Altered microbiota profile in seminal vesicles of men presenting with refractory hematospermia.

BACKGROUND: Currently, no recognized evidence is known about the bacterial communities found within seminal vesicles (SV) of men presenting with refractory hematospermia. METHODS AND RESULTS: Fifteen male patients with refractory hematospermia or anejaculation were enrolled, and 15 SV-Infection (SV-In) samples from SV with hemorrhage and/or stones, 11 SV-Control (SV-C) samples from SV with non-infection, and 14 Urine (Urine) samples from posterior urethra were obtained via transurethral seminal vesiculoscopy. Then the high-throughput 16 S rRNA gene sequencing method was performed to characterize the microbiota profile. Finally, a total of 1535 operational taxonomic units (OTUs) were found, 1295 OTUs were shared across three groups, 7 OTUs, 45 OTUs, and 48 OTUs were unique to SV-C group, SV-In group, and Urine group, respectively. The 5 top bacterial phyla (mean relative abundance) in all samples were Firmicutes (52.08%), Bacteroidetes (21.69%), Proteobacteria (12.72%), Actinobacteria (9.64%), and Fusobacteria (1.62%), the 5 top bacterial genera in all samples were Bacteroides (9.13%), Lactobacillus (5.38%), Bifidobacterium (5.35%), Faecalibacterium (5.10%), and Allobaculum (3.34%), of which Bifidobacterium had the highest level in SV-C samples and had a significant difference (P < 0.05) across all groups. Differential analysis showed genera Leuconostoc and LachnospiraceaeFCS020group were identified as biomarkers in the SV-In microbiota. CONCLUSION: Altered microbiota composition in seminal vesicles is related to refractory hematospermia in men, and the distribution of genus Leuconostoc or LachnospiraceaeFCS020group within seminal vesicles may interact with hematospermia. This study provides clues for the diagnosis and treatment of this urologic disorder.

Biodegradable nano black phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve injury rat model by recruiting endogenous stem/progenitor cells.

Stem cell (SC) therapy has been shown high prospects in erectile dysfunction (ED) treatment. Without ethical issues and risks of immune rejection and tumorigenesis of exogenous SC therapy, endogenous stem/progenitor cells (S/PCs) have a better potential for ED management, and their homing and redistribution are controlled by SDF1-α/CXCR4 axis. Considering black phosphorus nanosheet (BPNS) has emerged as an efficient and safe drug vehicle due to its large surface area, biodegradability, and the ability to retain and slowly release its loaded drugs, BPNS is utilized to load SDF1-α, a chemokine for S/PCs, to construct the BP@SDF1-α complex to efficiently recruit stem cells (SCs) by injury-site injection and thus ameliorate ED within the bilateral cavernous nerve injury (BCNI) rat models. We find that BP@SDF1-α can efficiently recruit exogenous SCs and endogenous S/PCs to corpus cavernosum and main pelvic ganglion (MPG) by local administration. Of note, ascribing to endogenous S/PCs recruitment, it also successfully alleviates ED in BCNI rat models by enhancing the protein expression levels of α-SMA, CD31, and nNOs, and eliciting less collagen deposition in the penis after its combined injection at corpus cavernosum and MPG. Thus, this study provides a new insight into the treatment of ED with endogenous S/PCs. BIODEGRADABLE NANO BLACK PHOSPHORUS BASED SDF1-α DELIVERY SYSTEM AMELIORATES ERECTILE DYSFUNCTION IN A CAVERNOUS NERVE INJURY RAT MODEL BY RECRUITING ENDOGENOUS STEM/PROGENITOR CELLS.

Extracellular vesicles derived from human Sertoli cells: characterizations, proteomic analysis, and miRNA profiling.

