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Chun-Te Wu,1,2 Yun-Ching Huang,2,3 Wen-Cheng Chen,2,4 Miao-Fen Chen2,4 1Department of Urology, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan; 2Chang Gung University, College of Medicine, Taoyuan, Taiwan; 3Department of Urology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan; 4Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, TaiwanCorrespondence: Miao-Fen ChenDepartment of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, TaiwanEmail miaofen@adm.cgmh.org.twBackground: Bladder-sparing treatment has been developed with the aim of preserving bladder function. However, considerable controversy remains regarding the effectiveness of organ preservation strategies. Accordingly, we investigated factors influencing the prognosis of muscle-invasive bladder cancer (MIBC) patients who received bladder-sparing treatment.Materials and Methods: In the study, we retrospectively reviewed 193 patients who were newly diagnosed with MIBC and received bladder-sparing treatment from 2006 to 2013 in our hospital.Results: The 5-year overall survival, progression-free survival (PFS) and bladder-preservation survival rates after diagnosis were 64.7%, 52.1%, and 64%, respectively. The presence of hydronephrosis, advanced stage and not achieving complete response were associated with a marked reduction in PFS. Treatment with an adequate dose of combined chemoradiotherapy (CCRT) (chemotherapy ≥ 2 cycles combined with radiotherapy dose ≥ 56Gy) significantly improved the complete response (CR), 5-year bladder-preservation survival, and PFS rates, particularly for patients with good performance status. The 5-year bladder-preservation survival rates for CR and non-CR patients were 75%, and 21%, respectively. Furthermore, higher pre-treatment neutrophil-to-lymphocyte ratio (NLR) (≥ 3) and lower hemoglobin (≤ 12) were significantly associated with lower CR rate, increased risk of loco-regional recurrence and reduced bladder-preservation survival rate. Multivariable Cox regression analysis based on different co-variables showed that pretreatment NLR was an independent prognostic factor for PFS when MIBC patients were stratified by clinical stage and the doses of CCRT.Conclusion: In MIBC patients with bladder-sparing treatment, adequate doses of CCRT and low NLR were found to be correlated with better PFS. We suggest the use of NLR as a clinical biomarker for the prognosis of MIBC and guidance of treatment decisions.Keywords: MIBC, bladder-sparing, radiotherapy, recurrence, NLR

Interstitial cystitis/bladder pain syndrome (IC/BPS), which is characterized by bladder pain and irritative voiding symptoms, is a frustrating disease without effective treatment. The cause is still largely not understood, although urothelium ischemia/hypoxia, apoptosis, denudation, and infiltration of inflammatory cells are common histopathological findings. The current uncertainty regarding the etiology and pathology of IC/BPS has a negative impact on its timely and successful treatment; therefore, the development of new treatment modalities is urgently needed. Herein, we present advances in our knowledge on this topic and review the potential application of regenerative medicine for the treatment of IC/BPS. This article provides information on the basic characteristics and clinical evidence of stem cells, platelet-rich plasma (PRP), and low-energy shock waves (LESWs) based on a literature review with a search strategy for articles related to IC/BPS, stem cells, PRP, and LESW published in MEDLINE and PubMed. Stem cells, PRP, and LESW, which modulate inflammatory processes and promote tissue repair, have been proven to improve bladder regeneration, relieve bladder pain, inhibit bladder inflammation, and increase bladder capacity in some preclinical studies. However, clinical studies are still in their infancy. Based on the mechanisms of action of stem cells, PRP, and LESW documented in many preclinical studies, the potential applications of regenerative medicine for the treatment of IC/BPS is an emerging frontier of interest. However, solid evidence from clinical studies remains to be obtained.

