[Biological function of bladder smooth muscle cells regulated by multi-modal biomimetic stress].

Previous studies have shown that growth arrest, dedifferentiation, and loss of original function occur in cells after multiple generations of culture, which are attributed to the lack of stress stimulation. To investigate the effects of multi-modal biomimetic stress (MMBS) on the biological function of human bladder smooth muscle cells (HBSMCs), a MMBS culture system was established to simulate the stress environment suffered by the bladder, and HBSMCs were loaded with different biomimetic stress for 24 h. Then, cell growth, proliferation and functional differentiation were detected. The results showed that MMBS promoted the growth and proliferation of HBSMCs, and 80 cm H 2O pressure with 4% stretch stress were the most effective in promoting the growth and proliferation of HBSMCs and the expression level of α-smooth muscle actin and smooth muscle protein 22-α. These results suggest that the MMBS culture system will be beneficial in regulating the growth and functional differentiation of HBSMCs in the construction of tissue engineered bladder.

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.

Cyclic hydrostatic pressure promotes uroplakin expression in human urothelial cells through activation of ERK1/2 signaling.

OBJECTIVES: To investigate the effect of cyclic hydrostatic pressure on the expression of uroplakins and the role of extracellular regulated protein kinases 1/2 (ERK1/2) in the hydrostatic pressure-induced uroplakin expression of human urothelial cells (UCs). METHODS: Human UCs were seeded into a cell culture flask and subjected to cyclic hydrodynamic pressures for 24 h. Pressure parameters were set as follows: static, 100 cm H2O, 200 cm H2O and 300 cm H2O pressure. Real-time polymerase chain reaction (RT-PCR) and western blot were used to detect the expression of uroplakins. The role of the ERK1/2 was investigated using ERK1/2 inhibitor. RESULTS: Compared with the 0 cm H2O control group, 200 cm H2O hydrostatic pressure significantly increased the expression of uroplakins, however, 100 cm and 300 cm pressures could not promote uroplakin expression. Hence, ERK1/2 expression was also detected under 200 cm H2O hydrostatic pressure. Western blot showed that 200 cm H2O pressure promoted the expression of ERK1/2. ERK1/2 inhibitor decreased the pressure-induced ERK1/2 activivation and uroplakin expression. CONCLUSIONS: Cyclic hydrostatic pressure increases the expression of uroplakins via activating ERK1/2 signaling pathway in human UCs, and 200 cm H2O pressure may be an optimal stress parameter to promote the uroplakin expression.

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.

Comparison of Holmium: YAG Laser and Pneumatic Lithotripsy in the Treatment of Ureteral Stones: An Update Meta-Analysis.

PURPOSE: Holmium YAG laser lithotripsy (LL) and pneumatic lithotripsy (PL) are the most commonly used procedures in the treatment of ureteral calculi. In a previous meta-analysis examining the treatment effect of the 2 modalities, the authors highlighted the need for large sample size and high quality trials to provide more uncovered outcome. Recently, several randomized controlled trials (RCTs) evaluating the same issue with larger patient number and more complicated data have been published. Therefore, we conducted this meta-analysis to update and synthesize evidence on the efficacy and safety of the 2 procedures in the treatment of ureteral calculi. METHODS: The relevant studies were identified by searching Medline, EMBASE and Cochrane Library Database from January 1990 to November 2015. RCTs assessing the efficacy and safety of Holmium YAG laser and PL for ureteral stones were included. Two reviewers independently screened studies and extracted data. RESULTS: A total of 8 studies were identified including 1,555 patients. Compared with PL, Holmium YAG LL significantly reduced the mean operative time (weighted mean difference = -11.52, 95% CI -17.06 to -5.99, p < 0.0001) and increased the early stone-free rate (OR 2.69, 95% CI 1.91-3.78, p < 0.00001) and the delayed stone-free rate (OR 2.12, 95% CI 1.40-3.21, p = 0.0004). However, a higher postoperative ureteral stricture rate (OR 3.38, 95% CI 1.56-7.31, p = 0.002) was observed in LL group over PL group. There was no statistical significance in the ureteral perforation rate (OR 1.19, 95% CI 0.65-2.16, p = 0.58), the stone migration rate (OR 0.64, 95% CI 0.41-1.00, p = 0.05), the postoperative gross hematuria rate (OR 0.71, 95% CI 0.40-1.25, p = 0.23) and the postoperative fever rate (OR 0.73, 95% CI 0.50-1.09, p = 0.12). CONCLUSIONS: Our data reconfirmed that Holmium LL for ureteral stones can achieve shorter mean operative time, better early and delayed stone-free rate with larger sample size and more high quality studies. And further trials are unlikely to considerably alter this conclusion. In terms of higher risk of postoperative ureteral stricture in LL group over PL group observed in our review, more high quality, multicenter RCTs with long-term follow-up outcome are warranted to better assess this issue.

