Shared genetic effect of kidney function on bipolar and major depressive disorders: a large-scale genome-wide cross-trait analysis.

BACKGROUND: Epidemiological studies have revealed a significant association between impaired kidney function and certain mental disorders, particularly bipolar disorder (BIP) and major depressive disorder (MDD). However, the evidence regarding shared genetics and causality is limited due to residual confounding and reverse causation. METHODS: In this study, we conducted a large-scale genome-wide cross-trait association study to investigate the genetic overlap between 5 kidney function biomarkers (eGFRcrea, eGFRcys, blood urea nitrogen (BUN), serum urate, and UACR) and 2 mental disorders (MDD, BIP). Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Psychiatric Genomics Consortium. RESULTS: Using LD score regression, we found moderate but significant genetic correlations between kidney function biomarker traits on BIP and MDD. Cross-trait meta-analysis identified 1 to 19 independent significant loci that were found shared among 10 pairs of 5 kidney function biomarkers traits and 2 mental disorders. Among them, 3 novel genes: SUFU, IBSP, and PTPRJ, were also identified in transcriptome-wide association study analysis (TWAS), most of which were observed in the nervous and digestive systems (FDR < 0.05). Pathway analysis showed the immune system could play a role between kidney function biomarkers and mental disorders. Bidirectional mendelian randomization analysis suggested a potential causal relationship of kidney function biomarkers on BIP and MDD. CONCLUSIONS: In conclusion, the study demonstrated that both BIP and MDD shared genetic architecture with kidney function biomarkers, providing new insights into their genetic architectures and suggesting that larger GWASs are warranted.

Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate.

OBJECTIVES: To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC-P). PATIENTS AND METHODS: We performed targeted sequencing of plasma cell-free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC-P and 84 without IDC-P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients' survival outcomes was also explored. RESULTS: We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC-P harboured genomic alterations in DNA repair pathways, respectively (P = 0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC-P carriers compared to IDC-P non-carriers (11.8% [19/161] vs 2.4% [two of 84], P = 0.024). Germline BReast CAncer type 2 susceptibility protein (BRCA2) and somatic cyclin-dependent kinase 12 (CDK12) defects were specifically identified in IDC-P carriers relative to PAC (BRCA2: 8.7% [14/161] vs 0% and CDK12: 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC-P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 (NCOR2) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P = 0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC-P proportion of ≥10% vs those with an IDC-P proportion of <10% (6.4% [five of 78] vs 18.1% [15/83], P = 0.045). For IDC-P carriers, tumour protein p53 (TP53) mutation was associated with shorter castration-resistant-free survival (median 10.9 vs 28.9 months, P = 0.026), and BRCA2 alteration was related to rapid prostate-specific antigen progression for those receiving abiraterone treatment (median 9.1 vs 11.9 months, P = 0.036). CONCLUSION: Our findings provide genomic evidence explaining the aggressive phenotype of tumours with IDC-P, highlighting the potential therapeutic strategies for this patient population.

The role of interleukin-6/interleukin-6 receptor signaling in the mechanical stress-induced extracellular matrix remodeling of bladder smooth muscle.