BACKGROUND: Extracellular vesicles (EVs) contain thousands of proteins and nucleic acids, playing an important role in cell-cell communications. Sertoli cells have been essential in the testis as a "nurse cell". However, EVs derived from human Sertoli cells (HSerCs) have not been well investigated. METHODS: EVs were isolated from HSerCs via ultracentrifugation and characterized by transmission electron microscopy, tunable resistive pulse sensing, and Western blotting. The cargo carried by HSerCs-EVs was measured via liquid chromatography-mass spectrometry and GeneChip miRNA Arrays. Bioinformatic analysis was performed to reveal potential functions of HSerCs-EVs. RESULTS: A total of 860 proteins with no less than 2 unique peptides and 88 microRNAs with high signal values were identified in HSerCs-EVs. Biological processes related to molecular binding, enzyme activity, and regulation of cell cycle were significantly enriched. Specifically, many proteins in HSerCs-EVs were associated with spermatogenesis and regulation of immune system, including Septins, Large proline-rich protein BAG6, Clusterin, and Galectin-1. Moreover, abundant microRNAs within HSerCs-EVs (miR-638, miR-149-3p, miR-1246, etc.) had a possible impact on male reproductive disorders such as asthenozoospermia and oligozoospermia. CONCLUSIONS: Our study has shown that HSerCs-EVs contain diverse components such as proteins and microRNAs. Further research is required to evaluate HSerCs-EVs in spermatogenesis, which are underutilized but highly potent resources with particular promise for male infertility.

Could Magnetic Resonance Imaging Help to Identify the Presence of Prostate Cancer Before Initial Biopsy? The Development of Nomogram Predicting the Outcomes of Prostate Biopsy in the Chinese Population.

PURPOSE: This study was designed to investigate the effectiveness of magnetic resonance imaging (MRI) in diagnosing prostate cancer (PCa) and high-grade prostate cancer (HGPCa) before transrectal ultrasound (TRUS)-guided biopsy. METHODS: The clinical data of 894 patients who received TRUS-guided biopsy and prior MRI test from a large Chinese center was reviewed. Based on Prostate Imaging Reporting and Data System (PI-RADS) scoring, all MRIs were re-reviewed and assigned as Grade 0-2 (PI-RADS 1-2; PI-RADS 3; PI-RADS 4-5). We constructed two models both in predicting PCa and HGPCa (Gleason score ≥ 4 + 3): Model 1 with MRI and Model 2 without MRI. Other clinical factors include age, digital rectal examination, PSA, free-PSA, volume, and TRUS. RESULTS: PCa and HGPCa were present in 434 (48.5 %) and 218 (24.4 %) patients. An MRI Grade 0, 1, and 2 were assigned in 324 (36.2 %), 193 (21.6 %) and 377 (42.2 %) patients, which was associated with the presence of PCa (p < 0.001) and HGPCa (p < 0.001). Particularly in patients aged ≤55 years, the assignment of MRI Grade 0 was correlated with extremely low rate of PCa (1/27) and no HGPCa. The c-statistic of Model 1 and Model 2 for predicting PCa was 0.875 and 0.841 (Z = 4.2302, p < 0.001), whereas for predicting HGPCa was 0.872 and 0.850 (Z = 3.265, p = 0.001). Model 1 exhibited higher sensitivity and specificity at same cutoffs, and decision-curve analysis also suggested the favorable clinical utility of Model 1. CONCLUSIONS: Prostate MRI before biopsy could predict the presence of PCa and HGPCa, especially in younger patients. The incorporation of MRI in nomograms could increase predictive accuracy.

Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in a Pelvic Neurovascular Injuries Rat Model.

INTRODUCTION: Erectile dysfunction (ED) caused by pelvic injuries is a common complication of civil and battlefield trauma with multiple neurovascular factors involved, and no effective therapeutic approach is available. AIMS: To test the effect and mechanisms of low-energy shock wave (LESW) therapy in a rat ED model induced by pelvic neurovascular injuries. METHODS: Thirty-two male Sprague-Dawley rats injected with 5-ethynyl-2'-deoxyuridine (EdU) at newborn were divided into 4 groups: sham surgery (Sham), pelvic neurovascular injury by bilateral cavernous nerve injury and internal pudendal bundle injury (PVNI), PVNI treated with LESW at low energy (Low), and PVNI treated with LESW at high energy (High). After LESW treatment, rats underwent erectile function measurement and the tissues were harvested for histologic and molecular study. To examine the effect of LESW on Schwann cells, in vitro studies were conducted. MAIN OUTCOME MEASUREMENTS: The intracavernous pressure (ICP) measurement, histological examination, and Western blot (WB) were conducted. Cell cycle, Schwann cell activation-related markers were examined in in vitro experiments. RESULTS: LESW treatment improves erectile function in a rat model of pelvic neurovascular injury by leading to angiogenesis, tissue restoration, and nerve generation with more endogenous EdU(+) progenitor cells recruited to the damaged area and activation of Schwann cells. LESW facilitates more complete re-innervation of penile tissue with regeneration of neuronal nitric oxide synthase (nNOS)-positive nerves from the MPG to the penis. In vitro experiments demonstrated that LESW has a direct effect on Schwann cell proliferation. Schwann cell activation-related markers including p-Erk1/2 and p75 were upregulated after LESW treatment. CONCLUSION: LESW-induced endogenous progenitor cell recruitment and Schwann cell activation coincides with angiogenesis, tissue, and nerve generation in a rat model of pelvic neurovascular injuries.

Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS.

Antioxidant icariside II combined with insulin restores erectile function in streptozotocin-induced type 1 diabetic rats.

Erectile dysfunction (ED) worsens in patients with diabetes mellitus (DM) despite good control of blood glucose level with insulin. Recent studies imply that diabetic vascular stresses (e.g. oxidative stress) persist in spite of glucose normalization, which is defined as metabolic memory. Studies suggest that the interaction between advanced glycation end products (AGEs) and their receptor (RAGE) mediates the development of metabolic memory. To investigate the effects of the antioxidant icariside II plus insulin on erectile function in streptozotocin (STZ)- induced type 1 diabetic rats. Fifty 8-week-old Sprague-Dawley rats were randomly distributed into five groups: normal control, diabetic, insulin-treated diabetic, icariside II-treated diabetic, and insulin plus icariside II-treated diabetic. Diabetes was induced by a single intraperitoneal injection of STZ. Eight weeks after induction of diabetes, icariside II was administered by gastric lavage once a day (5 mg/kg) for 6 weeks; and 2-6 units of intermediate-acting insulin were given to maintain normal glycemia for 6 weeks. The main outcome measures were the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP); histology of penile endothelial cells and smooth muscle cells; neural nitric oxide synthase, AGEs and RAGE expression; malondialdehyde concentration; superoxide dismutase activity; and apoptosis index. Diabetic rats demonstrated a significantly lower ICP/MAP ratio, reduced penile endothelial cells, reduced smooth muscle cells, increased AGEs and RAGE, and increased apoptosis. Insulin and icariside II monotherapy partially restored erectile function and histological changes. However, the combination therapy group showed significantly better erectile parameters, cytological components and biochemistry, similar to those in the normal control group. These results suggest that, although insulin can effectively control glycemic levels, it does not completely alter the pathological changes in erectile tissues. Better efficacy could be expected with tight glycemic control plus the antioxidant icariside II. The proposed combination therapy might have the potential to eliminate metabolic memory by down-regulating the AGEs-RAGE-oxidative stress axis.

Studies on the mechanism of testicular dysfunction in the early stage of a streptozotocin induced diabetic rat model.

Streptozotocin (STZ) induced diabetic model has been widely used to study the effects of diabetes mellitus (DM) on male infertility, but it remains unclear whether the responses in this model are due to hyperglycemia or STZ per se. This study was designed to investigate the mechanism of STZ on testicular dysfunction. In the present study, sperm characteristics, serum testosterone, steroidogenic enzymes (StAR and 3ß-HSD), and the vimentin apical extension of sertoli cells decreased significantly in the STZ group compared with those in the normal controls (p<0.05), while Johnsen's score, testicular lipid peroxidation, spermatogenic cell apoptosis, and the expressions of NF-κB and Wnt4 significantly increased (p<0.05). Insulin replacement mainly restored the decreased serum testosterone and steroidogenic enzymes, but not other parameters. The results indicated that spermatogenic dysfunction in the early stage of STZ-induced diabetic rats was due to direct STZ cytotoxicity to sertoli cells, which could be regulated by Wnt4 and NF-κB, while steroidogenic dysfunction might be a direct or indirect consequence of insulin deficiency. The results suggested that STZ-induced diabetic model, at least in the early stage, is not suitable to study the diabetes-related spermatogenic dysfunction.

Clinical investigation of a novel surgical device for circumcision.