Background While epidemiological studies have clearly documented that smoking cessation significantly enhances sexual health, the underlying mechanism remains largely unknown. Thus, we wished to explore possible mechanisms by using a rat model of smoking-associated erectile dysfunction (ED). Methods Forty 8-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats were exposed only to room air (N group). The remaining 30 rats were passively exposed to cigarette smoke over a 12-week period. At the end of 12 weeks, the smoking (S, n=10) group underwent immediate erectile function testing and were sacrificed. The remaining 20 rats were exposed to room air only for 4 (Q4W, n=10) or 8 (Q8W, n=10) weeks and then underwent erectile function testing and sacrifice. Erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP). After blood collection for serum testosterone determination, rats were sacrificed to obtain corporal tissue for immunohistochemistry. Results Mean ICP/MAP ratio was significantly lower in the S group compared to the N and Q8W groups (0.52±0.11, 0.94±0.05, and 0.94±0.12, respectively, P=0.0189). Smooth muscle/collagen ratio was also significantly lower in the S group compared to the N and Q8W groups (11.8±0.94, 17.5±1.82, and 16.4±0.60, respectively, P=0.0008). Oxidative stress and apoptotic indices were significantly higher in the S group compared to the N and Q8W groups. Neuronal and endothelial nitric oxide synthases were significantly less expressed in the S group compared to the N and Q8W groups. Conclusions Smoking cessation is associated with partial recovery of penile hemodynamics in a rat model of smoking associated ED.

Background: Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. Methods: We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan–Meier analyses for survival curves. Results: The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan–Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. Conclusions: Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor.

BACKGROUND/AIM Honokiol is a biphenolic component of the bark of Magnolia, and has been shown to exert several activities, including anti-depressant, anti-emetic, anti-oxidative, anti-thrombotic, anti-angiogenesis, anti-anxiolytic, anti-inflammatory and anti-tumor effects. MATERIALS AND METHODS The anti-tumor activities of honokiol and its synergistic effect with 5-fluorouracil (5-FU) in human urothelial cell carcinoma (UCC) cells were investigated. RESULTS Honokiol significantly suppressed the proliferation of UCC cells in a dose- and time-dependent manner. Moreover, honokiol inhibited the tumorigenesis of UCC cells in vitro. In addition, honokiol induced cell cycle arrest at G0/G1 phase and caused apoptosis of UCC cells through the intrinsic pathway. Importantly, we demonstrated that honokiol potentiated the cytotoxic effect of 5-FU, and displayed a synergistic effect with 5-FU in UCC cells. CONCLUSION Honokiol causes growth inhibition, tumorigenesis suppression, cell cycle arrest, apoptosis, and importantly has a synergistic effect with 5-FU in human UCC cells. Therefore, this agent displays a therapeutic potential for treating human UCC.

In this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. In vitro evaluation confirmed the dose-dependent effect of mTORi, i.e., rapamycin, on fibrotic markers in ureteral component cell lines. Upper ureteral fibrosis was induced by ureteral thermal injury in open surgery, which was followed by insertion of biodegradable stents, with or without rapamycin drug-eluting. Immunohistochemistry and Western blotting were performed 4 weeks after the operation to determine gross anatomy changes, collagen deposition, expression of epithelial–mesenchymal transition markers, including Smad, α-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, α-SMA, and SNAI 1 were increased 28 days after ureteral thermal injury. Treatment with mTORi-eluting biodegradable stents significantly attenuated thermal injury-induced urinary tract obstruction and reduced the level of fibrosis proteins, i.e., type III collagen. TGF-β and EMT signaling pathway markers, Smad and SNAI 1, were significantly modified in DE stent-treated thermal-injury-related ureteral stricture rabbits. These results suggested that intra-ureteral administration of rapamycin by DE stent provides modification of fibrosis signaling pathway, and inhibiting mTOR may result in fibrotic process change.

Background: We investigated the use of a standardized reporting system to study perioperative complications and oncologic outcomes after radical cystectomy in end-stage renal disease (ESRD) patients with bladder cancer. Methods: We reviewed retrospective outcomes in 141 ESRD patients with bladder cancer who underwent radical cystectomy between 2004 and 2015. Complications were graded using the Clavien–Dindo classification system with 0–2 classified as “No Major Complications” and Clavien 3–5 as “Major Complications”. Low-volume surgeons were classified as those performing fewer than nine cases during the study. Fisher’s exact test along with the chi-squared test, two-tailed t tests, logistic regression, and the Cox proportional hazard model were used to evaluate all clinically meaningful covariates. Results: Ninety-nine (99, 70.2%) patients had no major complications, and forty-two (29.8%) patients had major complications. Patients in the major complications group were older, had a higher Charlson comorbidity index (CCI), and had a longer hospitalization duration than those in the no major complications group (all, p < 0.05). Major complications were also more common when the procedure was performed by low-volume surgeons (p = 0.003). In multivariate logistic regression models, CCI ≥ 5 (p = 0.006) and low-volume surgeon (p = 0.004) were independent predictors of major complications. According to multivariate analysis with the Cox hazards regression, male sex, age > 70 years, CCI ≥ 5, bladder cancer stage ≥ 3, lymphovascular invasion, and experiencing major complications were significant poor prognostic factors for overall survival (all, p < 0.05). Conclusions: Accurate reporting of complications is necessary for preoperative counseling, identifying modifiable risk factors, and planning risk mitigation strategies. High comorbidity and low-volume surgeons were interrelated as notable risk factors for major complications. In addition to tumor-related factors, male sex, older age, and major complications significantly influence overall survival.