Magnitude-dependent proliferation and contractility modulation of human bladder smooth muscle cells under physiological stretch.

PURPOSE: The purpose of this study was to describe and test a kind of stretch pattern which is based on modified BOSE BioDynamic system to produce optimum physiological stretch during bladder cycle. Moreover, we aimed to emphasize the effects of physiological stretch's amplitude upon proliferation and contractility of human bladder smooth muscle cells (HBSMCs). METHODS: HBSMCs were seeded onto silicone membrane and subjected to stretch simulating bladder cycle at the range of stretches and time according to customized software on modified BOSE BioDynamic bioreactor. Morphological changes were assessed using immunofluorescence and confocal laser scanning microscope. Cell proliferation and cell viability were determined by BrdU incorporation assay and Cell Counting Kit-8, respectively. Contractility of the cells was determined using collagen gel contraction assay. RT-PCR was used to assess phenotypic and contractility markers. RESULTS: HBSMCs were found to show morphologically spindle-shaped and orientation at various elongations in the modified bioreactor. Stretch-induced proliferation and viability depended on the magnitude of stretch, and stretches also regulate contractility and contraction markers in a magnitude-dependent manner. CONCLUSION: We described and tested a kind of stretch pattern which delivers physiological stretch implemented during bladder cycle. The findings also showed that mechanical stretch can promote magnitude-dependent morphological, proliferative and contractile modulation of HBSMCs in vitro.

Integrin αv mediates contractility whereas integrin α4 regulates proliferation of human bladder smooth muscle cells via FAK pathway under physiological stretch.

PURPOSE: The requirement of integrins for mechanotransduction has been recognized for some time. We investigated the role of integrin subunits and their pathway in the physiological stretch induced contractility and proliferation of human bladder smooth muscle cells. MATERIALS AND METHODS: Human bladder smooth muscle cells were seeded on silicone membrane and subjected to stretch, simulating bladder cycles of various stretches and times, as controlled by customized software on a modified BioDynamic bioreactor. Cell proliferation, viability and cycle were determined by BrdU incorporation assay, the Cell Counting Kit-8 (Beyotime Institute of Biotechnology, Haimen, People's Republic of China) and flow cytometry, respectively. Cell contractility was determined using a collagen gel contraction assay. RESULTS: Physiological stretch increased cell contractility, proliferation and viability. Knockdown of integrin αv but not α4 in the cells disrupted the enhanced contractility induced by stretch. Under physiological stretch conditions, the integrin αv level and phospho-FAK/FAK ratio correlated positively with cell stretch induced enhanced contractility. Further examination revealed that contractile marker expression was associated with integrin αv activation through the FAK pathway. At the same time integrin α4 but not integrin αv mediated stretch induced cell proliferation and viability. CONCLUSIONS: These data revealed that different integrins have different roles in the contractility and proliferation of human bladder smooth muscle cells under physiological stretch. This suggests that different integrins may become specific therapeutic targets in patients with voiding dysfunction. They may also be used to design a specific microenvironment for optimal bladder tissue regeneration.

