UPK3A+ umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome.

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor-like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3-NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self-repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland.

The design and evaluation of a quick checklist for urodynamic quality control: A prospective single-center small sample study.

PURPOSE: To design a quick checklist for urodynamic study (UDS), aiming to reduce the occurrence of errors in the process, which may help to increase the quality of UDS. And further to analyze the effectiveness of this quick checklist for UDS quality control. METHODS: First, a quick checklist for uroflow study and pressure-flow study was developed, based on the International Continence Society-Good Urodynamic Practice standards, our previous studies, and recent literature, as well as expert suggestions. Then, patients who underwent UDS between January 2023 to February 2023 were randomly assigned to a study group or a control group. For the study group, the quick checklist was used throughout the UDS process, while the control group did not. The main artefacts were chosen to verify the effectiveness of the quick checklist for improving the UDS quality. RESULTS: The quick checklist comprised three subtypes: checklist for patients, checklist for environment and device, and checklist for UDS test process. 38 UDS traces per group were included. The incidence of missing the standard cough test decreased significantly from 18.4% to 0 (p = 0.012), with the checklist implementation. The baseline drift frequency rate also declined significantly from 39.5% to 5.3% (p < 0.05). Volume < 150 mL on uroflow study occurred in 68.4% of cases and its frequency rate decreased significantly with checklist implementation (p < 0.05). CONCLUSION: A quick checklist for quality control of UDS was developed. The quick checklist as a convenient, quick, and easy used urodynamic quality control method, may help to reduce the technical artefacts and improve fundamental urodynamic quality control. Future research with a larger sample size is needed to confirm the effectiveness of the checklist.

Statistical process control for the analysis of quality control in urodynamics: A potential new approach for quality review of urodynamics.

PURPOSE: To analyze quality control in urodynamic studies, using a proportion control chart (p-chart) for statistical process control. MATERIALS AND METHODS: This single-center study was conducted at the Urodynamic Center of West China Hospital, Sichuan University. We randomly selected 15 samples from each month in 2020, and 180 urodynamic traces were finally enrolled. We used the p-chart of statistical process control for analysis. We calculated the proportion of the incidence of a selected set of artefacts in the monthly urodynamic study process, including non-standard zero setting, no cough test, incomplete records of all measurements by urodynamicists, catheter displacement, and baseline drift. Through the specific calculation formula of statistical process control, we obtained the values of the center line, lower control limit, and upper control limit. RESULTS: All data points of each artefact were within zone A. However, one outlier was found in the p-chart of all artefacts in October, which might have been caused by inexperienced operators. CONCLUSIONS: Statistical process control may play an important role in the process control of urodynamic studies and guide us in identifying the cause of poor quality in process management.

Correlation between obesity-related measurements and initial and initial resting intravesical and abdominal pressures in urodynamic study using air-filled catheter system.

OBJECTIVES: To establish the initial (before pressure equilibrium) and initial resting intravesical and abdominal pressure in the sitting position using air-filled catheters, to assess the correlation between these pressures and obesity-related measurements, and to estimate if obesity-related measurements can be a guide to interpret initial and initial resting pressures in urodynamic testing. METHODS: Patients with non-neurogenic lower urinary tract symptoms referred for urodynamic testing in our center were consecutively enrolled in a prospective study from August 2022 to October 2022. The correlation between the initial and initial resting pressures (before and after pressure equilibrium) and obesity-related measurements were analyzed using Pearson's correlation coefficient and multiple linear regression analysis. RESULTS: Ninety-eight patients aged 56 ± 16 were studied. The 95% range of the initial intravesical and abdominal pressure were 18-42 cmH2 O and 21-60 cmH2 O, respectively. The initial resting intravesical, abdominal, and detrusor pressure in the 95% range were 17-41, 16-42, and -5 to 4 cmH2 O, respectively. Over the multiple analysis, abdominal fat thickness, and body mass index (BMI) correlated independently with initial intravesical pressure, and only visceral fat grade correlated with initial abdominal pressure. BMI correlated independently with initial resting intravesical pressure. CONCLUSIONS: Our results determined the ranges of values of both initial and initial resting pressures in the air-charged system. Meanwhile, the present study indicated the obesity-related measurements may be used as a guide to interpret the initial and initial resting pressures in urodynamic testing, and may provide a reference for the quality control of these pressures.

