The impact of secondhand smoke on the development of kidney stone disease is not inferior to that of smoking: a longitudinal cohort study.

BACKGROUND: Tobacco use and secondhand smoke (SHS) are risk factors of kidney stone disease (KSD). The hypothesis is that tobacco produces chemicals that increase oxidative stress and vasopressin, which leads to decreased urine output, and contributes to stone formation. The aim of this study was to examine the effects of smoking and SHS on the development of KSD. MATERIALS AND METHODS: We analyzed a total of 25,256 volunteers with no history of KSD participated in the Taiwan Biobank. The presence of underlying and follow-up KSD was surveyed by a self-administrated questionnaire. They were classified into three groups on the basis of smoking and SHS exposure, accessed with survey questionnaires; never-smokers with no SHS exposure, never-smokers with SHS exposure and ever-smokers groups. RESULTS: KSD was noted in 352 (2.0%), 50 (3.3%) and 240 (4.1%) subjects in the never-smokers with no SHS exposure, never-smokers with SHS exposure and ever-smokers groups, respectively, with a mean follow-up of 4 years. The odds ratio (OR) of KSD was higher in the never-smokers with SHS exposure (OR, 1.622; 95% confidence interval [95% CI], 1.225 to 2.255) and ever-smokers groups (OR, 1.282; 95% CI, 1.044 to 1.574) than in the never-smokers with no SHS exposure group after adjustment of confounders. In addition, never-smokers with SHS exposure had similar effects on the development of KSD than ever-smokers (OR, 1.223; 95% CI, 0.852 to 1.756). CONCLUSION: Our study suggests that both smoking and SHS are a risk factor for developing KSD and that the impact of SHS is not inferior to that of smoking. TRIAL REGISTRATION: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-E(I)-20,210,058).

The association between menopause, postmenopausal hormone therapy, and kidney stone disease in Taiwanese women.

PURPOSE: The association between menopause, postmenopausal hormone therapy, and kidney stone disease has long been a topic of discussion and is still unclear. Moreover, most previous research has focused on Caucasians. Therefore, we aimed to explore this issue in an Asian population. METHODS: In this cross-sectional study, we enrolled female participants aged between 30 and 70 years from the Taiwan Biobank. The presence of kidney stone disease (KSD) was defined through a self-reported questionnaire. The participants were divided into two groups according to the presence of menopause; premenopausal and postmenopausal groups. The associations among menopause, postmenopausal hormone therapy, and KSD were examined using binary logistic regression models. RESULTS: A total of 17,460 women with available information were recruited, including 5976 in the premenopausal group and 11,484 in the postmenopausal group. Compared to the premenopausal group, the postmenopausal group had a significantly higher prevalence of KSD (3% vs. 6%). The odds ratio for KSD was higher in the postmenopausal group than in the premenopausal group (odds ratio = 1.50; 95% confidence interval = 1.17-1.92) after adjusting for confounders. We also examined associations between the type of menopause (natural and surgical) and KSD, and found that both types of menopause were associated with KSD in age-adjusted and multivariable models. Compared with those who had never received postmenopausal hormone therapy, those who had received postmenopausal hormone therapy were not associated with a higher risk of KSD. CONCLUSIONS: Our study suggests that natural and surgical menopause were associated with KSD. However, we found no association between the postmenopausal hormone therapy and KSD in the postmenopausal women.

The Safety and Efficacy of Vela Laser En-Bloc Endoscopic Resection versus Conventional Transurethral Resection of Bladder Tumor-A Single Center Experience.