Simulated bladder pressure stimulates human bladder smooth muscle cell proliferation via the PI3K/SGK1 signaling pathway.

PURPOSE: A mechanical stimulus on detrusor tissue is critical to bladder outlet obstruction progression and functional bladder tissue engineering. A hypothesis is that mechanical stimulus triggers human bladder smooth muscle cell proliferation. To help better understand this relationship of bladder function to growth at the cellular level we used a novel method of applying cyclic hydrodynamic pressure that simulates the bladder cycle to cell cultures. We detected the proliferation response of human bladder smooth muscle cells (4310, ScienCell™) to different pressures as well as the signal transduction mechanism of this process. MATERIALS AND METHODS: Human bladder smooth muscle cells cultured in scaffolds underwent 4 pressures (0, 100, 200 and 300 cm H(2)O) for 24 hours, as controlled by a BioDynamic® bioreactor. We then used flow cytometry to examine cell cycle distribution, and polymerase chain reaction and immunoblot to quantify SGK1 and AKT expression and activation in each group. SGK1 was silenced in human bladder smooth muscle cells using small interfering RNA to validate the role of SGK1 in mediating pressure induced cell proliferation. RESULTS: Compared with the 0 cm H(2)O control group, human bladder smooth muscle cells in the 200 and 300 cm H(2)O groups showed increased cell proliferation. SGK1 expression and activity were also increased while AKT, another downstream signal of PI3K, did not change significantly. SGK1 silencing abolished the increases in cell proliferation induced by pressure. CONCLUSIONS: To our knowledge we provide the first report of cyclic hydrodynamic pressure stimulating the proliferation of human bladder smooth muscle cells cultured in scaffolds. The signal transduction mechanism for this process is involved with the PI3K/SGK1 and not the PI3K/AKT signaling pathway.

Effect of cyclic hydrodynamic pressure-induced proliferation of human bladder smooth muscle through Ras-related C3 botulinum toxin substrate 1, mitogen-activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2.

OBJECTIVES: To examine the role of Ras-related C3 botulinum toxin substrate 1, mitogen-activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2 in the cyclic hydrodynamic pressure-induced proliferation of human bladder smooth muscle cells. METHODS: Human bladder smooth muscle cells were exposed to cyclic hydrodynamic pressures in vitro with defined parameters (static, 100 cmH(2) O, 200 cmH(2) O and 300 cmH(2) O pressure) for 24 h. The proliferation of cells was assessed by flow cytometry. Ras-related C3 botulinum toxin substrate 1, mitogen-activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2 messenger ribonucleic acid, and protein expression was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the Rac1 was determined with real-time polymerase chain reaction and Western blot technique with small interfering ribonucleic acid transfection and Rac1 inhibitor (NSC23766). RESULTS: The proliferation of human bladder smooth muscle cells was increased. Ras-related C3 botulinum toxin substrate 1, mitogen-activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2 were activated by 200 and 300 cmH(2) O cyclic hydrodynamic pressure compared with static and 100 cmH(2) O pressure. The "knockdown" of activation of Rac1 using target small interfering ribonucleic acid transfection and Rac1 inhibitor (NSC23766) decreased proliferation of human bladder smooth muscle cells, and downregulated mitogen-activated protein kinase kinase 1/2, extracellular regulated protein kinases 1/2. CONCLUSION: The Rac1 pathway is activated in mechanotransduction and regulation of human bladder smooth muscle cell proliferation in response to cyclic hydrodynamic pressure.

[Effects of hydrostatic pressure in physiological range on bladder smooth muscle cells in vitro].