Extracellular matrix (ECM) remodeling is strongly associated with pathological changes induced by bladder outlet obstruction (BOO). In this study, we investigated the role of interleukin-6 (IL-6) in mechanical stretch-induced ECM remodeling of bladder smooth muscle. To construct a BOO animal model, the urethras of female Sprague-Dawley rats were partially ligated. In addition, increased hydrostatic pressure and mechanical stretching were applied to human bladder smooth muscle cells (HBSMCs) as an in vitro model. The expression of rat inflammatory genes was analyzed using DNA microarrays. We used quantitative RT-PCR (qRT-PCR) and immunohistochemical staining to detect IL-6 in the bladder smooth muscle of rats. To determine the specificity of IL-6, small interfering ribonucleic acid (siRNA) transfection and IL-6 receptor inhibitor (SC144) were applied to HBSMCs. qRT-PCR with siRNA transfection was also used to determine the specificity of downstream signaling. Moreover, western blotting was conducted to verify the expression results. In the animal model, the expression of ECM components and inflammatory genes was significantly upregulated. The expression of IL-6 was increased at both the mRNA level and the protein level in BOO rats. In vitro, hydrostatic pressure, and mechanical stretching both promoted MMP7 and MMP11 expression. Additionally, downregulation of collagen III occurred in both the hydrostatic pressure group and the mechanical stretch group. However, the expression of fibronectin exhibited opposing patterns between the hydrostatic pressure and mechanical stretch groups. The application of targeted siRNA transfection and an inhibitor (SC144) that targeted IL-6 significantly reversed the changes in MMP7 and MMP11 under mechanical stress and partially increased the expression of collagen III and fibronectin. In summary, IL-6 participated in the ECM remodeling of HBSMCs under mechanical stress, indicating that IL-6 may play an essential role in BOO..

Catheters for intermittent catheterization: a systematic review and network meta-analysis.

STUDY DESIGN: Systematic review and network meta-analysis. OBJECTIVES: Intermittent catheterization (IC) is considered the standard treatment for neuro-urological patients who are unable to empty their bladders. The present study aimed to conduct a systematic evaluation and network meta-analysis of all available types of intermittent catheters, and determine which one is best suited for clinical use. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify relevant studies. Only randomized clinical trials (RCTs) were included. Five types of catheters were identified based on the included studies. A Bayesian network meta-analysis was then performed. The surface under the cumulative ranking (SUCRA) curve was used to determine the best catheter for each outcome. RESULTS: A total of 25 RCTs, involving 1233 participants, were included. The pooled odds ratios of symptomatic UTI were lower for two ready-to-use single-use catheters (gel-lubricated non-coated catheter, OR: 0.30, 95% CI 0.095-0.86; pre-activated hydrophilic-coated catheter, OR: 0.41, 95% CI 0.19-0.83) as compared to single-use non-coated catheter. In terms of patient satisfaction, the SUCRA results showed that the pre-activated hydrophilic-coated catheter may the preferred option (SUCRA = 82.8%). However, there were no significant differences in all outcome measures between traditional single-use non-coated catheters and clean non-coated catheters. CONCLUSION: Ready-to-use single-use catheters are associated with lower rates of UTI compared to traditional catheters. Patients may be most satisfied with the pre-activated one. For traditional single-use non-coated catheters and clean non-coated catheters, there is still no convincing evidence as to which is better. Thus, more well-designed trials are needed.

Participation in Virtual Urology Conferences During the COVID-19 Pandemic: Cross-sectional Survey Study.

BACKGROUND: Due to the influence of the COVID-19 pandemic, conventional face-to-face academic conferences have been restricted, and many of these conferences have moved onto the internet. OBJECTIVE: The aim of this study was to investigate the virtual conferences in the field of urology during the COVID-19 pandemic and provide suggestions for better organization of such conferences. METHODS: A cross-sectional survey was conducted from May 30 to June 15, 2020, in China. Our team designed a 23-item questionnaire to investigate the conferences attended by urologists during the COVID-19 pandemic. SPSS 22.0 (IBM Corporation) was applied to analyze the data collected. RESULTS: A total of 330 Chinese urologists participated in our survey, and the response rate was 89.7% (330/368). Among the participants, 40.9% (135/330) were associate chief physicians. The proportion of participants who took part in conventional face-to-face academic conferences decreased from 92.7% (306/330) before the COVID-19 pandemic to 22.1% (73/330) during the pandemic (P<.001). In contrast, the proportion of urologists who took part in virtual conferences increased from 69.4% (229/330) to 90% (297/330) (P<.001). Most urologists (70.7%, 210/297) chose to participate in the virtual conferences at home and thought that a meeting length of 1-2 hours was most appropriate. Among the urologists, 73.7% (219/297) reported that their participation in the virtual conferences went smoothly, while the remaining respondents reported that they had experienced lags in video and audio streaming during the virtual conferences. When comparing conventional face-to-face conferences with virtual conferences, 70.7% (210/297) of the respondents thought that both conference formats were acceptable, while 17.9% (53/297) preferred virtual conferences and 11.5% (34/297) preferred conventional face-to-face meetings. CONCLUSIONS: Virtual conferences are increasing in popularity during the COVID-19 pandemic; however, many aspects of these conferences could be improved for better organization.