Regarding localized prostate cancer (PC), questions remain regarding which patients are appropriate candidates for conservative management. Some localized PC was an incidental finding in patients who received transurethral resection of the prostate (TURP) for urinary symptoms. It is known that TURP usually affects the level of prostate-specific antigen (PSA). In the present study, we examined whether changes in PSA levels after TURP possess a predictive value for localized PC. We retrospectively reviewed the clinical data of 846 early-stage PC patients who underwent TURP for urinary symptoms upon diagnosis at our hospital. Of 846 patients, 687 had tumor involvement in TURP specimens, and 362 had post-TURP PSA assessment. Our data revealed that, in addition to low GS and PSA levels at diagnosis, &le, 5% tumor involvement in TURP specimens, greater PSA reduction (&ge, 68%) following TURP, and post-TURP PSA &le, 4 were significantly associated with better progression-free survival (PFS). Survival analysis revealed that the addition of prostate-directed local therapy significantly improved PFS in intermediate- and high-risk groups, but not in the low-risk group. Moreover, in the intermediate-risk group, local therapy improved PFS only for patients who were associated with post-TURP PSA &gt, 4 ng/mL or &lt, 68% PSA reduction following TURP. We also found that local therapy had no obvious improvement in PFS for those with post-TURP &le, 4 ng/mL regardless of pre-TURP PSA. In conclusion, conservative management is considered for patients at low or intermediate risk who have greater PSA reduction following TURP and low post-TURP PSA. Therefore, the levels of PSA following TURP might be helpful for risk stratification and the selection of patients for conservative management.

Non-bacterial prostatitis is an inflammatory disease that is difficult to treat. Oligonucleotide aptamers are well known for their stability and flexibility in conjugating various inflammatory molecules. In this study, we investigated the effects of inflammatory cytokine-targeting aptamers (ICTA), putative neutralizers of TNF-alpha and IL-1 beta activation, on local carrageenan-induced prostate inflammation, allodynia, and hyperalgesia in rats. In vitro evaluation confirmed the binding capability of ICTA. Intraprostatic injection of carrageenan or control vehicle was performed in six-week-old rats, and ICTA (150 &micro, g) or vehicle was administered in the prostate along with carrageenan injection. The von Frey filament test was performed to determine mechanical allodynia, and prostate inflammation was examined seven days after drug administration. Local carrageenan administration resulted in a reduction of the tactile threshold. The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1 beta (b), caspase-1 (casp-1), and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing proteins 1 and 3 (NALP1 and NALP3) in the prostate of rats were increased seven days after carrageenan injection. Treatment with ICTA significantly attenuated the carrageenan-induced hyperalgesia and reduced the elevated levels of proteins including TNF-a and IL-1b in the rats. Apoptosis markers, B-cell lymphoma 2-associated X protein (Bax) and caspase-3, were elevated in ICTA-treated Chronic pelvic pain syndrome (CPPS) rats. These results suggest that ICTA provides protection against local carrageenan-induced enhanced pain sensitivity, and that the neutralization of proinflammatory cytokines may result in inflammatory cell apoptosis.