To explore the effects of the physiological range of hydrostatic pressure on human bladder smooth muscle cells (HBSMCs) cultured in vitro, we used a hydrostatic compression device designed in our laboratory into the experiments, which were grouped by varied hydrostatic pressure gradients. Cellular morphology was observed with HE staining; cytoskeleton F-actin, cell cycle, both proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 7 (MMP-7) were detected respectively with immunofluorescence, flow cytometry and RT-PCR. We found that the proliferation, cytoskeleton and cycle distribution of HBSMCs were not obviously different among the groups of different hydrostatic pressure; however, the mRNA expression of MMP-7 exhibited a trend of first increasing and then declining as the pressure gradually rises. Thus the physiological range of hydrostatic pressure may not have significant influence on proliferation, morphology, skeleton, and cell cycle of HBSMCs, but it may have great effect on the expression of MMP-7.

Application of intra-arterial chemotherapy in high-risk non-muscle invasive bladder cancer: a systematic review and meta-analysis.

BACKGROUND: To summarize the current evidence on the effects of intra-arterial chemotherapy (IAC) on high-risk non-muscle invasive bladder cancer (NMIBC) and compare oncology results with intravesical chemotherapy (IVC). METHODS: We performed a systematic review and cumulative meta-analysis of the primary outcomes of interest by a systematical search of multiple scientific databases in February 2021. The mean difference (MD) and odds ratio (OR) were calculated for continuous and dichotomous variables respectively, with 95% confidence intervals (CIs). The hazard radio (HR) with 95% CIs was used for overall survival (OS), recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: A total of six studies with 866 patients were included. For IAC combined with IVC versus IVC alone, statistically significant differences were found regarding tumor recurrence rate (OR: 0.51, 95% CI [0.36∼0.72], p = 0.0001), tumor progression rate (OR: 0.47, 95% CI [0.30∼0.72], p = 0.0006), tumor-specific death rate (OR: 0.49, 95% CI [0.25∼0.99], p = 0.05), PFS (HR: 0.47, 95% CI [0.23∼0.96], p = 0.04) and RFS (HR: 0.60, 95% CI [0.41∼0.87], p = 0.007). No significant difference between two groups was found for time to first recurrence (MD: 3.27, 95% CI [-2.37∼8.92], p = 0.26) and OS (HR: 1.20, 95% CI [0.44∼3.32], p = 0.72). For IAC alone versus IVC, There was no statistical difference in the terms of tumor-specific death rate (OR: 0.67, 95% CI [0.29∼1.53], p = 0.34), RFS (HR: 0.90, 95% CI [0.56∼1.46], p = 0.68) and PFS (HR: 0.71, 95% CI [0.32∼1.55], p = 0.39). Adverse events mainly included nausea/vomiting (36.3%), hypoleukemia (19.4%), neutropenia (16.0%), increased creatinine (9.9%), increased alanine aminotransferase (18.7%), and thrombocytopenia (9.9%). CONCLUSION: The IAC combined with IVC is a safe and effective treatment for high risk NMIBC, with lower rates of recurrence, progression, tumor-specific death, PFS and RFS, and with minor and tolerable events. The effectiveness of the IAC alone is parallel to the IVC alone.

Comparison of different laser-based enucleation techniques for benign prostate hyperplasia: A systematic review and meta-analysis.

BACKGROUND: To summarize the current evidence on different laser-based enucleation techniques for benign prostate hyperplasia and compare the efficacy and safety of en-bloc, two-lobe and three-lobe techniques. MATERIALS AND METHODS: Through a systematical search of multiple scientific databases in March 2021, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines, whose protocol was registered with PROSPERO(CRD42021240684). RESULTS: A total of 9 studies were included. All three laser enucleation techniques had no statistically significant difference in terms of enucleated prostate weight, maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), international prostate symptom score (IPSS), transient UI (TUI), persistent UI (PUI) and early postoperative complications. A shorter enucleation time was associated with the en-bloc technique compared to three technique (MD: -8.26, 95%CI: -12.73--3.79, p = 0.0003), whereas no significant difference was found in en-bloc versus two-lobe technique (MD:0.97,95%CI: -0.30-2.24,p = 0.13) and two-lobe versus three-lobe technique (MD: -3.19, 95%CI: -7.45-1.06, p = 0.14). A higher enucleation rate was associated with the en-bloc and two-lobe technique (MD: 0.05, 95%CI: 0.00-0.10, p = 0.03; MD: 0.09, 95%CI: 0.01-0.17, p = 0.03, respectively). A superior QoL was related to the two-lobe enucleation technique compared to three-lobe technique (MD: 0.22, 95%CI: 0.06-0.39, p = 0.009), whereas no meaningful difference was found in the group of en-bloc versus two-lobe (MD: -0.12, 95%CI: -0.62-0.37, p = 0.62) and group of en-bloc versus three-lobe (MD: -0.14, 95%CI: -0.56-0.29, p = 0.52). CONCLUSIONS: En-bloc and two-lobe laser-based enucleation techniques are feasible and safe alternative to three-lobe technique with comparable surgical outcomes and similar functional outcomes. A superior enucleation efficiency was associated with En-bloc and the two-lobe techniques compared to the three-lobe technique.