Evaluation of the effectiveness of four alternative approaches for the classical cough test during a urodynamic study in the context of the COVID-19 global pandemic.

BACKGROUD: To evaluate four different alternatives to the classical cough test during a urodynamic study in the context of the COVID-19 pandemic. METHODS: Patients who needed to undergo a urodynamic study (UDS) at the West China Hospital of Sichuan University between April 2021 and May 2021 were randomly selected according to the inclusion and exclusion criteria. During the UDS process, we used four alternative methods to the "cough test": 1) quickly pressing the bladder area, 2) performing the Valsalva maneuver, 3) performing the Kegel maneuver, and 4) letting the patient close their mouth while performing the cough test. The "cough" waveform amplitudes and characteristics of the graphics were obtained and compared with the classical cough test. RESULTS: A total of 120 patients (89 men, 31 women) were included in the study. There was no significant difference between the cough waveform amplitude induced by the Valsalva maneuver compared with the classical cough test (P = 0.182); there was no significant difference between the cough waveform amplitude induced by the cough test with the mouth closed and the classical cough test (P = 0.342); there was no significant difference between pressing quickly on the bladder area and the classical method (P = 0.076); and there was a significant difference between the data obtained by the Kegel maneuver and the classical method (P < 0.05). The average "cough" amplitudes obtained were 73.14 ± 22.48 cm H2O, 66.17 ± 17.12 cm H2O, 82.93 ± 18.95 cm H2O, 26.50 ± 8.68 cm H2O, and 68.90 ± 20.32 cm H2O by the classical cough test, by quickly pressing the bladder area, by the Valsalva maneuver, by the Kegel maneuver, and by coughing with a closed mouth, respectively. CONCLUSION: Quickly pressing the bladder area, performing the Valsalva maneuver, and letting the patient close their mouth while performing the cough test can all provide effective cough waveforms and amplitudes. TRIAL REGISTRATION: No. 2021-183.

Bladder Sonomorphological Tests in Diagnosing Bladder Outlet Obstruction in Patients with Lower Urinary Tract Symptoms: A Systematic Review and Meta-Analysis.

AIMS: We aimed to investigate the accuracy of bladder sonomorphological parameters including detrusor wall thickness (DWT) and ultrasound-estimated bladder weight (UEBW) for diagnosing bladder outlet obstruction (BOO) in patients with lower urinary tract symptoms (LUTS). METHODS: A comprehensive search was conducted through databases including PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, China Knowledge Network (CNKI), China Biomedical Literature Database, Wanfang Database, the Chongqing VIP Chinese Science, and Technology Periodical Database (VIP) to select studies assessing the diagnostic accuracy of DWT and UEBW to diagnose BOO in adults with LUTS. Databases were searched from inception to 2020 without restriction. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), and measures of accuracy were calculated using random-effects model. RESULTS: The initial search included 84 publications, of which 78 publications were screened, and 16 studies with 1,847 patients finally contained diagnostic data. The results from 10 out of 16 studies assessing DWT showed a pooled sensitivity (SSY) of 0.68 (95% CI, 0.56-0.78) and specificity (SPY) of 0.91 (95% CI, 0.82-0.96) with I2 values of 93%, while 6 studies evaluating UEBW were analyzed with a SSY of 0.88 (95% CI, 0.78-0.93) and SPY of 0.81 (95% CI, 0.67-0.90) with I2 values of 83%. CONCLUSIONS: DWT shows high SPY, and UEBW performs high SSY of diagnosing BOO. Further well-designed studies are needed to evaluate the utilization of DWT and UEBW for the diagnosis of BOO.