(1) Background: The current gold standard treatment of bladder cancer is conventional transurethral resection of the bladder tumor (CTURBT) using monopolar or bipolar resectoscopes. Laser en-bloc resection of the bladder tumor (LERBT) could achieve a higher quality of the specimen, reduce perioperative complications, and decrease the recurrence rate. Here, we compare the efficacy and safety of en-bloc Vela laser resection versus the conventional monopolar/bipolar resection; (2) Methods: A total of 100 clinically cT1-2 patients with bladder cancer were retrospectively reviewed in this study. Among these patients, 50 patients received LERBT, and 50 patients received CTURBT. The baseline characteristics, operation variables, and clinical outcomes were collected. The primary performance was the presence of muscle layer in the specimen. Perioperative complications and recurrence-free survival (RFS) were also compared. Independent t-test, Chi-square test, Kaplan-Meier curves, and the Cox-regression model were used in the analysis; (3) Results: The median age of the patients in the laser and resectoscope groups was 69.2 and 68.0 years old, respectively. The statistical difference in the presence of the detrusor muscle was 92.0% in the laser group and 70.0% in the CTURBT group (p = 0.005). A lower incidence of bladder perforation (p = 0.041) and major surgical complications (p = 0.046) in the LEBRT group was observed. We found no differences in operation duration, catheterization time, and hospitalization time after adjustment. Additionally, there was no statistical difference in RFS after a median follow-up time of 25 months; (4) Conclusions: Endoscopic laser en-bloc resection of bladder tumor with Vela laser is an effective method with higher muscle inclusion rate and fewer complications.

Betel Nut Chewing Is Associated with the Risk of Kidney Stone Disease.

(1) Background: Betel nut chewing injures bodily health. Although, the relationship between betel nut chewing and kidney stone disease (KSD) is unknown. (2) Methods: We analyzed 43,636 men from Taiwan Biobank. We divided them into two groups on the status of betel nut chewing, the never-chewer and ever-chewer groups. Self-reported diagnosed KSD was defined as the subject's medical history of KSD in the questionnaire. Logistic regression was used to analyze the association of betel nut chewing and the risk of KSD. (3) Results: The mean age of subjects in the present study was 50 years, and 16% were ever-chewers. KSD was observed in 3759 (10.3%) and 894 (12.6%) participants in the group of never-chewer and ever-chewer groups, respectively. Higher risk of KSD was found in participants with betel nut chewing compared with to without betel nut chewing (odds ratio (OR), 1.094; 95% confidence interval (95% CI), 1.001 to 1.196). Furthermore, the daily amounts of betel nut chewing >30 quids was associated with a more than 1.5-fold increase (OR, 1.571; 95% CI, 1.186 to 2.079) in the odds of KSD; (4) Conclusions: Our study suggests that betel nut chewing is associated with the risk of KSD and warrants further attention to this problem.

Genetic Polymorphisms of MnSOD Modify the Impacts of Environmental Melamine on Oxidative Stress and Early Kidney Injury in Calcium Urolithiasis Patients.

Environmental melamine exposure increases the risks of oxidative stress and early kidney injury. Manganese superoxide dismutase (MnSOD), glutathione peroxidase, and catalase can protect the kidneys against oxidative stress and maintain normal function. We evaluated whether their single-nucleotide polymorphisms (SNPs) could modify melamine's effects. A total of 302 patients diagnosed with calcium urolithiasis were enrolled. All patients provided one-spot overnight urine samples to measure their melamine levels, urinary biomarkers of oxidative stress and renal tubular injury. Median values were used to dichotomize levels into high and low. Subjects carrying the T allele of rs4880 and high melamine levels had 3.60 times greater risk of high malondialdehyde levels than those carrying the C allele of rs4880 and low melamine levels after adjustment. Subjects carrying the G allele of rs5746136 and high melamine levels had 1.73 times greater risk of high N-Acetyl-ß-d-glucosaminidase levels than those carrying the A allele of rs5746136 and low melamine levels. In conclusion, the SNPs of MnSOD, rs4880 and rs5746136, influence the risk of oxidative stress and renal tubular injury, respectively, in calcium urolithiasis patients. In the context of high urinary melamine levels, their effects on oxidative stress and renal tubular injury were further increased.

Metabolic Syndrome Increases the Risk of Kidney Stone Disease: A Cross-Sectional and Longitudinal Cohort Study.

