO plus tolterodine. Picrosirius red staining was used to examine the smooth muscle and collagen content of bladder samples. Gene microarray and RT-PCR were performed to survey the expression of ECM proteins, receptors, and metabolism regulators in the rat bladder. Positive results were further evaluated by immunohistochemistry. Results: Picrosirius red staining showed that smooth muscle volume significantly increased in the PBOO and PBOO plus tolterodine groups (p < 0.05), while collagen significantly increased in the PBOO group (p < 0.05) but not in the PBOO plus tolterodine group. Gene microarray and RT-PCR revealed that none of the collagen subtypes exhibited significant changes after PBOO establishment and tolterodine administration. However, matrix metalloproteinases (MMPs) increased significantly in the PBOO plus tolterodine group (p < 0.05). Additionally, PBOO inhibited the expression of non-collagen ECM proteins in the rat bladder wall, while tolterodine induced the expression of non-collagen ECM proteins and ECM receptors. Conclusions: Tolterodine decreased the volume of collagen in PBOO rat bladder wall, possibly via MMPs, and regulated the expression of ECM proteins and receptors.

A network meta-analysis on the beneficial effect of medical expulsive therapy after extracorporeal shock wave lithotripsy

We applied a newly introduced method, network meta-analysis, to re-evaluate the expulsion effect of drugs including tamsulosin, doxazosin, nifedipine, terazosin and rowatinex after extracorporeal shock wave lithotripsy (ESWL) as described in the literature. A systematic search was performed in Medline, Embase and Cochrane Library for articles published before March 2016. Twenty-six studies with 2775 patients were included. The primary outcome was the number of patients with successful stone expulsion. The data were subdivided into three groups according to duration of follow-up. A standard network model was established in each subgroup. In 15-day follow-up results, SUCRA outcome showed the ranking of effects was: doxazosin > tamsulosin > rowatinex > nifedipine > terazosin (88.6, 77.4, 58.6, 32.2 and 30.4, respectively). In 45-day follow-up results, SUCRA ranking was: tamsulosin > nifedipine > rowatinex (69.4, 67.2 and 62.6, respectively). In 90-day follow-up results, SUCRA ranking was: doxazosin > rowatinex > tamsulosin (84.1, 68.1 and 49.1, respectively). In conclusion, doxazosin and tamsulosin have potential to be the first choice for pharmacological therapy to promote the expulsion of urinary stone fragments after ESWL, with this doxazosin can improve the SFR in the long term, while tamsulosin may result more in accelerating the process of expulsion.

Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction

Background/Aims: Overactive bladder associated with bladder outlet obstruction (BOO) is a highly prevalent condition, which is usually treated with antimuscarinics. However, the potential effects of antimuscarinics on the structure and function of bladder have not been investigated thus far. Methods: Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery, and then received treatment of three different antimuscarinics (Solifenacin, Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder function and structure were measured. The effect of antimuscarinics on cellular alteration in vitro was observed under mechanical stimulation. Bladder morphology were examined by immunohistochemistry, and the bladder function were investigated by cystometry and strip contractility test. The expression of muscarinic receptors and inflammatory cytokines were measured by PCR and Western blotting. Results: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are protective regulators for the bladder structure and function. Antimuscarinics decrease the weight of bladders with BOO. Antimuscarinics improve the voiding parameter and enhance the contraction of bladder smooth muscle. The results also show that antimuscarinics inhibit the proliferation of bladder smooth muscle cells both in vivo and in vitro, it can reduce the collagen deposition and inflammatory cytokines in bladders with BOO. During this process, the expression of M2 and M3 receptors was altered by antimuscarinics. Conclusion: Antimuscarinics could reverse the structural and functional changes of BOO bladder wall at cellular and tissue level, and the alteration of M2 and M3 receptors may be involved in this biological process.