M3 receptor modulates extracellular matrix synthesis via ERK1/2 signaling pathway in human bladder smooth muscle cells.

Extracellular matrix (ECM) accumulation plays a key role in the progression of bladder outlet obstruction (BOO). Muscarinic receptors have been widely reported to serve as pivotal regulators in lung tissue remodeling. However, the influence of them on human bladder smooth muscle cells (HBSMCs) and the underlying molecular mechanisms have not yet been evaluated. The purposes of the present study are to investigate the effect of muscarinic receptors on the synthesis of ECM in HBSMCs and the involvement of intracellular signal transducers. The results indicated that M1 -M5 muscarinic receptors were all encoded in HBSMCs. The expression rank order was M2 > M1 > M5 > M3 > M4 . The gene and protein expression of collagen I (COL1), TIMP-1, and TIMP-2 was carbachol (CCH) concentration-dependently enhanced. The synthesis of COL1 in the supernatant of cell culture medium was significantly elevated by exposure to CCH. The CCH-induced protein expression of COL1, TIMP-1, and TIMP-2, however, was obviously reduced by the pretreatment of muscarinic receptor antagonists, atropine, and M3 -preferring antagonist (1,1-dimethyl-4-diphenyl-acetoxypiperidinium iodide [4-DAMP]). Furthermore, ERK1/2 was activated by 100 µM CCH when compared with the control group and the pretreatment of ERK1/2 inhibitor significantly suppressed the synthesis of COL1 induced by 100 µM CCH. Besides, CCH-induced phosphorylation of ERK1/2 was remarkably restrained by the pretreatment of 4-DAMP. All in all, these findings demonstrated that M3 receptor can modulate extracellular matrix synthesis via the ERK1/2 signaling pathway, which may provide potential novel therapeutic targets for BOO.

ß-Adrenoceptor signaling regulates proliferation and contraction of human bladder smooth muscle cells under pathological hydrostatic pressure.

BACKGROUND: Partial bladder outlet obstruction (PBOO) promotes bladder detrusor hyperplasia, increases bladder pressure, and decreases bladder compliance. To extensively explore its underlying mechanism, our study aimed to investigate the effect of pathological hydrostatic pressure on human bladder smooth muscle cell (hBSMC) proliferation and contraction through ß-adrenoceptor (ADRB) signaling in vitro. METHODS: hBSMCs were subjected to pathological hydrostatic pressure (100 cm H2 O) to investigate the effect of ADRBs on the proliferation and contraction of hBSMCs treated with its agonists and/or antagonists. RESULTS: Firstly, exposure to 100 cm H2 O hydrostatic pressure significantly upregulated the expression of α-smooth muscle actin (α-SMA) in hBSMCs at 6 hours, and promoted cell proliferation at 24 hours. When subjected to hydrostatic pressure alone, hBSMCs treated with ADRB2 and ADRB3 agonists for 6 hours inhibited α-SMA expression compared with untreated cells. By contrast, hBSMCs treated with ADRB2 agonists for 24 hours suppressed cell proliferation compared with untreated cells. The two classical pathways of ADRB, protein kinase A (PKA), and exchange factor directly activated by cAMP (EPAC) inhibited the contraction of hBSMCs under hydrostatic pressure via regulating mothers against decapentaplegic homolog 2 (SMAD2) activity. The proliferation of hBSMCs was mainly regulated by the EPAC pathway through extracellular signal-regulated kinase 1/2 (ERK1/2) activity. CONCLUSION: The contraction of hBSMCs under hydrostatic pressure was regulated by ADRB2 and ADRB3 via the PKA/EPAC-SMAD2 pathway, and the proliferation of hBSMCs was regulated by ADRB2 via the EPAC-ERK1/2 pathway. Compared with ADRB3, ADRB2 played a predominant role under pathological hydrostatic pressure. These findings markedly uncovered the underlying mechanism of ADRBs in PBOO and provided new insights into the efficient treatment of patients with PBOO.