Background: The aim of this study was to evaluate practicable predictors of 5-year disease-free survival (DFS) and impact of 5-fluorouracil (5-FU)-based adjuvant chemotherapy in stage IIa and IIb colon cancer. Materials and Methods: A total of 1474 patients with stage II colon cancer were enrolled in study. The independent predictors of 5-year DFS and the benefits of adjuvant chemotherapy were analyzed for patients with stage IIa (n = 771) and IIb (n = 703). Results: The incidences of pretreatment anemia, hypoalbuminemia, emergent surgery, and lymphovascular invasion (LVI) corresponded significantly to an advanced T-stage in patients with stage II colon cancer. Although the incidence of surgical morbidity was not different between stage IIa and IIb, stage II patients with hypoalbuminemia had a higher incidence of surgical morbidity than did those with normal serum albumin (17.2% vs. 9.6%, P < 0.001). The co-independent survival predictors in patients with stage IIa and IIb colon cancer were carcinoembryonic antigen (CEA < 5 ng/mL, P = 0.007 and 0.043), serum albumin (≥3.5 g/dL, P < 0.001 and P = 0.025), and nonsurgical morbidity (P < 0.001, both). Suboptimal lymph node harvest (

Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. The outcome of CRC patients remains poor. Thus, a new strategy for CRC treatment is urgently needed. Flavopereirine is a &beta, carboline alkaloid extracted from Geissospermum vellosii, which can reduce the viability of various cancer cells through an unknown mode of action. The aim of the present study was to investigate the functional mechanism and therapeutic potential of flavopereirine on CRC cells in vitro and in vivo. Our data showed that flavopereirine significantly lowered cellular viability, caused intrinsic and extrinsic apoptosis, and induced G2/M-phase cell cycle arrest in CRC cells. Flavopereirine downregulated Janus kinases-signal transducers and activators of transcription (JAKs-STATs) and cellular myelocytomatosis (c-Myc) signaling in CRC cells. In contrast, the enforced expressions of constitutive active STAT3 and c-Myc could not restore flavopereirine-induced viability reduction. Moreover, flavopereirine enhanced P53 expression and phosphorylation in CRC cells. CRC cells with P53 knockout or loss-of-function mutation significantly diminished flavopereirine-mediated viability reduction, indicating that P53 activity plays a major role in flavopereirine-mediated CRC cell growth suppression. Flavopereirine also significantly repressed CRC cell xenograft growth in vivo by upregulating P53 and P21 and inducing apoptosis. In conclusion, flavopereirine-mediated growth suppression in CRC cells depended on the P53-P21, but not the JAKs-STATs-c-Myc signaling pathway. The present study suggests that flavopereirine may be efficacious in the clinical treatment of CRC harboring functional P53 signaling.

Local treatment is known to improve survival in men with locally advanced prostate cancer (LAPC), but the underlying mechanisms remain unclear. In the present study, we examined the role of tumor burden in tumor aggressiveness, as well as the pathway responsible for these changes. We used human and murine prostate cancer cell lines to examine the role of tumor burden in tumor aggressiveness, as well as its correlation with cancer stem cell (CSC) marker levels and IL-6 signaling. Furthermore, 167 prostate cancer biopsy specimens were analyzed in terms of correlations of IL-6 and CD44 levels with clinical patient characteristics. Data from preclinical models showed that larger tumor burden was associated with more aggressive tumor growth associated and increased CD44 expression. Using cellular experiments and orthotopic tumor models, we showed that CD44+ prostate cancer cells have CSC-like properties, enhanced epithelial&ndash, mesenchymal transition (EMT), and a more immunosuppressive microenvironment. There was a significant correlation between IL-6 and CD44 levels based on in vitro testing of clinical samples. Blockade of IL-6/STAT3 signaling attenuated the expression of CD44, CSC-like properties, and aggressive tumor behavior in vitro and in vivo. In conclusion, CD44 expression is significantly associated with tumor aggressiveness in prostate cancer and activation of IL-6 signaling leads to a suitable microenvironment for the induction of CD44 expression. Based on our study, reduced tumor burden was associated with attenuated IL-6 signaling and augmented tumor rejection in the microenvironment, which might mediate the benefit of clinical adoption with aggressive local therapy.