We aimed to examine the association between metabolic syndrome and the risk of kidney stone development in a large-scale community-based cohort. A total of 121,579 participants enrolled in the Taiwan Biobank were analyzed. They were divided into two groups on the basis of presence of metabolic syndrome. The presence of kidney stone disease was defined by self-reported history of kidney stones. The mean age of participants was 50 years old, and self-reported kidney stones were observed in 3446 (10%) and 4292 (5%) participants with metabolic syndrome and without metabolic syndrome, respectively. Higher prevalence of kidney stone disease was found in participants with metabolic syndrome compared to those without metabolic syndrome (odds ratio (OR), 1.32; 95% confidence interval (95% CI), 1.25 to 1.39). In addition, the risk of incident kidney stone development was analyzed in a longitudinal cohort of 25,263 participants without kidney stones at baseline during a mean follow-up of 47 months. Multivariable Cox regression analysis revealed that the risk for incident kidney stone disease was higher in participants with metabolic syndrome than those without metabolic syndrome (hazard ratio, 1.24; 95% CI, 1.04 to 1.49). Our study suggests that metabolic syndrome does increase the risk of kidney stones.

Therapeutic effect of Low intensity Extracorporeal Shock Wave Therapy (Li-ESWT) on diabetic bladder dysfunction in a rat model.

Objectives: Low intensity extracorporeal shock wave therapy (Li-ESWT) has proven to be effective and safe for the treatment of various urological disorders including erectile dysfunction and chronic pelvic pain syndrome. In this study, we elucidated the therapeutic effect and possible mechanisms of Li-ESWT on diabetic bladder dysfunction (DBD) in a rat model. Materials and Methods: In all, thirty-two female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus (DM) control, and DM Li-ESWT. The two DM groups were given high fat diets for one month, followed by 2 intraperitoneal injections of streptozotocin (STZ) 30 mg/kg separated by one week. Body weight and fasting blood glucose were monitored every week. Only rats with fasting blood glucose 140 mg/dL or more were considered diabetic and used in the subsequent portions of the study. The Li-ESWTs were applied toward the pelvis of the rats twice a week for 4 weeks with energy flux density (EFD) 0.02 mJ/mm2, 500 shocks, at 3Hz. All rats underwent plasma insulin tolerance test, conscious cystometry, leak-point pressure (LPP) assessment, and immunohistochemical studies. Results: DM groups had significantly lower insulin sensitivity and higher body weight. Conscious cystometry also revealed voiding dysfunctions. In the DM Li-ESWT group, the rats had significantly improved voiding functions that were reflected in longer micturition intervals and higher LPP compared to DM control. Immunofluorescence in DM control groups showed increased tyrosine hydroxylase (TH) expression and decreased neuronal nitric oxide synthase (nNOS) expression in the longitudinal urethral smooth muscles. Besides, rats had dilations and deformities of suburothelium capillary network of the bladder, revealing the deterioration of the nerve function of the urethra and destruction of the vascularization of the bladder. However, the DM Li-ESWT group exhibited recovery of the nerve expression of the urethra and vascularization of bladder. Conclusions: Li-ESWT ameliorates the bladder dysfunction and urinary continence in the DBD rat model, reflected in restoration of the nerve expression of the urethra and the vascularization of the bladder. Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.

Herpes zoster and the subsequent risk of prostate cancer in an Asian population: A nationwide population-based cohort study.