Does ductal adenocarcinoma of the prostate (DA) have any prognostic impact on patients with de novo metastatic prostate cancer?

BACKGROUND: The prognostic value of ductal adenocarcinoma of the prostate (DA) in nonmetastatic prostate cancer (PCa) has been identified in many studies. However, it remains unknown whether DA is an adverse prognostic factor in metastatic PCa (mPCa). METHOD: Data from 634 mPCa patients histopathologically documented with DA or/and acinar adenocarcinoma of the prostate in our center between 2012 and 2018 were retrospectively analyzed. Propensity score matching (PSM) was used to balance the baseline features. Data from the Surveillance, Epidemiology, and End Results (SEER) database were utilized to validate our findings. Castration-resistant PCa-free survival (CFS), overall survival (OS), and cancer-specific survival (CSS) were set as endpoints. RESULTS: DA was confirmed in 35 of 634 (5.5%) patients. Among the DA-positive patients, 7 of 35 (20%) and 28 of 35 (80%) harbored high (DA ≥ 50%) and low (DA < 50%) DA components, respectively. DA was not associated with poorer median CFS (mCFS) or median OS (mOS) either before PSM (mCFS: 16.9 vs 18.4 month, P = .814; mOS: 42.0 vs 70.1 month, P = .796) or after PSM (mCFS: 16.9 vs 16.9 month, P = .949; mOS: 42.0 vs 79.9 month, P = .960). Likewise, in the SEER data, DA-positive patients (n = 15 153) shared similar median CSS (25.0 vs 28.0 month, P = .206) and OS (26.0 vs 35.0 month, P = .095) with DA-negative patients (n = 70). No prognostic difference was found between patients with high and low DA components. CONCLUSION: We conducted the first study investigating the prognostic value of DA in de novo mPCa. DA was not associated with adverse clinical outcomes in mPCa patients. These findings are helpful for prognostic evaluation, treatment decision making and counseling in mPCa patients.

The Prognostic Value of the Proportion and Architectural Patterns of Intraductal Carcinoma of the Prostate in Patients with De Novo Metastatic Prostate Cancer.

PURPOSE: Intraductal carcinoma of the prostate is an adverse prognosticator of prostate cancer. However, the roles of proportion and architectural patterns of intraductal prostate carcinoma in patient outcomes remain unclear. MATERIALS AND METHODS: We retrospectively analyzed data on 644 patients with de novo metastatic prostate cancer between 2010 and 2017. Intraductal carcinoma of the prostate was identified from 12-core prostate biopsy. We calculated the proportion of intraductal prostate carcinoma and identified patterns according to the 2016 WHO classification. Propensity score matching was performed to balance baseline characteristics between patients with and without intraductal prostate carcinoma. Kaplan-Meier curves and Cox regression were used for survival analyses. The end points were castration resistant prostate cancer-free survival and overall survival. RESULTS: Of the 644 patients 180 (28.0%) harbored intraductal carcinoma of the prostate. A 10% or greater incidence of the carcinoma was independently associated with worse prognosis (castration resistant prostate cancer-free survival HR 2.06, 95% CI 1.51-2.81, p <0.001, and overall survival HR 2.52, 95% CI 1.52-4.16, p <0.001), as was pattern 2 intraductal carcinoma of the prostate (HR 1.86, 95% CI 1.40-2.49, p <0.001, and HR 2.12, 95% CI 1.29-3.46, p = 0.003, respectively). Based on these 2 risk factors all men were classified into 5 groups. Patients in group 0 (no intraductal carcinoma of the prostate) and prostate intraductal carcinoma group 1 (less than 10% intraductal carcinoma, pattern 1) had favorable median castration resistant prostate cancer-free survival (18.0 vs 16.9 months, p = 0.871) and median overall survival (neither reached, p = 0.698). Men in intraductal carcinoma of the prostate group 4 (10% or greater intraductal carcinoma, pattern 2) harbored the worst outcomes (median castration resistant prostate cancer-free and overall survival 8.4 and 29.9 months, respectively). Group 2 (less than 10% intraductal carcinoma, pattern 2, with median castration resistant prostate cancer-free and overall survival 14.2 and 45.9 months) and group 3 (10% or less prostate intraductal carcinoma, pattern 1, with median castration resistant prostate cancer-free and overall survival 11.9 and 39.7 months, respectively) had an intermediate prognosis. CONCLUSIONS: A 10% or greater proportion of intraductal carcinoma of the prostate and pattern 2 were 2 unfavorable prognosticators of metastatic prostate cancer. Pathological reporting criteria based on intraductal carcinoma of the prostate could improve the prediction of patient outcomes and optimize treatment decisions.