A bibliometric analysis of top-cited journal articles in interstitial cystitis and bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: To identify and compare the top-cited articles from all indexed journals and urology-nephrology and obstetrics-gynecology journals in the Institute for Scientific Information Web of Science's Citation Index Expanded on interstitial cystitis and bladder pain syndrome (IC/BPS). METHODS: Cross-sectional bibliometric analysis of top-cited articles in Web of ScienceTM (WoS) from 1900-2022. The articles were retrieved by the MeSH terms from NCBI. The characteristics of top 100 cited articles from all indexed journals and specialized journals were evaluated. RESULTS: A total of 5547 articles were collected from 1115 journals, in which 3225 articles were from 141 urological and gynecological specialized journals. The USA and the UK were the top two origins for articles on interstitial cystitis. The articles from non-specialized journals were more frequently cited than those from specialized journals (median [IQR], 221.5 [189.8-313.5] vs 131.0 [126.0-142.8], P < 0.0001). The citation number per year showed similar results (median [IQR], 239.9 [194.5-311.8] vs 132.0 [126.7-140.5], P < 0.0001). There were many more open-access articles in non-specialized than specialized journals (P = 0.0018). CONCLUSIONS: The current study initially queried the articles published on WoS on IC/BPS by the number of citations to identify the differences between two journal categories. The characteristics and trends of research were analyzed by citations to provide insights into the current research status and future direction.

Identification of key genes in human urothelial cells corresponding to interstitial cystitis/bladder pain syndrome in a lipopolysaccharide-induced cystitis model.

AIMS: The cellular functions of bladder urothelial cells in interstitial cystitis/bladder pain syndrome (IC/BPS) have not been well revealed and understood. Thus, the study aims to identify key genes and significant pathways in urothelium corresponding to IC/BPS in a lipopolysaccharide (LPS)-induced cystitis model and provide novel clues related to diagnosis and treatment of IC/BPS. METHODS: Human urothelial cells (HUCs) were incubated with LPS (50 µg/ml for 24 h). Microarray was applied to analyze the differentially expressed genes (DEGs) between HUCs under LPS treatment and the control group. DEGs in the two groups were identified and then used for enrichment analysis. Subsequently, protein-protein interaction (PPI) network based on DEGs was constructed. Lastly, the top five key genes were identified through the Cytoscape (version 3.7.2) using the "Clustering Coefficient" algorithm. RESULTS: One hundred and seventy-one DEGs (96 upregulated genes and 75 downregulated genes) were identified between the LPS treatment and control group. The established PPI network was composed of 169 nodes and 678 edges. Moreover, C19orf33, TRIM31, MUC21, ELF3, and IFI27 were identified as hub genes in the PPI network. Subsequently, a statistically increased expression level of TRIM31 and ELF3 was validated by real-time quantitative-polymerase chain reaction and immunohistochemistry in bladder tissues from 20 patients with IC/BPS. CONCLUSIONS: TRIM31 and ELF3 may be the two hub genes in urothelium corresponding to IC/BPS. More studies are warranted to further validate the findings. The identified marker genes may be useful targets for further studies to develop diagnostic tools and more effective therapies for a broader group of women with IC/PBS.

Is imidafenacin an alternative to current antimuscarinic drugs for patients with overactive bladder syndrome?