It has been suggested that herpes zoster may increase the risk of subsequent prostate cancer (PCa). We aimed to assess the risk of PCa following herpes zoster by the population-based follow-up study.This is a retrospective study and data are from the Taiwan National Health Insurance Research Database (NHIRD). The study cohort comprised all patients with a diagnosis of herpes zoster (International Classification of Diseases, 9th Revision, Clinical Modification code 053.0-053.9) and followed for PCa from 1997 to 2013 (n = 11,376). Subjects younger than 20 years of age were excluded. The match-control cohort was identified from the Registry of Beneficiaries of the NHIRD and randomly selected by matching with the study cohort at a 3:1 ratio based on age (every 5-year span), and year of herpes zoster diagnosis (n = 34,128). We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) for subsequent PCa, after controlling for potential cormobidities.Men with and without herpes zoster had similar age and comorbidity distributions. Among the 45,504 sampled patients, 1011 (2.22%) developed PCa during the 10 years of follow-up, 276 (2.43%) from the study cohort and 735 (2.15%) from the match-control cohort and the incidence rate was 3.13 and 2.72 per 1000 person years respectively. Patients with herpes zoster were more likely to develop PCa than patients in the match-control cohort (HR = 1.15; 95% confidence interval (CI) = 1.00-1.32, P value = .045). After adjusting for age and comorbidities, herpes zoster was associated with a 1.15 increased risk of PCa (adjusted HR = 1.15, 95% CI = 0.99-1.32, P value = .054).Our study indicates that preceding herpes zoster infection is a suggestive risk marker for subsequent PCa after controlling for potential confounders. Further prospective studies are needed to determine the relationship between herpes zoster and PCa.

Lower urinary tract symptoms-Benign prostatic hyperplasia may increase the risk of subsequent inguinal hernia in a Taiwanese population: A nationwide population-Based cohort study.

INTRODUCTION & OBJECTIVES: It has been suggested that lower urinary tract symptoms-benign prostatic hyperplasia (LUTS-BPH) may be a risk factor for inguinal hernia (IH). The aim of this study was to examine the emergence of a subsequent IH diagnosis in men with and without LUTS-BPH. METHODS: From a database derived from the National Health Insurance Program covering 99% of the population in Taiwan, 22,310 men with LUTS-BPH and 22,310 matched men without LUTS-BPH were identified and followed for IH from 1997 to 2013. Both IH and LUTS-BPH were defined by the ninth revision of the International Classification of Diseases code (ICD9). Subjects younger than 20 years of age and with IH diagnosed before the index date were excluded. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for subsequent IH, controlling for potential confounders. RESULTS: Men with and without LUTS-BPH had similar age and comorbidity distributions. During the 10 years of follow-up, 1,303 (5.84%) men with LUTS-BPH and 735 (2.53%) men without LUTS-BPH developed IH. The mean time to IH was 4.02 years and 4.44 years, respectively. After adjusting for age and comorbidities, LUTS-BPH was associated with a two-fold increased risk of IH (HR:2.25, 95% CI = 2.04-2.49). CONCLUSION: This nation-wide population-based cohort study showed that LUTS-BPH increased the risk of subsequent IH in a Taiwanese Population.

The effects of microenergy acoustic pulses on an animal model of obesity-associated stress urinary incontinence. Part 1: Functional and histologic studies.

AIM: Obesity is a strong independent risk factor for urinary incontinence. Effective therapeutic approaches for obesity-associated stress urinary incontinence (OA-SUI) are lacking as the mechanisms remain unclear. The aim of our study is to explore the impacts of microenergy acoustic pulse (MAP) therapy on urethral and pelvic floor muscle structure and function in female lean and fatty rats. METHODS: A total 24 Zucker fatty (ZF) and 24 Zucker lean (ZL) female 24-week-old rats were grouped into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. For MAP treatment, 500 pulses were delivered at an energy level of 0.033 mJ/mm 2 and a frequency of 3 Hz and were applied twice a week for 4 weeks. After a 1-week washout, all rats underwent conscious cystometry and leak-point pressure (LPP) measurements followed by ex vivo organ-bath assay and histological study. RESULTS: ZF rats had lower LPP as compared to ZL rats, and MAP treatment significantly improved LPP in ZF rats (P < .05). Impaired muscle contractile activity (MCA) in organ-bath study was noted in ZF rats. MAP treatment significantly increased MCA in ZF rats (P < .05) and also increased the thickness of the striated muscle layer and the number of neuromuscular junctions (NMJs). In situ, MAP activated muscle satellite cells significantly (P < .05). CONCLUSIONS: Obesity impairs the function of both the urethral sphincter and the pelvic floor and leads to atrophy and distortion of the striated muscle in obese female rats. These issues contribute to OA-SUI. MAP improves continence by stimulating muscle regeneration and nerve innervation as well as by activating satellite cells.

Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury.

BACKGROUND: Erectile dysfunction (ED) caused by pelvic neurovascular injury (PNVI) is often refractory to treatment. In many cases, erectogenic therapy is administered in a delayed fashion. AIM: To evaluate penile hemodynamic effects and histologic changes associated with delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) after PNVI ED in a rat model. We visualized images using immunofluorescence and 3-dimensional imaging of solvent-cleared organs (3DISCO), a novel imaging technique. METHODS: A total of 32 Sprague-Dawley male rats aged 12 weeks were divided equally into 4 groups: sham surgery as normal controls (NC), PNVI controls (PC), PNVI with very-low-energy Li-ESWT (PVL), and PNVI with low-energy Li-ESWT (PL). Bilateral cavernous nerve crush and internal pudendal bundle ligation were performed in the 3 PNVI groups. Li-ESWT was administered twice a week for 4 weeks in the PL and PVL groups starting at 4 weeks after PNVI. OUTCOMES: Intracavernous pressure (ICP) studies (normalized to mean arterial pressure [MAP]) were conducted in all subject animals. After testing, tissue was harvested for immunofluorescence staining and 3DISCO analysis. RESULTS: Mean ICP/MAP was lower in PC animals compared with NC animals (0.37 ± 0.03 vs 0.91 ± 0.03, respectively; P = .001). The ICP/MAP ratio was significantly higher in PVL and PL animals (0.66 ± 0.07 and 0.82 ± 0.05, respectively) compared with PC animals (P = .002 and .001, respectively). Detailed microstructures and trajectories of nerves and vessels were identified with immunofluorescence and 3DISCO. The PC group had lower density of nerves, axons, neuronal nitric oxide synthase-positive nerves, and Schwann cells in the dorsal penis. Animals in the PL group had significantly higher expression of all of these markers compared with PC animals. CLINICAL IMPLICATIONS: Li-EWST may have utility in the management of severe ED related to PNVI from severe pelvic injury or radical pelvic surgeries, even when administered in a delayed fashion. STRENGTH & LIMITATIONS: This study of a severe ED phenotype involved treatment administered in a delayed fashion, which is more consistent with how therapy likely would be delivered in a real-world clinical context. Moreover, because the treatment commenced at 4 weeks after injury, when nerve and tissue atrophy have already occurred, the results imply that Li-ESWT can be used for regenerative therapy. Additional studies on dose optimization and treatment interval are needed to inform the design of human clinical trials. CONCLUSION: Li-ESWT ameliorates the negative functional and histologic effects of severe pelvic neurovascular injury in a rat model system. 3DISCO provides high-resolution images of neuroanatomy and neural regeneration. Wang HS, Ruan Y, Banie L, et al. Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury. J Sex Med 2019;16:17-26.

Microenergy acoustic pulses induced myogenesis of urethral striated muscle stem/progenitor cells.

BACKGROUND: Stress urinary incontinence (SUI) is a common disorder with high prevalence in women across their life span, but there are no non-surgical curative options for the condition. Stem cell-based therapy, especially endogenous stem cell therapy may be a potential treatment method for SUI. The aims of this study are to identify, isolate, and assay the function of urethral striated muscle derived stem/progenitor cells (uMDSCs) and to assess uMDSC response to microenergy acoustic pulses (MAP). METHODS: Urethral striated muscle was identified utilizing 3D imaging of solvent organs (3DISCO) and immunofluorescence (IF). uMDSCs were isolated and purified from Zucker Lean (ZL) (ZUC-LEAN) (ZUC-Leprfa 186) rats, with magnetic-activated cell sorting (MACS) and pre-plating methods. The stemness and differentiation potential of the uMDSCs were measured by cell proliferation, EdU, flow cytometry, IF, and Western blot. RESULTS: Comparison of the cell proliferation assays between MACS and pre-plating reveals the advantage of MACS over pre-plating. In addition, the study reveals that uMDSCs form myotubes when treated with MAP. CONCLUSIONS: The uMDSCs within female rat urethral striated muscle could be a therapeutic target of MAP in managing SUI.