PURPOSE: We investigated the performance of a novel device for adult circumcision, that is the circular cutter with stapled anastomosis for circumcision. MATERIALS AND METHODS: A total of 62 men with a mean ± SD age of 28 ± 8 years were enrolled from June to September 2012 to undergo circumcision using the circular cutter with stapled anastomosis. The device used 18 staples for anastomosis, which fall out during the recovery course, as designed. Patients were followed at day 3, and weeks 1, 2, 4 and 12 after the procedure. Outcome measures were evaluated, including patient safety, procedural time, patient satisfaction and complication rate. RESULTS: Average procedural time needed to use the device was 7.7 ± 2.6 minutes. Patients returned to full physical activity on postoperative day 3. The overall complication rate was 4.8%, including 1 case of intraoperative bleeding due to operator inexperience and 2 of a delay in staples falling out. No patient experienced wound infection or excessive foreskin excision. No incision site edema was observed beyond postoperative day 7. All enrolled patients were satisfied with the postoperative penile cosmesis. CONCLUSIONS: The circular cutter with stapled anastomosis for circumcision is a 1-step device that can achieve excellent postoperative results with minimal procedural time. Therefore, it has the potential to enable the performance of circumcision as a rapid turnover bedside procedure.

The self-estimation index of erectile function-no sexual intercourse (SIEF-NS): a multidimensional scale to assess erectile dysfunction in the absence of sexual intercourse.

INTRODUCTION: A new concept of Erectile Dysfunction with No Sexual Intercourse (ED-NS) is proposed to acknowledge the subpopulation of patients who are unable to achieve or sustain an erection in the absence of sexual intercourse. Since the commonly used ED diagnostic tool, International Index of Erectile Function Questionnaire is not able to adequately assess the erectile function (EF) in the absence of intercourse, the researchers developed a new 10-item questionnaire to better evaluate the EF in this special patient subpopulation: Self-Estimation Index of Erectile Function-No Sexual Intercourse (SIEF-NS). AIM: To validate the reliability, sensitivity and specificity of SIEF-NS. METHODS: The study was carried out in three phases. Phase one applied component analysis to 126 ED-NS patients to search for the primary factors and Cronbach's alpha standardized statistic values for SIEF-NS. Phase two applied discriminant analysis to participants' (212 ED-NS patients and 193 normal controls) scores on each question item, each factor and the overall 10-item questionnaire. Phase three investigated SIEF-NS's capability of evaluating treatment effect on 41 ED-NS patients. MAIN OUTCOME MEASURES: Reliability, sensitivity and specificity were defined and used to evaluate the performance of SIEF-NS. RESULTS: EF by autonomic response (factor 1) and EF with potential sexual partners (factor 2) are the two primary factors with eigenvalues greater than 1.0. High degree of internal consistency was observed for the two factors and the 10-item questionnaire (Cronbach's alpha values: 0.871 for 10 items, 0.84 for factor 1, and 0.823 for factor 2). SIEF-NS demonstrated adequate construct validity, high sensitivity (0.925) and specificity (0.829) to diagnose ED-NS. The EF scores of ED-NS patients post treatment showed significant improvement (P < 0.05). CONCLUSION: SIEF-NS can be used to identify ED-NS patients and detect treatment-related EF changes in ED-NS patients.

Therapeutic potential of adipose-derived stem cells-based micro-tissues in a rat model of postprostatectomy erectile dysfunction.

INTRODUCTION: Stem cells (SCs) show significant benefits in the treatment of postprostatectomy erectile dysfunction (ED). However, the low retention rate of the traditional single-cell strategy at the injection sites limits its therapeutic potential. AIM: This study aims to investigate the feasibility and mechanism of adipose-derived stem cells (ADSCs)-based micro-tissues (MTs) in the treatment of ED in a rat model of bilateral cavernous nerves (CNs) injury. METHODS: ADSCs labeled with 5-ethynyl-2-deoxyuridine (EdU) were used to generate MTs with hanging drop method. 10 Sprague-Dawley (SD) rats underwent sham surgery and intracavernous (IC) injection of phosphate buffer solution (PBS) (the sham group). Another 70 rats underwent bilateral CN crush and were then treated with PBS (n = 10, the crush group), dissociated ADSCs (n = 30, the ADSCs group), and MTs (n = 30, the MTs group), respectively. At day 1, 3, 7, 14 (n = 5), and 28 (n = 10) postsurgery, specimens were harvested for histology. At day 28, 10 rats in each group were examined for erectile function before tissue harvest. MAIN OUTCOME MEASURES: Light microscopy of the dynamic aggregation of the MT, immunohistologic examination of the MTs, the retention and distribution of EdU + ADSCs in the corpus cavernosum (CC), and the penis histological analyses of collagen content, Western blot of functional proteins in MTs, intracavernous pressure recording on CN electrostimulation. RESULTS: Three-day-old MTs became stable and expressed nerve growth factor, vascular endothelial growth factor, C-X-C chemokine receptor type 4, Wnt5a, and collagen IV. More EdU + ADSCs retained in the CC in the MTs group than that in the ADSCs group. IC injection of MTs resulted in significant restoration of the erectile function and histopathological changes compared with the ADSCs group. CONCLUSION: IC-injected MTs resulted in a better restoration of erectile function than traditional single-cell strategy. The underlying mechanisms of recovery appear to involve enhanced cellular retention in the penis and upregulation of some paracrine factors.