Mini-percutaneous nephrolithotomy versus shock wave lithotripsy for the medium-sized renal stones.

INTRODUCTION: The aim of this study was to assess the clinical outcomes of mini-percutaneous nephrolithotomy (Miniperc) and shock wave lithotripsy (SWL) for medium-sized renal stones. EVIDENCE ACQUISITION: A literature search was performed in February 2020 using the Pubmed, Web of Science and Embase. The outcome measurements between two procedures were stone-free rates (SFR), complication rates, operative time, hospitalization stay time, re-treatment rate, auxiliary procedures rate and efficiency quotient. Results were pooled by Review Manager version 5.3 software. EVIDENCE SYNTHESIS: Seven studies on 936 patients (N.=471 for SWL and N.=465 for Miniperc) were included. Miniperc was associated with a higher SFR (OR: 0.25; P<0.00001). In addition, we performed a subgroup analyses for pediatric renal stones and lower pole stones, pooled results also favored Miniperc for higher SFR. SWL was associated with higher auxiliary procedure (OR: 3.32; P<0.00001), higher re-treatment rate (OR: 19.19; P<0.00001) and lower EQ (OR: 0.18; P=0.0003) compared with Miniperc. Besides, SWL was associated with a lower complication rate (OR: 0.36; P=0.0001), shorter operative time (WMD: -34.01; P<0.00001), fluoroscopy time (WMD: -134.48; P<0.00001) and hospital time (WMD: -49.11; P<0.00001) compared with Miniperc. CONCLUSIONS: Miniperc offers a significantly higher SFR, lower auxiliary procedure and re-treatment rate, but SWL was associated with fewer complications.

Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: A New Standard of Urinary Diversion.

Background: To summarize the current evidence on robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) and compare perioperative outcomes and postoperative complications of patients undergoing RARC with extracorporeal urinary diversion (ECUD) and ICUD. Patients and Methods: Through a systematical search of multiple scientific databases in March 2020, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest. Also, we assessed the quality of the relevant evidence according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions. Results: Thirteen studies with 4696 participants were included in this review. No significant differences were found between the ECUD and ICUD in operation time (OT) (mean difference [MD]: -6.45, 95% confidence interval [CI]: -35.20 to 22.30), length of stay (MD: 0.36, 95% CI: -0.81 to 1.54), 30-day overall complications (odds ratio [OR]: 0.92, 95% CI: 0.60-1.41), 30-day minor complications (OR: 1.36, 95% CI: 0.85-2.19), 30-day major complications (OR: 0.70, 95% CI: 0.34-1.43), 90-day overall complications (OR: 1.34, 95% CI: 0.83-2.18), and major complications (OR: 1.03, 95% CI: 0.68-1.57). However, less estimate blood loss (MD: 99.28 mL, 95% CI: 62.59-135.98), lower intraoperative blood transfusion (OR: 1.80, 95% CI: 1.09-2.95), shorter oral intake time (MD: 0.78, 95% CI: 0.43-1.14), and 90-day minor complications (OR: 1.72, 95% CI: 1.08-2.73) were associated with ICUD. The subgroup analysis showed less estimated blood loss (MD: 149.73, 95% CI: 21.33-278.13) and less OT (MD: 32.45, 95% CI: 14.37-50.53) were found in ICUD. Conclusions: The ICUD is a safe and feasible alternative to ECUD, which decreases the need for blood transfusion and reduces 90-day complications. However, further quality studies are needed to evaluate effectiveness of ICUD and its oncologic outcomes, functional outcomes, cost, and the quality of life.