PURPOSE: Previous studies have included a limited number of randomized controlled trials (RCTs) and compared limited parameters after treatment with imidafenacin and other anticholinergic drugs (ADs) for overactive bladder syndrome (OAB), and controversy about the superiority of these ADs still remains. We aim to update the evidence and provide better clinical guidance. METHODS: A systematic search of PubMed, Embase, ClinicalTrial.gov and Cochrane Library Central Register of Controlled Trials was conducted from January 2007 to April 2019. Meta-analysis of all published RCTs comparing imidafenacin with other ADs in patients with OAB was performed. The primary outcomes were the changes in OAB symptoms and OAB symptom score (OABSS). Secondary outcomes included adverse events (AEs) and the dropout rate related to AEs. RESULTS: A total of 6 studies including 7 RCTs involving 1430 patients with mean follow-up of 23.43 weeks were included. All ADs improved OAB symptoms. Regarding efficacy, these drugs had similar efficacy in voids, urgency episodes, urgency incontinence episodes, incontinence episodes and OABSS. However, imidafenacin performed better in the reduction of nocturia episodes (MD = -0.24, 95% CI -0.44 to -0.04, P = 0.02). Moreover, imidafenacin was associated with a statistically lower dry mouth rate (RR = 0.87, 95% CI 0.75-1.00, P = 0.04), lower constipation rate (RR = 0.68, 95% CI 0.50-0.93, P = 0.01) and lower AE-related withdrawal rate (RR = 0.51, 95% CI 0.29-0.89, P = 0.02). There was no significant difference in terms of other complications. CONCLUSIONS: In conclusion, imidafenacin was comparable to other ADs in the treatment of OAB. Moreover, imidafenacin presented a lower dry mouth rate, lower constipation rate and higher adherence and persistence.

Efficacy and safety comparison of pharmacotherapies for interstitial cystitis and bladder pain syndrome: a systematic review and Bayesian network meta-analysis.

INTRODUCTION AND HYPOTHESIS: The objective was to compare the clinical efficacy and safety of pharmacological interventions for interstitial cystitis and bladder pain syndrome (IC/BPS) with direct and indirect evidence from randomized trials. METHODS: We searched PubMed, the Cochrane library, and EMBASE for randomized controlled trials (RCTs) that assessed the pharmacological therapies for IC/BPS. Primary efficacy outcomes included ICSI (O'Leary Sant Interstitial Cystitis Symptom Index), ICPI (O'Leary Sant Interstitial Cystitis Problem Index), 24-h micturition frequency, visual analog scale (VAS), and Likert score for pain. Safety outcomes are total adverse events (AEs, intravesical instillation, and others), gastrointestinal symptoms, headache, pain, and urinary symptoms. A systematic review and Bayesian network meta-analysis were performed. RESULTS: A total of 23 RCTs with 1,871 participants were identified. The ICSI was significantly reduced in the amitriptyline group (MD = -4.9, 95% CI: -9.0 to -0.76), the cyclosporine A group (MD = -7.9, 95% CI: -13.0 to -3.0) and the certolizumab pegol group (MD = -3.6, 95% CI:-6.5 to -0.63) compared with placebo group. Moreover, for ICPI, cyclosporine A showed superior benefit compared to placebo (MD = -7.6, 95% CI: -13 to -2.3). VAS score improved significantly in cyclosporine A group than pentosan polysulfate sodium (MD = 3.09, 95% CI: 0.13 to 6.07). None of the agents revealed a significant alleviation of 24-h micturition frequency. In terms of safety outcomes, the incidence rate on urinary symptoms for botulinum toxin A was the only variate higher than chondroitin sulfate (MD = -2.02, 95% CI: -4.99 to 0.66) and placebo (MD = -1.60, 95% CI:-3.83 to 0.17). No significant difference was found among the other treatments. CONCLUSIONS: Cyclosporine A might be superior to other pharmacological treatments in efficacy. Amitriptyline and certolizumab pegol were capable of lowering the ICSI as well.

