Genetically predicted insomnia causally increases the risk of erectile dysfunction.

Sleep has attracted extensive attention due to its significance in health. However, its association with erectile dysfunction (ED) is insufficiently investigated. To investigate the potential causal links between sleep traits (insomnia, sleep duration, and chronotype) and ED, this study was performed. The single-nucleotide polymorphisms (SNPs) associated with insomnia, sleep duration, and chronotype were retrieved from previous genome-wide association studies (GWAS). A conventional two-sample Mendelian randomization (MR) was used to estimate the causal links between sleep traits and ED. The summary statistics of ED were from individuals of European ancestry (6175 cases vs 217 630 controls). As shown by the random effect inverse-variance-weighting (IVW) estimator, genetically predicted insomnia was causally associated with a 1.15-fold risk of ED (95% confidence interval: 1.07-1.23, P < 0.001). Sleep duration and morningness were not causally associated with ED, as indicated by the IVW (all P > 0.05). These findings were consistent with the results of sensitivity analyses. Based on genetic data, this study provides causal evidence that genetically predicted insomnia increases the risk of ED, whereas sleep duration and chronotype do not.

The association between heavy metal exposure and erectile dysfunction in the United States.

Literature regarding the impacts of heavy metal exposure on erectile dysfunction (ED) is scarce. We aimed to evaluate the correlation between 10 urinary metals and ED in a large, nationally representative adult male sample. The dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2001-2002 and 2003-2004. Weighted proportions and multivariable logistic regression analysis adjusted for confounding variables were utilized to determine the relationship between metal exposure and ED. Weighted quantile sum (WQS) regression was utilized to evaluate the impact of a mixture of urinary metals on ED. A total of 1328 participants were included in our study. In multivariable logistic regression analysis, cobalt (Co) and antimony (Sb) were positively associated with ED (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.73, P = 0.020; and OR: 1.41, 95% CI: 1.12-1.77, P = 0.018, respectively) after full adjustment. Men in tertile 4 for Co (OR: 1.49, 95% CI: 1.02-2.41, P for trend = 0.012) and Sb (OR: 1.53, 95% CI: 1.08-2.40, P for trend = 0.041) had significantly higher odds of ED than those in tertile 1. Furthermore, the WQS index was significantly linked with increased odds of ED after full adjustment (OR: 1.31, 95% CI: 1.04-1.72, P < 0.05). Our study expanded on previous literature indicating the possible role of heavy metal exposure in the etiology of ED. The evaluation of heavy metal exposure should be included in the risk assessment of ED.

Depressive males have higher odds of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a retrospective cohort study based on propensity score matching.

Lower urinary tract symptoms suggestive of benign prostate hyperplasia (LUTS/BPH) and depression are both increasing in Chinese aging males. However, the relationship still remains unknown. To explore their relationship, a retrospective cohort study based on propensity score matching (PSM) was conducted by analyzing the China Health and Retirement Longitudinal Study dataset. After data cleaning, a total of 5125 participants were enrolled and subjected to PSM; 1351 pairs were matched and followed for 2 years. Further logistic regression and restricted cubic spline (RCS) were performed to evaluate, model and visualize the relationship between depression and LUTS/BPH. Moreover, subgroup analyses and sensitivity analyses were adopted to verify the robustness of the conclusions. Before PSM, depressive patients showed higher odds of LUTS/BPH in all three models adjusting for different covariates (P < 0.001). After PSM, univariate logistic regression revealed that depressive patients had higher risks for LUTS/BPH than participants in the control group (odds ratio [OR] = 2.10, P < 0.001). The RCS results indicated a nonlinear (P < 0.05) and inverted U-shaped relationship between depression and LUTS/BPH. In the subgroup analyses, no increased risks were found among participants who were not married or cohabitating, received an education, had an abnormal body mass index (<18.5 kg m-2 and ≥28 kg m-2), slept more than 6 h, did not smoke, and drank less than once a month (all P > 0.05). The results of sensitivity analyses indicated identical increased risks of LUTS/BPH in all four models (all P < 0.001). In conclusion, depression enhances the risks of LUTS/BPH in aging males.