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

PURPOSE: To systematically evaluate the different efficacy among generally used drugs for stent-related symptoms (SRS) with the method of network meta-analysis. METHODS: A 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. RESULTS: 19 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%). CONCLUSIONS: Tam 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.

Hypertension as a prognostic factor in metastatic renal cell carcinoma treated with tyrosine kinase inhibitors: a systematic review and meta-analysis.

BACKGROUND: Conflicting evidence exists regarding the effect of hypertension on the prognosis of metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). This study aimed to assess the predictive value of TKIs-induced hypertension in patients with mRCC. METHODS: This study was registered in PROSPERO (CRD42019129593). PubMed, Embase, Web of Science and the Cochrane Library database were searched with terms: "renal cell carcinoma", "hypertension", "blood pressure", "tyrosine kinase inhibitor", "sunitinib", "axitinib", "sorafenib" and "pazopanib" until March 21, 2019. Hazard Ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) or overall survival (OS) were extracted and analyzed with Stata 15.0 software. Heterogeneity was assessed using the I2 value. Meta-regression, subgroup analysis and sensitivity analysis were also performed to explore heterogeneity. Publication bias was assessed with funnel plots and precisely assessed by Egger's and Begg's tests. The quality of evidence of outcomes was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: A total of 4661 patients from 22 studies were included in the study. The results showed that the increase of blood pressure was an effective predictor for longer PFS (HR = 0.59, 95% CI: 0.48-0.71, p < 0.001; I2 = 77.3%) and OS (HR = 0.57, 95% CI: 0.45-0.70, p < 0.001; I2 = 77.4%) of patients with mRCC. Subgroup analysis revealed that patients receiving sunitinib and pazopanib could have longer PFS and OS. CONCLUSIONS: This study indicated that TKIs-induced hypertension may be a good predictor for better prognosis of patients with mRCC receiving TKIs treatment, especially using sunitinib or pazopanib.

The application of barbed suture during the partial nephrectomy may modify perioperative results: a systematic review and meta-analysis.

BACKGROUND: Barbed sutures can avoid knot tying and speed the suture placement in the PN(partial nephrectomy). On account of the impact on clinical outcomes are ambiguous, this study is determined to identify the application of barbed suture during PN. METHODS: ClinicalTrials.gov, Cochrane Register of Clinical Studies, PubMed and EMBASE were searched for RCTs(randomized controlled trials) and cohort studies focusing on the comparison of barbed and traditional sutures in PN(last updated on Feb in 2015). According to Cochrane Library's suggestion, quality assessment was performed. Review Manager was applied to analyze all the data and sensitivity analyses were performed through omitting each study sequentially. RESULTS: Eight cohort studies and none of RCTs proved eligible (risk of bias: moderate to low,431 patients). Warm ischemia time(MD = - 6.55,95% CI -8.86 to - 4.24, P < 0.05) decreased statistically in the barbed suture group, as well as operative time(MD = - 11.29,95% CI -17.87 to-4.71, P < 0.05). Postoperative complications also reduced significantly(OR = 0.44, 95% CI 0.24 to0.80, P < 0.05). Unidirectional barbed suture resulted in fewer postoperative complications based on the subgroup analysis(OR = 0.48,95% CI 0.24 to 0.94, P < 0.05). CONCLUSIONS: The barbed suture may be a useful surgical innovation which can modify perioperative results for surgeons and patients. Randomly-designed studies with longer follow up and larger sample sizes are in the need of to explore the applicability.

