No abstract

Various microRNAs (miRNAs) have previously been demonstrated to exhibit an association with the process of bladder remodeling, induced by bladder outlet obstruction (BOO). However, little is known about miRNA and gene expression profiles and the molecular mechanism underlying bladder pathophysiological alterations. The present study used bioinformatic analysis technology to examine the altered miRNA and mRNA expression profiles of bladder tissue in a rat model of BOO and validate the involved signaling pathways. The gene expression profile data was downloaded from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were screened. Potential target genes of DEMs were predicted. The target genes and DEGs were used for further gene ontology (GO) analysis followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Database for Annotation, Visualization and Integrated Discovery. The present study additionally constructed a DEM‑DEG interaction network. A total of 9 DEMs (3 upregulated and 6 downregulated) were identified; 664 DEGs were screened. KEGG analysis revealed that the DEGs were involved in the regulation of the actin cytoske-leton, extracellular matrix (ECM) remodeling, cell adhesion and the cell cycle. Additionally, KEGG classification indicated that these genes were important in angiogenesis, and in the p53 and transforming growth factor‑β signaling pathways. Notably, rno‑miRNA (miR)‑26b and rno‑miR‑101b were the two larger nodes of the 7 obstruction‑associated DEMs and interacted with 32 and 27 DEGs, respectively. On removal of obstruction, few DEMs were present; however, 370 genes exhibited the opposite expression trend. The majority of pathways enriched for the DEGs were identified and were associated with ECM‑receptor interaction and focal adhesion. In the DEM‑DEG regulatory network, miR‑495, miR‑494 and their target genes were significantly differentially expressed. The present study demonstrated that miRNAs and genes may be potential biomarkers of bladder remodeling induced by BOO, and additionally provided novel insights into the molecular mechanisms underlying this disorder.

To investigate the effects of pirfenidone (PFD) on the attenuation of bladder remodeling, and the associated functional changes caused by partial bladder outlet obstruction (pBOO), the present study performed surgery on adult male Sprague‑Dawley rats produce a model of pBOO. The rats in the pBOO group were administered a placebo and, in the CMC group, PFD mixed with the placebo was administered orally at 500 mg/kg body weight each day for 5 weeks, from 1 week after surgery. The rat bladders were harvested for biochemical analysis following cystometry at the end of the 6 week period. The histopathology was determined using Masson's trichrome staining. The mRNA and protein levels of pro‑fibrotic growth factors and extracellular matrix subtypes were assessed. pBOO debilitated bladder function and caused the parameters from cystometry to increase significantly compared with those in the control group (P<0.05), which were mitigated significantly following PFD treatment (P<0.05). In terms of the histology, the rats in the pBOO group exhibited significant increases in bladder weight, muscle hypertrophy and deposition of collagens, which were suppressed by PFD treatment (P<0.05). Based on the biochemical analysis, significant increases in the mRNA levels of collagen subtypes and growth factors, and protein levels of profibrotic growth factors and α‑smooth muscle actin in the bladders of rats in the pBOO group were reduced following PFD treatment. PFD prevented bladder remodeling and attenuated bladder fibrosis and, therefore, mitigated the deterioration of bladder function during the initial stage of pBOO.

Abbreviations & Acronyms AUC = area under the curve AUR = acute urinary retention BCI = bladder contractility index BOO = bladder outlet obstruction BOOI = bladder outlet obstruction index BWT = bladder wall thickness DO = detrusor overactivity DWT = detrusor wall thickness IPP = intravesical prostatic protrusion IPSS = International Prostate Symptom Score IPSS -s = storage score IPSS -v = voiding score LUTS/BPO = lower urinary tract symptoms suggestive of benign prostatic obstruction MODS = multiple organ dysfunction symptom m P ura = maximum pressure of urethra NPV = negative predictive value P det Q max = pressure of detrusor at maximum flow rate PPV = positive predictive value PSA = prostate-specific antigen PVR = post-voiding residue Q max = maximum flow rate QoL = quality of life RI = resistive index ROC = receiver operating characteristic R res = weight ratio of resection R s/v = ratio of IPSS -s and IPSS -v TPV = total prostate volume T res = time of resection TURP = transurethral prostatectomy TURS = TUR syndrome TZV = transitional zone volume UDS = urodynamics UEBW = ultrasonic estimation of bladder weight US = ultrasonography UTI = urinary tract infection UUI = urge urinary incontinence W res = tissue weight of resection Objectives: To establish and to evaluate discriminant models to predict the outcomes of transurethral prostatectomy. Methods: Clinical data of patients treated with transurethral prostatectomy between January and December 2013 were collected, including medical history, symptoms, biochemical tests, ultrasonography and urodynamics. Surgical efficacy was evaluated at 6-month follow up. Predictive models were constructed by logistic regression. Receiver operating characteristic curve and diagnostic tests were used to test the accuracy of models before the predictive value between models was compared. Results: A total of 182 patients were included, with 73.6% having an effective outcome. History of recurrent urinary tract infection (OR 1.33), score of storage phase (OR 2.58), maximum flow rate (OR 2.11) and detrusor overactivity (OR 3.13) were found to be risk factors. International Prostate Symptom Score (OR 0.13), transitional zone index (OR 0.58), resistive index of prostatic artery (OR 0.46), bladder wall thickness (OR 0.78), ultrasonic estimation of bladder weight (OR 0.28), bladder outlet obstruction index (OR 0.20) and bladder contractility index (OR 0.83) were found to be protective factors. The areas under the curve of models using factors from ultrasonography and urodynamics were 0.792 and 0.829 respectively, with no significant difference being found between them (P = 0.348). Conclusions: Surgical efficacy of transurethral prostatectomy is positively correlated to severe voiding phase symptoms, outlet obstruction and better detrusor contractility, and negative correlated with urinary infection, severe storage phase symptoms and excessive detrusor contractibility. Ultrasonography might replace urodynamics in selecting patients for whom transurethral prostatectomy is more likely t...