Background Diet is associated with self-reported indices of sexual health. The mechanisms responsible for these changes remain poorly understood. Aim To investigate the hemodynamic and histological impact of dietary change in a rat model of hyperlipidemia-associated erectile dysfunction. Methods 40 2-month old male Sprague–Dawley rats were divided into 4 groups. 10 rats were fed a diet of standard chow and served as negative controls (N group). The remaining 30 age-matched rats were divided at random into 3 groups: (i) high-fat diet for 5 months starting at age 5 months (H group); (ii) high-fat diet for 5 months starting at age 4 months followed by 1 month of standard chow (H+N1M group); and (iii) high-fat diet for 5 months starting at age 2 months followed by 3 months of standard chow (H+N3M group). All rats underwent erectile function testing and sacrifice at age 10 months. Outcomes Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured to evaluate erectile function. Blood samples were collected to measure serum testosterone and lipid levels, and penile tissue specimens were obtained for histological examination. Results Total body weight, low-density lipoprotein, and serum glucose were significantly higher in the H group compared with the N and H+N3M groups. Serum high-density lipoprotein level was significantly lower in the H group compared with the N and H+N3M groups. The mean ICP/MAP ratio was significantly lower in the H group compared with the N and H+N3M groups (0.33 ± 0.05 vs 0.79 ± 0.07 vs 0.73 ± 0.13; P < .05 for both). Markers for intracorporal neuronal nitric oxide synthase and endothelial cells were more weakly expressed in the H group compared with the N and H+N3M groups. There was no significant difference in smooth muscle content among the groups. Mean cavernosal oxidative stress and the apoptotic index were significantly higher in the H group compared with the N and H+N3M groups. No significant between-group differences were noted with respect to serum testosterone; the H group had significantly higher serum glucose and low-density lipoprotein levels, effects that were partially mitigated in the H +N1M and H+N3M groups. Clinical Translation Administration of a healthy diet is associated with normalization of functional and histological penile defects associated with a high-fat diet. Strengths & Limitations Metabolic changes were clearly linked to functional improvements in penile blood flow. Differences between rat and human lipoprotein metabolism are a limitation of this study. Conclusion Dietary changes may have positive effects on penile hemodynamics in a rat model of hyperlipidemia-associated erectile dysfunction.

Diabetes is usually asymptomatic in its early stage. Early diagnosis may improve outcomes by enabling initiation of treatment before end organ damage has progressed. The aim of this study was to determine whether the clinical sign of phimosis with preputial fissures is predictive of type 2 diabetes in patients not previously diagnosed with diabetes. Twenty-eight patients with acquired phimosis and preputial fissures were collected prospectively. Twenty-eight controls with acquired phimosis without preputial fissures were selected. Statistically significant differences were found in body mass index, random plasma glucose, glucosuria and glycosylated haemoglobin levels, but not in age, family history of diabetes, hypertension and classical hyperglycaemic symptoms. Diabetes was confirmed in all 28 patients in the preputial fissures group, but only 2 (7.1%) patients in the non-preputial fissures group (p < 0.0001). In conclusion, phimosis with preputial fissures may be a specific sign of undiagnosed diabetes mellitus.

The stress-upregulated catecholamines-activated β1- and β2-adrenergic receptors (β1/2-ARs) have been shown to accelerate the progression of cancers such as colorectal cancer (CRC). We investigated the underlying mechanism of the inhibition of β1/2-ARs signaling for the treatment of CRC and elucidated the significance of β2-AR expression in CRC in vitro and in clinical samples. The impacts of β1/2-AR antagonists in CRC in vitro and CRC-xenograft in vivo were examined. We found that repression of β2-AR but not β1-AR signaling selectively suppressed cell viability, induced G1-phase cell cycle arrest, caused both intrinsic and extrinsic pathways-mediated apoptosis of specific CRC cells and inhibited CRC-xenograft growth in vivo. Moreover, the expression of β2-AR was not consistent with the progression of CRC in vitro or in clinical samples. Our data evidence that the expression profiles, signaling, and blockage of β2-AR have a unique pattern in CRC comparing to other cancers. β2-AR antagonism selectively suppresses the growth of CRC accompanying active β2-AR signaling, which potentially carries wild-type KRAS, in vitro and in vivo via the inhibition of β2-AR transactivated EFGR-Akt/ERK1/2 signaling pathway. Thus, β2-AR blockage might be a potential therapeutic strategy for combating the progressions of β2-AR-dependent CRC. J. Cell. Physiol. 231: 459-472, 2016. © 2015 Wiley Periodicals, Inc.