Which is the best treatment of pediatric upper urinary tract stones among extracorporeal shockwave lithotripsy, percutaneous nephrolithotomy and retrograde intrarenal surgery: a systematic review.

BACKGROUND: Although the indications of minimally invasive treatments for pediatric urolithiasis are similar to those in adults, it is still crucial to make the right treatment decision due to the special considerations of children. This review aims to evaluate the efficacy and safety of extracorporeal shockwave lithotripsy (SWL), percutaneous nephrolithotomy (PCNL), and retrograde intrarenal surgery (RIRS) in the management of pediatric upper urinary tract stones. METHODS: EMBASE, PubMed, and the Cochrane Library were searched from their first available date to March 2018. The studies that meet the inclusive criteria were included. The efficacy and safety of the treatments were assessed by means of meta-analysis of the stone free rate (SFR), complication rate, effectiveness quotient (EQ) and secondary outcome indicators. RESULTS: A total of 13 comparative studies were identified for data analysis. PCNL presented a significantly higher SFR compared with SWL. Similarly, the single-session SFR of RIRS was significantly higher than SWL. However, no significant difference was found between RIRS and SWL in the overall SFR. There was no significant difference between PCNL and RIRS in the SFR. Furthermore, no significant differences in complication rates were found among the three therapies. Compared with the other two treatments, PCNL had a longer operative time, fluoroscopy time and hospital stay. SWL had a shorter hospital stay, higher retreatment rate and auxiliary rate in comparison with the other two treatments. The present data also showed that PCNL presented a higher EQ than the other two treatments, and RIRS had a lower efficiency than SWL and PCNL. In the subgroup analysis of pediatric patients with stone ≤20 mm, the comparative results were similar to those described above, except for the higher complication rate of PCNL than SWL. CONCLUSIONS: Although SWL as an outpatient procedure provides shorter hospital stay and reduces operative time, it has a lower SFR and higher retreatment rate than the other two treatments. PCNL exhibits a higher SFR and EQ than SWL; nevertheless, it has a longer operative time and fluoroscopy time than the other two procedures. RIRS offers a similar SFR as PCNL but a lower efficiency than PCNL.

Novel nomograms for castration-resistant prostate cancer and survival outcome in patients with de novo bone metastatic prostate cancer.

OBJECTIVES: To develop nomograms predicting the incidence of castration-resistant prostate cancer (CRPC) and overall survival (OS) for de novo metastatic prostate cancer (PCa). PATIENTS AND METHODS: Data from 449 patients with de novo metastatic PCa were retrospectively analysed. Patients were randomly divided into a training (n = 314, 70%) and a validation cohort (n = 135, 30%). Predictive factors were selected using a Cox proportional hazards model and were further used for building predictive models. The outcomes were incidence of CRPC and OS. RESULTS: Predictive factors included: Gleason score (GS), intraductal carcinoma of the prostate (IDC-P), Eastern Cooperative Oncology Group status, and alkaline phosphatase, haemoglobin and prostate-specific antigen levels. IDC-P and GS were the strongest prognosticators for both the incidence of CRPC and OS. Nomograms for predicting CRPC and OS had an internal validated concordance index of 0.762 and 0.723, respectively. Based on the ß coefficients of the final model, risk classification systems were constructed. For those with favourable, intermediate and poor prognosis, the median time to CRPC was 62.6, 28.0 and 13.0 months (P < 0.001), respectively; and the median OS was not reached, 55.0 and 33.0 months, respectively (P < 0.001). CONCLUSIONS: We developed two novel nomograms to predict the incidence of CRPC and OS for patients with de novo metastatic PCa. These tools may assist in physician decision-making and the designing of clinical trials.