Can 68Ga-prostate specific membrane antigen positron emission tomography/computerized tomography provide an accurate lymph node staging for patients with medium/high risk prostate cancer? A diagnostic meta-analysis.

OBJECTIVE: This article aims to evaluate the diagnostic value of 68Gallium-PSMA positron emission tomography/computerized tomography (68Ga-PSMA PET/CT) for lymph node (LN) staging in patients with prostate cancer (PCa) by a meta-analysis of diagnostic tests. METHODS: We systematically retrieved articles from Web of Science, EMBASE, Cochrane Database, PubMed. The time limit is from the creation of the database until June 2019, and Stata 15 was used for calculation and statistical analyses. RESULTS: Sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR) and 95% confidence intervals (CI) be used to evaluate the diagnostic value. A total of 10 studies were included in our meta-analysis, which included 701 individuals. The results of each consolidated summary are as follows: sensitivity of 0.84 (95% CI 0.55-0.95), specificity of 0.95 (95% CI 0.87-0.98), PLR and NLR was 17.19 (95% CI 6.27, 47.17) and 0.17 (95% CI 0.05-0.56), respectively. DOR of 100 (95% CI 18-545), AUC of 0.97 (95% CI 0.95-0.98). CONCLUSION: Our study demonstrates that 68Ga-PSMA PET/CT has a high overall diagnostic value for LN staging in patients with moderate and high-risk PCa. But our conclusions still require a larger sample size, multi-center prospective randomized controlled trial to verify.

Diagnostic Value of Telomerase Activity in Patients With Bladder Cancer: A Meta-Analysis of Diagnostic Test.

BACKGROUND: This study aimed to evaluate the diagnostic value of telomerase activity (TA) for bladder cancer (BC) by meta-analysis. METHODS: We conducted a systematic search of studies published on PubMed, Embase, and Web of Science up to June 1, 2019. We used Stata 15 and Review Manager 5.3 for calculations and statistical analysis. RESULTS: To evaluate the diagnostic value of TA for BC, we performed a meta-analysis on 22 studies, with a total of 2,867 individuals, including sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR), and 95% confidence intervals (CIs). The pooled parameters were calculated from all studies, and we found a sensitivity of 0.79 (95% CI: 0.72-0.84), a specificity of 0.91 (95% CI: 0.87-0.94), a PLR of 8.91 (95% CI: 5.91-13.43), an NLR of 0.24 (95% CI: 0.15-0.37), a DOR of 37.90 (95% CI: 23.32-61.59), and an AUC of 0.92 (95% CI: 0.90-0.94). We also conducted a subgroup analysis based on the different stages and grades of BC. Results from the subgroup analysis showed that there was no significant difference in TA in either high and low stages of BC, but that low-grade tumors had a lower TA than high-grade tumours. CONCLUSIONS: TA can be used as a potential biomarker for the diagnosis of bladder cancer with its high specificity. Rigorous and high-quality prospective studies are required to verify our conclusion.

Laparoscopic Versus Open Partial Nephrectomy: A Systemic Review and Meta-Analysis of Surgical, Oncological, and Functional Outcomes.