Vacuum therapy ameliorates erectile dysfunction in bilateral cavernous nerve crush rats by inhibiting apoptosis and activating autophagy.

Postprostatectomy erectile dysfunction (pPED) remains a current problem despite improvements in surgical techniques. Vacuum therapy is clinically confirmed as a type of pPED rehabilitation. However, its underlying mechanisms are incompletely understood. Recently, autophagy and apoptosis were extensively studied in erectile dysfunction resulting from diabetes, senescence, and androgen deprivation but not in the context of pPED and vacuum therapy. Therefore, this study was designed to investigate the roles of autophagy and apoptosis in pPED and vacuum therapy. Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: the control group, bilateral cavernous nerve crush (BCNC) group, and BCNC + vacuum group. After 4 weeks of treatment, intracavernosal pressure was used to evaluate erectile function. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to measure the molecular expression. TdT-mediated dUTP nick-end labeling staining was used to assess apoptosis. Transmission electron microscopy was used to observe autophagosomes. After treatment, compared with those of the BCNC group, erectile function and cavernosal hypoxia had statistically significantly improved (P < 0.05). Apoptosis and the relative protein expression of B-cell lymphoma-2-associated X and cleaved Caspase3 were decreased (P < 0.05). Autophagy-related molecules such as phosphorylated unc-51-like autophagy-activating kinase 1 (Ser757) and p62 were decreased. Beclin1, microtubule-associated protein 1 light chain 3 A/B, and autophagosomes were increased (P < 0.05). Besides, the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway, as a negative regulator of autophagy to some degree, was inhibited. This study revealed that vacuum therapy ameliorated pPED in BCNC rats by inhibiting apoptosis and activating autophagy.

N-acetylcysteine maintains penile length and erectile function in bilateral cavernous nerve crush rat model by reducing penile fibrosis.

Penile length shortening and erectile dysfunction are common complications after radical prostatectomy. Various methods have been used to maintain erectile function, but less attention has been paid to preserving penis length. N-acetylcysteine (NAC) has the effect of antioxidation and antifibrotic, which may be beneficial to improve those postoperative complications. This study investigated the effect of NAC on maintaining the penile length and the erectile function after bilateral cavernous nerve crush (BCNC) and its underlying mechanism. Twenty-four male rats were randomly divided into three groups: control group, BCNC group, and BCNC + NAC group. NAC or equal volume of saline was daily administrated by intragastric gavage for 4 weeks. The initial and end penile lengths were measured. Intracavernosal pressure/mean arterial pressure (ICP/MAP) ratio was calculated to assess erectile function. Hematoxylin-eosin staining, Masson's trichrome staining, immunohistochemistry, and Western blot were performed to explore cellular and molecular changes of the penis. Compared to the BCNC group, the penile length, ICP/MAP ratio and smooth muscle/collagen ratio in the BCNC + NAC group were improved significantly (all P < 0.05), and the expressions of endothelial nitric oxide synthase, α-smooth muscle actin, glutathione, and glutathione peroxidase 1 were significantly increased after NAC treated (all P < 0.05), along with the decreased expressions of hypoxia-inducible factor-1α, transforming growth factor-ß1, collagen I, collagen III, collagen IV, malonaldehyde, and lysine oxidase (all P < 0.05). This study demonstrated that NAC could maintain penile length and partly improve erectile function. Possible mechanism is directly and/or indirectly related to antihypoxic and antifibrosis.

Vacuum therapy prevents corporeal veno-occlusive dysfunction and penile shrinkage in a cavernosal nerve injured rat model.