Perineal midline vertical incision verses inverted-U incision in the urethroplasty: which is better?

OBJECTIVE: To compare postoperative outcomes between the perineal inverted-U and the vertical midline incision approaches of the urethroplasty and clarify them via gross anatomy. PATIENTS AND METHODS: A total of 461 male patients, from Jan. 2006 to Jun. 2014, who underwent the urethroplasty via perineal midline vertical or inverted-U incision approach were recruited retrospectively. By match pairing for etiology and stricture length, 410 patients from two groups (205 for each group) were selected. Anatomy experiments were also performed. Outcome measurements and statistical analysis: the Chi-square, Student's t and binary logistic regression analyses were performed to compare the operative and postoperative data on the two groups. RESULTS: With regard to patients with bulbar urethral stricture, the rate of surgical site infection (SSI) in perineal inverted-U group was 18.6% while 1.9% in the midline vertical group (p < 0.001). As for patients with posterior urethral stricture, the rate of SSI in the perineal inverted-U group was 16.4% while 3.1% in the midline vertical group (p = 0.001). Mean hospital stay between both groups were 15.8 ± 9.0 vs. 12.7 ± 3.8 days (p < 0.001). Anatomy experiments showed the number of damaged vessels and nerves involved in the inverted-U incision were approximately 1.6 to 2.0 folds more than the vertical midline, but the visual operation fields are similar between two approaches. CONCLUSIONS: The perineal midline vertical incision is a safer approach with fewer SSI and shorter hospital stay than the perineal inverted-U incision for bulbar and posterior urethroplasty.

Physiological stretch induced proliferation of human urothelial cells via integrin α6-FAK signaling pathway.

AIMS: To test a kind of stretch pattern which is the optimum stress parameter to promote human urothelial cells (HUCs) proliferation, and to investigate the roles of integrin subunits and their pathway in the HUCs proliferation induced by physiological stretch. METHODS: HUCs were seeded on silicone membrane, and subjected to four kinds of stretch (0,5%,10%,15% elongation) for 24 h, as controlled by a BioDynamic® bioreactor. Cell proliferation, viability and cycle distribution were examined using Cell Counting Kit-8 and flow cytometry, respectively. The gene and protein expression of integrin subunits and focal adhesion kinase (FAK) in each group were assessed by Real-time PCR(RT-PCR) and western blot, respectively. Small interfering RNAs (siRNA) were applied to knockdown integrin α6 and FAK expression in HUCs, and FAK inhibitor was used to validate the role of α6 and FAK in cell proliferation under physiological stretch. RESULTS: The proliferation of HUCs were highest in the 5% elongation group compared to static control, 10% and 15% elongation group. RT-PCR and western blot showed that 5% cyclic stretch significantly promoted the expression of integrin α6 and FAK. The stretch-induced cell proliferation and FAK expression was inhibited by siRNA of integrin α6. Further study with FAK inhibitor revealed that elongation promoted proliferation though integrin α6 and FAK signaling pathway. CONCLUSIONS: Physiological stretch induced HUCs proliferation via integrin α6-FAK signaling pathway, and 5% elongation may be the optimal stress parameter to promote the cell proliferation.

Paraneoplastic Cerebellar Degeneration Associated with Pelvic Liposarcoma: A Rare Case Report.

Paraneoplastic cerebellar degeneration (PCD) is one of the most common paraneoplastic neurological syndromes characterized by the rapid development of severe cerebellar ataxia. In this report, a 23-year-old female with noticeable dizziness and gait instability was described. The enhanced CT scanning suggested the presence of a pelvic tumor. Then, PCD was established. Postoperative pathological result defined it as a liposarcoma (LS) with dedifferentiation. Interestingly, clinical symptoms disappeared after the surgical removal of the pelvic tumor. To our knowledge, this was the first case report with PCD due to LS.