The aim of the present study was to investigate whether unintentional body weight loss (BWL) provides additional clinical information in terms of tumor progression and prognosis in non-metastatic colon cancer. In the present study, a total of 2,406 consecutive colon cancer patients without metastasis were retrospectively enrolled. Unintentional BWL was defined as loss of >5% of body weight within the last 6–12 months, or defined subjectively upon fulfillment of at least two of the following: Evidence of change in clothing size and corroboration of the reported weight loss by family or friend. This category was recorded as present (‘with’) or absent (‘without’). Logistic regression analysis was performed to determine the correlation between BWL and the tumor characteristics and post-operative outcomes of patients with colon cancer. The Cox regression model was used to determine the association of BWL with long-term survival of colon cancer patients. A significant association between BWL and tumor location [right vs. left: Odds ratio (OR)=1.62; P

Complete urinary tract extirpation (CUTE) is a complex procedure with substantial risk for perioperative complications. The association between clinical characteristics and the risk of major postoperative complications has not been systematically investigated. The aim of this study was to analyze the incidence and risks for major perioperative complications after CUTE. Respective chart review of 81 patients with urothelial carcinoma (UC) who were treated with one-stage CUTE between January 2004 and December 2015. Fisher’s exact test with Chi square and two-tailed t test were used in categorical and continuous variables, respectively. Univariable and multivariable logistic regression models were used to evaluate the probability of major complications. In this population, 53 (65.4%) patients had Clavien grade 0–2 complications (‘no major complications’) and 28 (34.6%) patients had Clavien grade 3–5 complications (‘major complications’). Compared with the major complications group, patients in the no major complications group were younger, had lower Charlson Comorbidity Index (CCI), higher preoperative serum albumin, and shorter duration of hospitalization (p

With the rapid social, technological and industrial development, globalization, and the formation of the M-shaped society, the wealth disparity has been widened, and the ability to cope with pressure has become increasingly important. Community is a residential area where people and land coexist, and the humanistic development of communities is the miniature of social development. As people are confronted with such problems of long-term migration of rural residents and aging, art can help the elderly activate mind, alleviate pressure, enhance spiritual motivation, and accelerate the humanistic development of communities.

Stem cells (SCs) have been investigated for the treatment of erectile dysfunction (ED).This review covers key disease targets and all 33 preclinical studies, including their use of SC types, animal models, transplantation routes, and outcome assessment methods.In the past one and half years there have been more stem-cell-for-erectile-dysfunction studies than the prior 8 years combined. These new studies tend to use combinatory treatment approaches by modifying or supplementing SCs with angiogenic or neurotrophic genes or proteins. However, when considering all risks and benefits, these combinatory approaches do not seem more advantageous than single-SC approaches. Another trend is the choice of transplantation routes other than the standard intracavernous (IC) injection. However, with the exception of intravenous injection, these new transplantation approaches are more cumbersome than IC injection and yet offer no evidence of producing better outcomes. In contrast to these variations, a consensus among these studies is the suggestion that paracrine action, as opposed to cellular differentiation, is the principal therapeutic mechanism. In conclusion, IC injection of a single SC type should be the choice protocol for initial clinical trials, and this is clearly the case with two clinical trials that are currently recruiting patients.

Basic studies have proven that cranberries may prevent urinary tract infections through changing the adhesiveness of Escherichia coli (E. coli) to urothelial cells. Various cranberry preparations, including extract powder, capsules, and juice, have been shown to be effective in clinical and epidemiological research. Because cranberries are most commonly consumed as juice in a diluted concentration, the aim of this study was to investigate whether the equivalent daily dose of cranberry juice is sufficient to modify host urine to change the uropathogenicity of E. coli. Urine from rats taking an equivalent daily dose of cranberry juice has been shown to decrease the capability of E. coli in hemagglutination, urothelium adhesion, nematode killing, and biofilm formation. All these changes occurred after E. coli was incubated in cranberry metabolite-containing urine, defined as urine opsonization. Urine opsonization of E. coli resulted in 40.9 % (p = 0.0038) decrease in hemagglutination ability, 66.7 % (p = 0.0181) decrease in urothelium adhesiveness, 16.7 % (p = 0.0004) increase in the 50 % lethal time in killing nematodes, and 53.9 % (p = 5.9 × 10−4) decrease in biofilm formation. Thus, an equivalent daily dose of cranberry juice should be considered sufficiently potent to demonstrate urine opsonization in E. coli.