Metabolic syndrome in women with and without interstitial cystitis/bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the frequency of metabolic syndrome (MetS) in patients with and without interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: This case-control study evaluated the indicators of MetS in 287 females with IC/BPS and in 287 females without IC/BPS in West China Hospital between January 2010 and January 2020. Then, the number of voids per day, frequency of night urination, O'Leary-Sant Interstitial Cystitis Symptom/Problem Index, and visual analog scale were examined in the two groups. RESULTS: Based on both the National Cholesterol Education Program Adult Treatment Panel III recommendations and the International Diabetes Federation criteria, the distribution of MetS was statistically higher in patients with IC/BPS than in the control group, with 34.8% vs 17.8% (P < 0.0001) and 34.2% vs 20.9% (P = 0.0005), respectively. Regarding symptom scores, the IC/BPS group demonstrated significantly higher scores than the control group in all aspects (P < 0.0001). More patients with anxiety (P < 0.0001), insomnia (P < 0.0001), hypertension (P = 0.0001), and diabetes mellitus (P = 0.017) were observed in the IC/BPS group. Moreover, the findings indicated that patients with IC/BPS had a higher BMI (P = 0.0001) and larger waist circumference (P = 0.0001). Blood tests presented a significantly higher level of fasting glycemia, serum cystatin-C, and triglycerides in patients with IC/BPS. Furthermore, higher ORs for the occurrence of MetS among cases were observed, although this was not statistically significant. CONCLUSIONS: MetS frequency was relatively high in patients with IC/BPS. Further research is needed to understand the common pathophysiologic mechanism of IC/BPS and MetS.

Is absorbable suture superior to permanent suture for uterosacral ligament suspension?

AIMS: The aims of this study were to compare surgical results and suture-related complications after uterosacral ligament suspension (USLS) with absorbable suture (AS) vs permanent suture (PS). METHODS: We systematically searched PubMed, Embase, clinicalTrial.gov, and Cochrane Library Central Register of Controlled Trials for articles that compared AS with PS for USLS. The primary outcomes were surgical success rate and suture-related complications (suture exposure/erosion and suture removal). Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) was applied to conduct all analyses. RESULTS: Four articles involving 647 patients were eventually included. Our findings demonstrated that AS had a similar surgical success rates in comparison with PS (RR = 1.00; 95% CI, 0.94-1.06) and that no significant differences in anatomic failure rates were noted between two groups (RR = 1.10; 95% CI, 0.65-1.86). Subgroup analyses in anatomic failure revealed no statistical differences in apical prolapse ≥1/2 TVL (RR = 0.92; 95% CI, 0.48-1.75), recurrent prolapse beyond the hymen (RR = 1.18; 95% CI, 0.68-2.04), as well as in recurrent anterior, posterior or apical prolapse (P = .14, P = .08, P = .09, respectively). However, AS group indicated a lower risk in suture exposure/erosion (RR = 0.31; 95% CI, 0.15-0.63) and lower suture removal rate (RR = 0.35; 95% CI, 0.18-0.67). CONCLUSIONS: Due to similar surgical results, less suture exposure/erosion and less suture removal, the current data supported that AS is as effective as PS, but with a better safety profile.

Holmium laser technologies versus photoselective greenlight vaporization for patients with benign prostatichyperplasia: a meta-analysis.

This study aims to compare the efficacy and safety of holmium laser technologies (HoL-Ts) and photoselective greenlight vaporization (PVP) for the treatment of benign prostatic hyperplasia (BPH), and to perform a meta-analysis according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines on PubMed, EMBASE, ClinicalTrial.gov, and the Cochrane Central Register of Controlled Trials up to August 2019. Functional outcomes, perioperative parameters, and complications were included and analyzed. Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) was used to perform all analyses. A total of six articles composed of 2014 patients were included in this review. In comparison with PVP, HoL-Ts had a better performance in 1-, 3-, and 6-month Qmax (P = 0.02, but I2 = 81%), with less postvoid residual urine volume (PVR) (MD = -33.85, 95% CI -52.13 to -15.57, P = 0.0003) and less total energy used (MD = -31.66, 95% CI -58.99 to -4.33, P = 0.02). Moreover, HoL-Ts had a relatively lower risk of conversion rate (OR = 0.08, 95% CI 0.01 to 0.60, P = 0.01) associated with enough enucleation and less intraoperative bleeding. Subgroup analysis of holmium laser enucleation of prostate (HoLEP) versus PVP suggested that HoLEP presented better results in 1-, 3-, 6-month and 1-year Qmax with less PVR, less energy consumption, and lower conversion rate. Compared with PVP, HoL-Ts had higher 1-, 3-, and 6-month Qmax, less PVR, and less total energy consumption with a relatively lower risk of conversion rate. In subgroup analyses, HoLEP had shown better results in accordance with all HoL-Ts. Nevertheless, well-designed RCTs including overall functional indicators are required to confirm our findings.