AGE-breaker ALT-711 plus insulin could restore erectile function in streptozocin-induced type 1 diabetic rats.

INTRODUCTION: The interaction between advanced glycation end-products (AGEs) and its receptors for AGEs (RAGEs) elicits oxidative stress and mediates the development of erectile dysfunction (ED). ALT-711, an AGE cross-link breaker, has the therapeutic potential for ED but has been less intensively investigated. AIM: The aim of this study was to investigate the effects of an AGEs breaker 3-phenacyl-4,5-dimethylthiazolium chloride (ALT-711) plus insulin on erectile function in streptozocin (STZ)-induced type 1 diabetic rats. METHODS: Fifty 8-week-old Sprague-Dawley rats were randomly distributed into five groups: normal control (C), diabetic (D), insulin-treated diabetic (D + I), ALT-711-treated diabetic (D + ALT-711) and insulin plus ALT-711-treated diabetic (D + I + ALT-711) rats. Diabetes was induced by a single intraperitoneal injection of STZ. Eight weeks after induction of diabetes, ALT-711 was administered by intraperitoneal injection. Two to six units of intermediate-acting insulin were utilized to achieve normal levels of glycemic control. After treatment for 6 weeks, erectile function was determined via measurement of intracavernous pressures (ICPs) following electrostimulation of the cavernous nerve. The deposition of AGEs, expression of RAGEs, superoxide dismutase activity, and lipid peroxidation were measured. We also evaluated penile histological changes such as smooth muscle contents, endothelial cells contents, and apoptotic activity. MAIN OUTCOME MEASURES: The main outcome measures were the ratio of ICP/mean arterial pressure (MAP), penile endothelial cells, smooth muscle cells, neuronal nitric oxide synthase, AGE and RAGE expression, malondialdehyde concentration, SOD activity, and apoptosis index. RESULTS: Diabetic rats demonstrated significantly reduced ICP/MAP ratio, penile endothelial cells, smooth muscles cells, increased AGEs and RAGE expression, and increased apoptosis. Insulin and ALT-711 monotherapy partially restored erectile function and histological changes. However, the combination therapy group showed erectile parameters and components similar to those in C. ALT-711-treated group demonstrated less deposition of AGEs and lower expression of RAGE than those in insulin-treated group. CONCLUSION: These results suggest that although insulin can effectively control glycemic levels, it does not completely alter the pathological changes in erectile tissues. Better efficacy could be expected with tight glycemic control plus ALT-711, an AGEs cross-link breaker. The combination therapy might have the potential to eliminate metabolic memory by down-regulating the AGEs-RAGE oxidative stress axis.

A novel protein is lower expressed in renal cell carcinoma.

Engrailed-2 (EN2) has been identified as a candidate oncogene in breast cancer and prostate cancer. It is usually recognized as a mainly nuclear staining in the cells. However, recent studies showed a cytoplasmic staining occurred in prostate cancer, bladder cancer and clear cell renal cell carcinoma. The inconsistency makes us confused. To clarify the localization and expression of EN2 in renal cell carcinoma, anti-EN2 antibody (ab28731) and anti-EN2 antibody (MAB2600) were used for immunohistochemistry (IHC) respectively. Interestingly, we found that EN2 detected by ab28731 was mainly presented in cytoplasm while EN2 detected by MAB2600 was mainly presented in nucleus. To further investigate the different patterns observed above, lysates from full-length EN2 over expression in HEK293T cells were used to identify which antibody the EN2 molecule bound by western blot. Results showed ab28731 did not react with the lysates. For this reason, the novel specific protein detected by ab28731 was not the EN2 molecule and was named nonEN2. Then using the renal carcinoma tissue microarray and renal tissues, we found that the protein expression levels of nonEN2 in kidney tumor tissues was significantly lower than that in kidney normal tissues (p < 0.05), so was in renal cell lines. Taken together, nonEN2 is lower expressed and may play an important role in renal cell carcinoma.