Background/aim Evodiamine, an indole alkaloid derived from Evodia rutaecarpa, exhibits pharmacological activities including vasodilatation, analgesia, anti-cardiovascular disease, anti-Alzheimer's disease, anti-inflammation, and anti-tumor activity. Materials and methods This study analyzes the anti-tumor effects of evodiamine on cellular growth, tumorigenesis, cell cycle and apoptosis induction of human urothelial cell carcinoma (UCC) cells. Results The present study showed that evodiamine significantly inhibited the proliferation of UCC cells in a dose- and time-dependent manner. Also, evodiamine suppressed the tumorigenesis of UCC cells in vitro. Moreover, evodiamine caused G2/M cell-cycle arrest and induced caspase-dependent apoptosis in UCC cells. Finally, we demonstrated that evodiamine exhibits better cytotoxic than 5-fluorouracil, a clinical chemotherapeutic drug, for UCC cells. Conclusion Evodiamine induces growth inhibition, tumorigenesis suppression, cell-cycle arrest, and apoptosis induction in human UCC cells. Therefore, this agent displays a therapeutic potential for treating human UCC cells and is worthy for further investigation.

There is relatively little literature on adjuvant radiotherapy after radical nephroureterectomy with bladder cuff excision (RNU) for patients with upper tract urothelial carcinoma (UTUC). This study was designed to determine the efficacy of adjuvant radiotherapy for patients with pT3N0M0 UTUC. We retrospectively reviewed 198 patients treated with RNU between December 2001 and January 2015. Postoperative radiotherapy was administered in 40 (20.2%) of patients. Patients who received radiotherapy were younger than those that did not (65.2 vs. 70.5 years, p = 0.023). With median follow up of 29.1 months, Kaplan-Meier analysis with the log-rank test demonstrated no significant differences between those omitting vs receiving adjuvant radiotherapy in regards to 2-year rates of overall survival (72.0% vs. 73.4%, p = 0.979), cancer-specific survival (73.2% vs. 75.3%, p = 0.844), and recurrence-free survival (61.2% vs. 66.3%, p = 0.742). However, in multivariable analysis with Cox regression, young age, absence of chronic kidney disease, negative lymphovascular invasion, negative surgical margin, and adjuvant chemotherapy were also associated with better cancer-specific survival. In conclusion, adjuvant radiotherapy did not offer any significant benefit in terms of overall, cancer-specific, and recurrence-free survivals in patients with pT3N0M0 UTUC after RNU. More effective systemic adjuvant chemotherapy is necessary to improve the outcome of these patients.

INTRODUCTION AND OBJECTIVES: Radium Ra 223 dichloride (Ra-223), an intravenous alpha-emitting radioisotope, is a calcium mimetic, forming complexes with hydroxyapatite at sites of bone metastasis for castration-resistant prostate cancer (mCRPC) patients. Abiraterone Acetate (AA), an oral androgen biosynthesis inhibitor, decreases serum testosterone for mCRPC patients. This study evaluates safety and quality of life of concurrent use of these FDA approved CRPC therapies, and is the largest cohort of subjects reported to date. METHODS: This open-label, phase II study (NCT02097303), enrolled subjects with symptomatic bone mCRPC. Subjects were assessed at baseline, day 1 of each of 6 cycles and 30 days post final Ra-223 treatment. Primary objectives were quality of life and bone pain measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Bone Pain Index Short Form (BPI-SF). Secondary objectives were adverse events (AE), disease progression, performance status, total alkaline phosphatase, prostate specific antigen, skeletal related events, and more antineoplastic therapy. Safety data were analyzed for all with >/1⁄4 1 infusion of Ra-223. RESULTS: 31 of 37 enrolled subjects completed the study and received Ra-223 every 4 weeks x 6 doses. + 28/37 received AA 1000 mg QD; 3/37 required dose reduction. All subjects received prednisone 5 mg BID. Median AA use before first Ra-223 dose was 31 days [95% CI 24.2-37.8]. Subjects had significant improvements in FACT-P Prostate subscales and no significant increases in pain. They reported significant pain relief from treatment. 19/31 had radiographic disease improvement or stability. Secondary endpoints also showed benefit of the combined treatment. ECOG scores remained stable. Subjects reported 72 AEs related to treatment; 44, 26, and 2 were grade 1, 2, and 3, respectively. Common AEs were fatigue and gastrointestinal issues. 4 SAEs were reported; 1 abdominal pain possibly related to AA and 3 non-related to treatment, including one death. CONCLUSIONS: This prospective trial of Radium 223 and Abiraterone Acetate confirms an overall improvement in Quality of Life, and demonstrates tolerability of synergistic use of the approved mCRPC agents. Source of Funding: Bayer Healthcare Pharmaceuticals, Inc. Statistical Analysis Provided By: Department of Data Management & Statistical Analysis, American Urological Association.