Results of Sacral Neuromodulation Therapy for Urinary Voiding Dysfunction: Five-Year Experience of a Retrospective, Multicenter Study in China.

PURPOSE: This five-year, retrospective, multicenter study evaluated the long-term safety and efficiency of sacral neuromodulation (SNM) in Chinese patients with urinary voiding dysfunction. PATIENTS AND METHODS: This is a Chinese national, multicenter, retrospective study that included 247 patients (51.2% female) who received an implantable pulse generator (IPG) (InterStim, Medtronic, Minneapolis, MN, USA) between 2012 and 2016. Success was considered if the initial ≥50% improvement in any of primary voiding diary variables persisted compared with baseline. The results were further stratified by identifying patients who showed >50% improvement and those although showed <50% improvement but still wanted to receive IPG; these data were collected and analyzed for general improvement. RESULTS: Following test stimulation, 187 patients (43%) declined implantation and 247 (57%) underwent implantation using InterStim®. Among 247 patients, 34 (13.7%) had overactive bladder (OAB), 59 (23.8%) had interstitial cystitis/bladder pain syndrome (IC/BPS), 47 (19%) had idiopathic urinary retention (IUR), and 107 (44.1%) had neurogenic bladder (NB). IPG efficiency rate for OAB, interstitial cystitis/bladder pain syndrome, idiopathic urinary retention, and neurogenic bladder were 42.5, 72.4, 51.6, and 58.8%, respectively. The mean duration of follow-up was 20.1 ± 12.8 months. CONCLUSIONS: SNM appears effective in the long term, with a total IPG implantation rate of approximately 57% (ranging between 42.5 and 72.4% depending on indication). Interstitial cystitis/bladder pain syndrome appear to be the best indication for stage I testing. Chinese neurogenic bladder patients are most inclined to choose SNM. SNM is relatively safe, with low postoperation adverse events of 16.1% and reoperation rate of 3.2% during the follow-up period.

Risk factors of postoperative sexual function in patients with urethral diverticulum and their partners: A cohort study of 83 women.

INTRODUCTION AND OBJECTIVE: Several studies have focused on the treatment and recurrence of urethral diverticulum (UD). However, few investigations have addressed sexual function in pati-ents with UD. Therefore, we sought to examine sexual function in women affected by UD. MATERIALS AND METHODS: There were 108 accepted cases involving transvaginal diverticulectomy at our institution. Ultimately, 83 women were included for further analysis, only 61 of these wo-men had sexual partners. We collected data for the Female Sexual Function Index (FSFI) from the female patients and the Male Sexual Health Questionnaire (MSHQ) from their male partners before and after surgery. RESULTS: Preoperatively, the UD size affected the female patient's arousal and lubrication (p=0.04), and the UD location affected their satisfaction. However, no significant between-group differences were found in the total FSFI score. For all women, sexual activity improved after surgery (p=0.0087). In addition to improvements in arousal for women with a large UD, improvements in lubrication were affected by the UD size, number and shape, increases in sa-tisfaction scores were impacted by the UD location and shape, and pain relief was linked to the UD number and shape. Analysis of the MSHQ results revealed no between-group differences among the male partners. CONCLUSION: Only the UD size and location affected sexual function in women with a small UD. Surgery could improve female sexual function but did not affect the sexual function of the patient's partners.