Prophylactic protective effects and its potential mechanisms of IcarisideII on streptozotocin induced spermatogenic dysfunction.

The aim of this study was to investigate the effects of IcarisideII(ICAII) on the prevention of streptozotocin (STZ) induced spermatogenic dysfunction. Forty male Sprague-Dawley rats received intraperitoneal injection of STZ (55 mg/kg) and were equally randomized to gavage feeding of vehicle (the vehicle group) or ICAII (0.5, 1.5 or 4.5 mg/kg/day, respectively). Ten normal rats received vehicle and served as control. Four weeks later, sperm parameters, histopathological changes, testicular lipid peroxidation, antioxidant enzyme activities, and apoptosis index (AI) were evaluated. Results showed that ICAII treatment resulted in a significant recovery of sperm parameters and histopathological changes relative to the vehicle group (p<0.05). In the vehicle group, antioxidant enzyme activities and the expression of Sertoli cell Vimentin filaments obviously decreased, while lipid peroxidation and AI significantly increased as compared with the control group (p<0.05). Following ICAII treatment, corrective effects on these items towards normal levels were observed. The results suggested that ICAII has beneficial effect on the preservation of spermatogenic function in the STZ-induced diabetic rats. The mechanisms might be related to its improvement of antioxidant enzyme activities, preservation of the protein expression and apical extensions of Vimentin filaments, and anti-apoptosis capability.

Effects of Icariside II on corpus cavernosum and major pelvic ganglion neuropathy in streptozotocin-induced diabetic rats.

Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II) on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily). Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining) and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro) was greatly attenuated in the ICA II-treated group (p < 0.01). ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes.

Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model.

Introduction. Low-energy shockwave therapy (LESWT) has been shown to improve erectile function in patients suffering from diabetes mellitus (DM)-associated erectile dysfunction (ED). However, the underlying mechanism remains unknown. Aim. The aim of this study is to investigate whether LESWT can ameliorate DM-associated ED in a rat model and examine the associated changes in the erectile tissues. Methods. Newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine (EdU; 50 mg/kg) for the purpose of tracking endogenous mesenchymal stem cells (MSCs). Eight weeks later, eight of these rats were randomly chosen to serve as normal control (N group). The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce DM. Eight of these rats were randomly chosen to serve as DM control (DM group), whereas another eight rats were subject to shockwave (SW) treatment (DM+SW group). Each rat in the DM+SW group received 300 shocks at energy level of 0.1 mJ/mm(2) and frequency of 120/minute. This procedure was repeated three times a week for 2 weeks. Another 2 weeks later, all 24 rats were evaluated for erectile function by intracavernous pressure (ICP) measurement. Afterward, their penile tissues were examined by histology. Main Outcome Measures. Erectile function was measured by ICP. Neuronal nitric oxide synthase (nNOS)-positive nerves and the endothelium were examined by immunofluorescence staining. Smooth muscle and MSCs were examined by phalloidin and EdU staining, respectively. Results. STZ treatment caused a significant decrease in erectile function and in the number of nNOS-positive nerves and in endothelial and smooth muscle contents. These DM-associated deficits were all partially but significantly reversed by LESWT. MSCs (EdU-positive cells) were significantly more numerous in DM+SW than in DM rats. Conclusion. LESWT can partially ameliorate DM-associated ED by promoting regeneration of nNOS-positive nerves, endothelium, and smooth muscle in the penis. These beneficial effects appear to be mediated by recruitment of endogenous MSCs. Qiu X, Lin G, Xin Z, Ferretti L, Zhang H, Lue TF, and Lin C-S. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med 2013;10:738-746.

Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats.

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment.

[Progress of low-energy shockwave therapy in clinical application].

A shock wave is a transient pressure disturbance that propagates rapidly in three-dimensional space. It is associated with a sudden rise from ambient pressure to its maximum pressure. Shock wave therapy in urology is primarily used to disintegrate urolithiasis. Recently, low-energy shock wave therapy (LESWT), which is a novel convenient and cost-effective therapeutic modality, is extended to treat other pathological conditions including coronary heart disease, musculoskeletal disorders and erectile dysfunction. However, the exact therapeutic mechanisms and clinical safety and efficacy of LESWT remain to be investigated. Based on the results of previous studies, it is suggested that LESWT could regulate angiogenesis-related growth factors expression including endothelial nitric oxide synthase (eNOS), vessel endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA), which might induce the ingrowth of neovascularization that improves blood supply and increases cell proliferation and eventual tissue regeneration for restore pathological changes. The further studies on cellular and molecular biological changes by LESWT for clarification its mechanism and clinical safety and efficacy studies are recommended.