[Risk Factors for Wound Healing of Infective Surgical Incision after Radical Cystectomy in Patients of Muscle Invasive Bladder Cancer].

OBJECTIVE: To evaluate the risk factors for wound healing of infective surgical incision in patients of muscle invasive bladder cancer undergoing radical cystectomy. METHODS: This study retrospectively collected clinical data of the patients who received radical cystectomy and experienced incisional infection after operation between January 2009 and December 2016. The patients were divided into early healing group and delayed healing group (the healing time is less or more than 14 d after operation). The risk factors for wound healing and infection were analyzed by single factor and multivariate logistic regression. RESULTS: A total of 171 patients with wound infection after radical cystectomy were included in the study. The average time of wound healing time was (17.9±16.9) d. There were 118 and 53 patients in early healing group and delay healing group respectively. Age, body mass index (BMI), operative incision type, preoperative albumin level, diabetes mellitus, infection wound size, infection wound with sinus, postoperative intestinal fistula and urinary fistula were statistically significant differences between the two groups (P<0.05).Univariate logistic regression analysis indicated that male, older than 65 yr., T4 stage, Type-Ⅲ surgical incision (infective incision), low preoperative albumin level (<30 g/L), hemoglobin level (<90 g/L), diabetes, wound size (>30 mm), intestinal fistula, urinary fistula were risk factors for delayed wound-healing. Multivariate logistic regression analysis revealed that Type-Ⅲ surgical incision and wound size (>30 mm) were independent risk factors for delayed wound healing. CONCLUSION: Type-Ⅲ surgical incision and the size of wound (>30 mm) are independent risk factors for delayed wound healing after radical cystectomy in bladder cancer patients.

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.

Does body mass index influence the outcome of midurethral sling procedures for stress urinary incontinence?

INTRODUCTION AND HYPOTHESIS: Whether midurethral sling (MUS) procedures are as effective in obese women as they are in women of normal weight is still a matter of controversy. The objective of this study was to determine if body mass index (BMI) influences the outcome of MUS procedures for stress urinary incontinence (SUI). METHODS: We searched electronic databases including EMBASE, MEDLINE, Web of Science and Ovid evidence-based medicine reviews to identify studies that explored the association between BMI and outcomes of MUS procedures. The studies were rated using the Newcastle-Ottawa scale; the meta-analysis was performed using Review Manager 5.3 software. RESULTS: This review included 11 studies, 6 prospective cohort studies and 5 retrospective studies, with a total of 2,846 patients. The objective success rates of MUS in patients with BMI >25 kg/m2 (overweight and obese) were lower than in patients with BMI 18.5 - <25 kg/m2 (normal weight; RR = 0.93, 95 % CI 0.89 - 0.97; P = 0.002). The objective success rates were not significantly different between the overweight group (BMI 25 - <30 kg/m2) and the obese group (BMI ≥30 kg/m2; RR = 0.95, 95 % CI 0.89 - 1.01; P = 0.08). There were no significant differences in subjective outcomes among the different BMI groups: BMI ≥25 kg/m2 versus 18.5 - <25 kg/m2 (RR = 1.03, 95 % CI 0.97 - 1.10; P = 0.29), and BMI ≥30 kg/m2 versus 25 - <30 kg/m2 (RR = 0.98, 95 % CI 0.92 - 1.04; P = 0.55). CONCLUSIONS: The objective success rates of MUS were lower in overweight and obese patients; however, the subjective outcomes of MUS were not significantly different among normal weight, overweight and obese patients. The MUS procedure is as effective in obese women as in women of normal weight, and therefore surgeons should not consider BMI >25 kg/m2 as a risk factor when discussing the suitability of the MUS procedure in a patient with SUI.