PURPOSE: To summarize and analyze the current evidence about surgical, oncological, and functional outcomes between laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN). MATERIALS AND METHODS: Through a systematical search of multiple scientific databases in March 2020, we performed a systematic review and cumulative meta-analysis. Meanwhile, we assessed the quality of the relevant evidence according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: A total of 26 studies with 8095 patients were included. There was no statistical difference between the LPN and OPN in the terms of operation time (p=0.13), intraoperative complications (p=0.94), recurrence (p=0.56), cancer-specific survival (p=0.72), disease-free survival (p=0.72), and variations of estimated glomerular filtration rate (p=0.31). The LPN group had significantly less estimated blood loss (P<0.00001), lower blood transfusion (p=0.04), shorter length of hospital stay (p<0.00001), lower total (p=0.03) and postoperative complications (p=0.02), higher positive surgical margin (p=0.005), higher overall survival (p<0.00001), and less increased serum creatinine (p=0.002). The subgroup analysis showed that no clinically meaningful differences were found for T1a tumors in terms of operation time (p=0.11) and positive surgical margin (p=0.23). In addition, the subgroup analysis also suggested that less estimated blood loss (p<0.0001) and shorter length of hospital stay (p<0.00001) were associated with the LPN group for T1a tumors. CONCLUSIONS: This meta-analysis revealed that the LPN is a feasible and safe alternative to the OPN with comparable surgical, oncologic, and functional outcomes. However, the results should be applied prudently in the clinic because of the low quality of evidence. Further quality studies are needed to evaluate the effectiveness LPN and its postoperative quality of life compared with OPN.

Can robotic-assisted radical cystectomy provide patients with a smaller trauma and faster recovery period? A systematic review and meta-analysis of comparative trials.

OBJECTIVE: This article explores the differences in the effectiveness and safety of the treatment of bladder cancer (BC) by robotic-assisted radical cystectomy (RARC) and laparoscopic radical cystectomy (LRC). METHODS: A systematic search was performed using databases including Medline, PubMed and Web of Science within a limited period from January 1, 2000, to September 1, 2019. RevMan 5.3 was used for calculation and statistical analyses. RESULTS: We performed meta-analysis on operation time, estimated blood loss, intraoperative blood transfusion, positive surgical margin, oral intake time, length of hospital stay, complication and other indicators, and found that there were no statistically significant differences between LRC and RARC. CONCLUSION: Our meta-analysis results show that LRC and RARC have similar results on the effectiveness and safety of BC. For those medical institutions that cannot perform robot-assisted surgery but are seeking minimally invasive and faster postoperative recovery, LRC is worth considering. However, a larger sample size, more rigorous design and longer follow-up randomized controlled trials are still needed to support our conclusions.

Skp2-mediated degradation of p27 regulates cell cycle progression in compressed human bladder smooth muscle cells.

Bladder outlet obstruction (BOO) results in smooth muscle cell hyperplasia, decreased bladder wall compliance, and lower and upper urinary tract pathology. Mechanical stimulus on detrusor tissue is critical to BOO disease progression. Our previous studies confirm that mechanical stimulus triggers human bladder smooth muscle cell (HBSMC) proliferation. To better understand the signal transduction mechanisms for this process we detected cell cycle machinery of HBSMC (Bose ® Biodynamic, Minnetonka, MN, USA). HBSMCs cultured in scaffolds were subjected to four different pressures (0 cmH2O, 100 cmH2O, 200 cmH2O, and 300 cmH2O) for 24 hours, which were controlled by a BOSE BioDynamic bioreactor. Then we used flow cytometry to examine cell cycle distribution, polymerase chain reaction, and immunoblotting to quantify Skp2, p27, and p21 expression in each group. Additionally, Skp2 was silenced in HBSMCs using small interfering RNA to validate the role of Skp2 in mediating pressure-induced cell cycle progression. Compared with the 0 cmH2O control, HBSMCs in the 200 cmH2O and 300 cmH2O groups exhibited high-level expression of Skp2 gene and low-level expression of p27 protein. However, p21, another downstream signal of Skp2, showed no significant change between groups. In addition, Skp2 silencing abolished increases in cell proliferation induced by pressure. To the best of our knowledge, this is the first report on the functional importance of Skp2 in cyclic hydrodynamic pressure stimulated HBSMC proliferation. The signal transduction mechanism for this process involves p27 as well as p21 signaling pathway.