[Efficacy of microsurgical vasectomy reversal on patients after vasectomy].

OBJECTIVE: To evaluate the efficacy of microsurgical vasectomy reversal on patients after vasectomy. METHODS: In the study, 41 patients after vasectomy were admitted for microsurgical vasectomy reversal. The mean (range) age was 45 (29 to 66) years for the men. The mean duration of obstruction was 12 years. All the patients were seen by the surgeon for a complete history and physical examination. Semen analyses proved azoopermia, and their serum levels of sexual hormone were normal. They were all offered scrotal exploration. Microvasovasostomy was performed if the sperm was found in the material coming from the proximal vas lumen. The decision for microvasoepididymostomy was made during surgery, if the fluid was creamy, containing only debris or there was no fluid whatsoever when the vas was milked toward the cut end. Microvasovasostomy was performed in 40 patients, of whom 6 were with lateral microvasoepididymostomy and 1 with bilateral microvasoepididymostomy. The initial semen analysis was then done after usually 3 months postoperatively. Patency was arbitrarily defined as>10 000 sperm/mL in ejaculate in at least one semen analysis after surgery. Postoperative patency rate and postoperative impregnation rate were followed. RESULTS: The 41 patients were followed up for 3 to 72 months, and 5 cases were lost. In the 28 patients who had obstructions for less than 15 years, 3 were lost. Sperm was found by semen analysis in 21 patients. Their sperm density was 2×10(6) to 46×10(6) sperms/mL and motility was 0% to 60%. The semen analysis revealed azoospermia in 2 patients after 12 months, who were advised to undergo intracytoplasmic sperm injection. Natural conception occurred in 6 patients followed for more than 12 months. The overall patency rate was 84% (21/25). Among the patients with a follow-up of >6 months, the natural paternity rate was 29% (6/21). In the 13 patients who had obstructions for more than 15 years, 2 were lost. The patency and pregnancy rates were 64% (7/11) and 14% (1/7) respectively. Their sperm density was 0.02×10(6) to 30× 10(6) sperms/mL and motility was 0% to 43%. CONCLUSION: Microsurgical vasectomy reversal is an effective method to treat vasal obstruction due to vasectomy. The patency and pregnancy rates are related to the time of vasectomy. The patency and pregnancy rates are higher in patients with obstruction for less than 15 years than those for more than 15 years.

[Transperineal ultrasonic therapy for chronic prostatitis].

OBJECTIVE: To evaluate the clinical efficacy and safety of transperineal ultrasonic therapy for chronic prostatitis (CP) by analyzing the scores of NIH-CPSI and the results of prostate fluid routine examination. METHODS: We conducted a randomized, double-blind, multi-centered trial on 96 CP patients that met the inclusion criteria. We divided the patients into groups A (trial) and B (control) of equal number, the former treated by transperineal ultrasound, while the latter with the same machine but no ultrasound waves, 10 min a time qd alt for 2 weeks. Then we evaluated the therapeutic effect and safety by comparing the scores of NIH-CP-SI and counts of white blood cells (WBC) and lecithin corpuscles (LC) in the prostate fluid between the two groups before and after treatment. RESULTS: The total effectiveness rate was 70.83% in group A and 25% in group B (P < 0.01). The scores on prostate pain, urinary symptoms and quality of life as well as the total NIH-CPSI score were significantly improved in group A as compared with pretreatment (P < 0.05), and so were the prostate pain score and total NIH-CPSI score in group B (P < 0.05). Statistically significant differences were observed between the two groups in the scores on prostate pain and urinary symptoms and total NIH-CPSI score after treatment (P < 0.05), but not in any of the NIH-CPSI scores before treatment (P > 0.05), nor were there any significant differences in the counts of WBCs and LC either between the two groups or within each group before and after treatment (P > 0.05). Two patients experienced adverse events in group A, and 1 in group B (P > 0.05). CONCLUSION: Transperineal ultrasonic therapy is highly effective for CP, especially in relieving prostate pain. With its advantages of safety, easy operation and high acceptability, it deserves a wider clinical application.