BACKGROUND The mechanism of non-bacterial chronic prostatitis (CP/CPPS) has long been investigated but remains unclear. Under the hypothesis that abnormal response of innate immunity may be a cause of CP/CPPS, this study evaluated inflammasome, as part of innate immunity, and its effects on persist inflammation and CP/CPPS. METHODS Carrageenan was used to induce CP/CPPS in a rat animal model. After confirming tactile hyper-algesia in the rats, their local prostate inflammation status, and inflammasome expression were determined. The amount of inflammasome and its downstream protein was checked, along with prostate localization. Chlorogenic acid (CHA), an active ingredient of Chinese herbal remedy for CP/CPPS treatment, was used as treatment. RESULTS The rats had CP/CPPS once scrotal static tactile allodynia developed and CHA treatment relieved the scrotal hypersensitivity. Downstream inflammasome proteins like IL-1β and caspase 1 increased within the prostate and decreased with CHA treatment. Inflammasome, NALP1 but not NALP3, was significantly increased in the prostate glandular endothelial cells. Treatment with CHA also changed the distribution pattern of NALP1 in the prostate. CONCLUSIONS There is a close relationship between activation of inflammasome and patho-physiologic changes of CP/CPSS in rats. Increased inflammasome may be a possible mechanism of CP/CPPS and clinically active regimen may inhibit the inflammasome-related pathway. This provides a new therapeutic rationale and approach for CP/CPPS treatment. Prostate 73: 391–397, 2013. © 2012 Wiley Periodicals, Inc.

Study Type – Aetiology (case control) Level of Evidence 3b What’s known on the subject? and what does the study add? Increased cavernous smooth muscle content has been repeatedly observed in rat models of hyperlipidaemia – associated erectile dysfunction. This study shows that the increased smooth muscle content is due to hyperplasia. OBJECTIVE • To investigate the structural changes, including possible smooth muscle hyperplasia, in the penis of a hyperlipidaemia-associated erectile dysfunction (ED) animal model. MATERIALS AND METHODS • Hyperlipidaemia was induced in rats through a high-fat diet. • Penile tissues of normal and hyperlipidaemic rats were stained with Alexa-488-conjugated phalloidin and/or with antibodies against rat endothelial cell antigen, neuronal nitric oxide synthase (nNOS), and collagen type IV (Col-IV) before image and statistical analyses were carried out. • The main outcome measures were the smooth muscle, endothelial, Col-IV and nNOS content of the corpus cavernosum. RESULTS • Phalloidin intensely stained all smooth muscle in the penis, revealing the circular and longitudinal components of cavernous smooth muscle (CSM). • The CSM content was significantly higher in the hyperlipidaemic than in the normal rats (P < 0.05). • Cell numbers in both circular and longitudinal CSM were significantly higher in the hyperlipidaemic than in the normal rats (P < 0.05). • Cavernous endothelial content was significantly lower in hyperlipidaemic than in normal rats (P < 0.05). • nNOS-positive nerves within the dorsal nerves, around the dorsal arteries, and in the corpora cavernosa were all significantly lower in the hyperlipidaemic than in the normal rats (P < 0.05). CONCLUSIONS • Hyperlipidaemia is associated with reduced nNOS-positive nerves, reduced endothelium, and increased CSM in the penis. • The increased CSM is attributable to hyperplasia. • These structural changes may explain why hyperlipidaemic men are more likely to develop ED.