Low-intensity extracorporeal shockwave therapy ameliorates diabetic underactive bladder in streptozotocin-induced diabetic rats.

OBJECTIVES: To evaluate the therapeutic effect of once-weekly low-intensity extracorporeal shock wave therapy (Li-ESWT) on underactive bladder (UAB) in the streptozotocin (STZ)-induced diabetic rat model. MATERIALS AND METHODS: In all, 36 female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus control (DMC), and DM with Li-ESWT (DM Li-ESWT). The two DM groups received an intraperitoneal 60 mg/kg STZ injection to induce DM. The Li-ESWT was applied toward the pelvis of the rats starting 4 weeks after STZ administration and lasting for 4 weeks. The Li-ESWT was given once weekly, with an energy flux density of 0.02 mJ/mm2 at 3 Hz for 400 pulses. All rats underwent conscious cystometry, leak-point pressure (LPP) assessment, ex vivo organ-bath study, histology, immunofluorescence, and Western Blot analysis. RESULTS: Conscious cystometry revealed voiding dysfunction in the DMC group, whereas the DM Li-ESWT group showed significantly improved voiding function, reflected in a reduced post-void residual urine volume and increased LPP compared to the DMC group. Ex vivo organ-bath studies showed that Li-ESWT enhanced muscle contractile activity of the bladder and urethra during electrical-field stimulation and drug stimulation. Histologically, Li-ESWT significantly restored bladder morphology, reflected by a reduction in the intravesical lumen area and increased muscle proportion of the bladder wall. Western Blot analysis showed higher smooth muscle actin expression in the bladder wall in the DM Li-ESWT group compared to the DMC group. Immunofluorescence showed decreased nerve-ending distribution, and destroyed and shortened nerve fibres in the DMC group, and recovery of neuronal integrity and innervation in the DM Li-ESWT group. CONCLUSIONS: In conclusion, Li-ESWT ameliorated UAB and urinary incontinence in the diabetic UAB rat model. The improvement appears to be the result of restoration of bladder and urethral structure and function by Li-ESWT. Li-ESWT is non-invasive and may become a better alternative therapy for UAB. Further investigations are warranted.

The effect of low-intensity extracorporeal shockwave therapy in an obesity-associated erectile dysfunction rat model.