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.

Identification of key genes and construction of microRNA-mRNA regulatory networks in bladder smooth muscle cell response to mechanical stimuli using microarray expression profiles and bioinformatics analysis.

PURPOSE: To identify keys genes and elucidate miRNA-mRNA regulatory networks in Bladder smooth muscle cell (BSMC) response to mechanical stimuli. METHODS: Human BSMCs, seeded on a silicone membrane, were subjected to mechanical stretch or without stretch. Microarray was used to analyze the differential expression of mRNAs and miRNAs between human BSMCs under mechanical stretch and control static control group. Differentially expressed genes(DEGs) and miRNAs (DEMs) in these two groups were identified. Subsequently, differentially expressed DEGs were conducted with functional analysis, and then PPI network was constructed. Finally, miRNA-mRNA regulatory network was visualized using Cytoscape. RESULTS: 1639 significant DEGs and three DEMs were identified between the stretch group and control static group. The PPI network of DEGs was constructed by STRING, which was composed of 1459 nodes and 1481 edges, including 188 upregulated genes and 255 downregulated genes. Moreover, 36 genes in the PPI network were identified as hub genes in BSMCs response to mechanical stretch, e.g. CCNH, CPSF2, TSNAX, ARPC5 and PSMD3 genes. Subsequently, 39 clusters were selected from PPI network using MCODE, and it was shown that the most significant cluster consisted of 14 nodes and 91 edges. Besides, miR-503HG was the most significantly downregulated miRNA and was predicted to target five upregulated genes, including SMAD7, CCND3, WIPI2, NYNRIN and PVRL1. CONCLUSIONS: Our data mining and integration help reveal the mechanotransduction mechanism of BSMCs' response to mechanical stimulation and contribute to the early diagnosis of bladder outlet obstruction (BOO) as well as the improvement of pathogenesis of BOO treatment.

Risk factors for recurrence in female urethral diverticulectomy: a retrospective study of 66 patients.

PURPOSE: We aimed to report surgical outcomes in female urethral diverticula and to investigate the risk factors for diverticula recurrence. METHODS: A total of 66 patients underwent urethral diverticulectomies from January 2009 to October 2015 at out institution. Patient and diverticula characteristics were collected. Mean follow-up was 28.8 months (range 4-85 months). Recurrence was defined as requiring a repeat diverticulectomy. RESULTS: Mean age was 44.9 years. Mean duration of symptoms was 28.1 months. Seven cases had previous urethral surgeries. Mean diverticula size was 2.8 cm. Main clinical symptoms included dribbling (n = 41), vaginal mass (n = 41), dysuria (n = 33), frequency/urgency (n = 29), infection (n = 24), stress urinary incontinence (SUI) (n = 20) and dyspareunia (n = 8). 10 cases had proximal diverticula, 10 cases had multiple diverticula, and 35 cases had horseshoe/circumferential diverticula. Postoperatively, the recurrence rate was 19.7 %. Preoperative SUI disappeared in 14 cases, and de novo SUI was developed in six cases. One case developed urethral stricture, and no cases reported urinary fistula. Among 60 cases with pathological results, neoplastic change was seen in one case (1.7 %). Besides, atypical hyperplasia (n = 2) and metaplasia (n = 3) were observed. Univariate analysis suggested that age, duration, follow-up, diverticula size and diverticula shape were not associated with surgical outcomes. Patients with multiple diverticula (p = 0.032), proximal diverticula (p = 0.042) and those with previous urethral procedures (p = 0.004) were at risk of recurrent diverticula confirmed by multivariate logistic regression analysis. CONCLUSIONS: The surgical outcomes of urethral diverticulectomies were acceptable. Multiple diverticula, proximal diverticula and previous urethral surgery were three independent risk factors for recurrent diverticula.

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.