OBJECTIVES: To investigate the feasibility of the Zucker fatty (ZF) rat as a model for research in to obesity-associated erectile dysfunction (OAED) and to determine the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT) on penile tissue and function in these rats. MATERIALS AND METHODS: Eight new-born male Zucker lean (ZL group) rats (ZUC-Leprfa 186) and 16 new-born male ZF rats (ZUC-Leprfa 185) were injected with 5-ethynyl-2'-deoxyuridine (EdU) at birth to identify and monitor endogenous stem cells. Insulin tolerance testing was performed at 10 weeks of age. Beginning at 12 weeks of age, eight ZF rats were kept as controls, and the remaining eight ZF rats were treated with Li-ESWT (0.02 mJ/mm2 , 3 Hz, 500 pulses; ZF + SW group) twice a week for 4 weeks. Following a 1-week washout period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Penile tissues were then harvested for histological study to assess smooth muscle/collagen content and endothelium content in the corpora cavernosum. LipidTOX™ staining was used to evaluate lipid accumulation. EdU, as a marker of cell activation, and phosphorylated histone 3 (H3P), as a marker of cell mitosis, were also assessed. RESULTS: The ICP/MAP indicated that erectile function was severely impaired in the ZF group as compared with the ZL group. In the ZF + SW group, erectile function was significantly improved (P < 0.05). Muscle atrophy was seen in the ZF group, while Li-ESWT increased the muscle content in ZF + SW group. Moreover, the penile endothelium was damaged in the ZF group, and Li-ESWT enhanced the regeneration of endothelial cells (P < 0.01) in the ZF + SW group. Lipid accumulation was seen in the penile tissue of ZF rats. Li-ESWT significantly reduced both the amount and the distribution pattern of LipidTOX, suggesting decreased overall lipid infiltration. Furthermore, Li-ESWT increased EdU-positive cells and markedly enhanced the phosphorylation level of H3P at Ser-10 in the ZF + SW group. Most H3P-positive cells were located within smooth muscle cells, with some located in the endothelium suggesting that these tissues are the reservoirs of penile stem/progenitor cells. CONCLUSION: ZF rats can serve as an animal model in which to study OAED. This study reveals that obesity impairs erectile function by causing smooth muscle atrophy, endothelial dysfunction, and lipid accumulation in the corpus cavernosum. Li-ESWT restored penile haemodynamic parameters in the ZF rats by restoring smooth muscle and endothelium content and reducing lipid accumulation. The underlying mechanism of Li-ESWT appears to be activation of stem/progenitor cells, which prompts cellular proliferation and accelerates penile tissue regeneration. Our findings are of interest, not just as a validation of this emerging treatment for erectile dysfunction, but also as a novel and potentially significant method to modulate endogenous stem/progenitor cells in other disease processes.

Low-intensity extracorporeal shock wave therapy promotes myogenesis through PERK/ATF4 pathway.

AIM: Stress urinary incontinence (SUI) is a significant health problem for women. Treatments employing muscle derived stem cells (MDSCs) may be a promising approach to this prevalent, bothersome condition, but these treatments are invasive and require collection of cells from one site for injection into another. It is also unknown whether or not these cells establish themselves and function as muscle cells in the target tissues. Alternatively, low-intensity extracorporeal shock wave therapy (Li-ESWT) is non-invasive and has shown positive outcomes in the treatment of multiple musculoskeletal disorders, but the biological effects responsible for clinical success are not yet well understood. The aim of this study is to explore the possibility of employing Li-ESWT for activation of MDSCs in situ and to further elucidate the underlying biological effects and mechanisms of action in urethral muscle. METHODS: Urethral muscle derived stem cells (uMDSCs) were harvest from Zucker Lean (ZUC-LEAN) (ZUC-Leprfa 186) rats and characterized with flow cytometry. Li-ESWT (0.02 mJ/mm2 , 3 Hz, 200 pulses) and GSK2656157, an inhibitor of PERK pathway, were applied to L6 rat myoblast cells. To assess for myotube formation, we used immunofluorescence staining and western blot analysis in uMDSCs and L6 cells. RESULTS: The results indicate that uMDSCs could form myotubes. Myotube formation was significantly increased by the Li-ESWT as was the expression of muscle heavy chain (MHC) and myogenic factor 5 (Myf5) in L6 cells in vitro. Li-ESWT activated protein kinase RNA-like ER kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α) and by increasing activating transcription factor 4 (ATF4). In addition, GSK2656157, an inhibitor of PERK, effectively inhibited the myotube formation in L6 rat myoblast cells. Furthermore, GSK2656157 also attenuated myotube formation induced by Li-ESWT. CONCLUSION: In conclusion, this experiment reveals that rat uMDSCs can be isolated successfully and can form myotubes in vitro. PERK/ATF4 pathway was involved in myotube formation, and L6 rat myoblast cells were activated by Li-ESWT to form myotubes. These findings suggest that PERK/ATF4 pathway is activated by Li-ESWT. This study elucidates one of the biochemical pathways responsible for the clinical improvements seen after Li-ESWT. It is possible that this information will help to establish Li-ESWT as an acceptable treatment modality and may help to further refine the use of Li-ESWT in the clinical practice of medicine.

In Situ Activation and Preservation of Penile Progenitor Cells Using Icariside II in an Obesity-Associated Erectile Dysfunction Rat Model.

Obesity-associated erectile dysfunction (ED) involves pathologic change that may be related to deficit of the penile endogenous stem/progenitor cells. Therefore, an in-depth study of the penile stem/progenitor cells in the pathogenesis of ED is warranted. For this study, eight Zucker Lean (ZUC-Leprfa 186; ZL group) and 16 Zucker Fatty (ZUC-Leprfa 185; ZF) male rats received an intraperitoneal injection of 5-ethynyl-2-deoxyuridine (EdU) to track endogenous stem cells. Twelve weeks later, the ZF rats were randomized to gavage feeding with 1.5 mg/kg/day of icariside II (ZF + ICA II group) or the solvent (ZF group). Treatment lasted 4 weeks and was followed by a 1-week washout period. ZF rats had impaired erectile function with related pathologic changes compared with ZL rats. ICA II treatment restored erectile function and prevented smooth muscle atrophy, endothelial dysfunction, and lipid accumulation compared with no treatment. EdU label-retaining cell levels were higher in the ZF + ICA II group compared with the ZF group. Histone 3 phosphorylation at Ser 10, a specific mitotic cell marker, was additionally used to identify dividing cells. ICA II activated more penile stem cells to proliferate in ZF rats compared with ZL rats. These results suggest that ZF rats can be used as a model for obesity-associated ED and that ICA II improves erectile function and pathologic changes through endogenous progenitor cell preservation and proliferation.

Low-Intensity Extracorporeal Shock Wave Therapy Enhances Brain-Derived Neurotrophic Factor Expression through PERK/ATF4 Signaling Pathway.

Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α), and enhanced activating transcription factor 4 (ATF4) in an energy-dependent manner. In addition, GSK2656157-an inhibitor of PERK-effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF)1α or glial cell-derived neurotrophic factor (GDNF) in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy.

Primary small cell carcinoma of kidney after renal transplantation: a case report and literature review.

Extrapulmonary small cell carcinoma (EPSCC) is a rare neoplasm comprising 2.5% to 5% of small cell carcinomas (SCCs). Bladder SCC is the most common site of genitourinary tract. Primary renal SCC is extremely rare. We report a case of primary SCC of the kidney which is rarely reported in the urinary tract and presents an aggressive clinical picture. A 59-year-old female visited a urologic clinic with complaint of persistent left flank soreness 10 years after undergoing renal transplantation. Abdominal computed tomography showed a left renal pelvis tumor. After the patient received left nephroureterectomy with bladder cuff resection, her pathology results showed SCC. After surgery, she received adjuvant systemic chemotherapy, and her recovery has been uneventful as of 8 months. Primary renal SCC presents with an advanced tumor stage and a short median survival period, therefore early intervention and close follow-up are recommended.

Renal function in patients with urinary stones of varying compositions.

Kidney stones are a potential risk factor for chronic kidney disease. The impact of different urinary stone components on renal function is unknown. In this study, we retrospectively reviewed 1,918 medical records of patients with urolithiasis. The renal function was evaluated as estimated glomerular filtration rate. All the stones were analyzed by Fourier transform infrared spectroscopy. The patients were divided into five groups according to the stone components. Statistical analysis was performed with analysis of variance. All the patients with stones had Stage 2-3 chronic kidney disease. The patients with uric acid and struvite stones had significantly lower estimated glomerular filtration rate compared with those having other stone components (p<0.01). Furthermore, the patients with calcium-containing stones (calcium oxalate and calcium phosphate) had significantly better renal function than those with non-calcium-containing stones (struvite and uric acid, p<0.01). Patients with urolithiasis had decreased renal function, and the impact of renal function varied depending on the stone components. We conclude that stone analysis is important in predicting the change in renal function in patients with urolithiasis. Moreover, the patients with non-calcium-containing stones, such as struvite and uric acid stones, should be carefully evaluated and treated to preserve their renal function.