Erectile dysfunction and penile shrinkage are the common complications after radical prostatectomy. Penile rehabilitation is widely applied after the surgery. Vacuum therapy is one of the three penile rehabilitation methods used in the clinical setting, but its mechanism is not well known. This study was designed to investigate whether vacuum erectile device (VED) can prevent corporeal veno-occlusive dysfunction and penile shrinkage in the bilateral cavernous nerve crush (BCNC) rat model. Adult male Sprague-Dawley rats were randomly assigned into three groups: sham group, BCNC group, and BCNC + VED group. After 4 weeks, penile length and intracavernosal pressure (ICP) were measured, and then the middle part of the penis was harvested after dynamic infusion cavernosometry to complete the following items: smooth muscle/collagen ratios and collagen I/III ratios; ultramicrostructure of the tunica albuginea, endothelial cell, and smooth muscle cell; and the expression of calponin-1 and osteopontin. The penile shortening, peak ICP and ICP drop rate after alprostadil injection were significantly improved with vacuum therapy after 4-week treatment. Compared with BCNC group, VED significantly increased smooth muscle/collagen ratios, decreased collagen I/III ratios, and preserved the ultramicrostructure of the tunica albuginea, endothelial cell, and smooth muscle cell. The data also showed that animals exposed to VED could partially reverse the expression of calponin-1 and osteopontin induced by BCNC. In conclusion, vacuum therapy is effective to prevent penile shrinkage and veno-occlusive dysfunction in penile rehabilitation, which may be associated with well-preserved structure and function of the tunica albuginea, endothelial cell, and smooth muscle cell.

Anti-lysyl oxidase combined with a vacuum device induces penile lengthening by remodeling the tunica albuginea.

This study aimed to explore whether and how anti-lysyl oxidase (anti-LOX) combined with a vacuum device (VD) could promote penile lengthening and to evaluate the effect on erectile function. This study was performed on four groups of adult rats: control, anti-LOX, VD (negative pressure value of -300 mmHg), and anti-LOX + VD. Penile length was measured by a modified VD method and verified on exposed length data. Intracavernous pressure (ICP) and maximum ICP/mean arterial pressure (MAP) ratio were recorded to assess erectile function. For corpus cavernosum, LOX activity and concentrations of pyridinoline, desmosine, hydroxyproline, and elastin were analyzed; transmission electron microscope and Hart's elastin staining were performed to monitor microstructural changes. Anti-LOX and VD significantly lengthened the penis by 10.8% (3.75 mm) and 8.2% (2.48 mm) compared with the control group, respectively, while anti-LOX + VD achieved the longest penile size (40.58 ± 0.40 mm) which was 17.4% longer than the control group (34.58 ± 0.54 mm). After 1-week washout, no penile retraction was observed. Meanwhile, exposed penile length data confirmed that the penis in the anti-LOX + VD group was also significantly longer. Anti-LOX inhibited LOX activity to reduce pyridinoline level, which led the penile tunica albuginea remodeling. However, it had no effect on hydroxyproline, desmosine, and elastin levels. Moreover, anti-LOX had no impact on erectile function, which was determined by ICP and ICP/MAP ratio. These results suggest that anti-LOX elongates the penis by reducing pyridinoline, which induces tunica albuginea remodeling. This lengthening effect was more obvious when combined with a VD. All procedures had no impact on erectile function.

Optimal pressure in penile rehabilitation with a vacuum erection device: evidence based on a rat model.

Vacuum erection device (VED), used to treat radical prostatectomy (RP)-associated erectile dysfunction, has attracted considerable attention. However, the optimal negative pressure remains to be determined. This investigation explored the optimal pressure for VED therapy in penile rehabilitation. Thirty-six 9-week-old male rats were randomly divided into six groups: control groups (sham group, bilateral cavernous nerve crush [BCNC] group) and VED therapy groups (-200 mmHg group, -300 mmHg group, -400 mmHg group, -500 mmHg group). BCNC group and VED therapy groups underwent BCNC surgery. Intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was calculated to assess erectile function. Masson's trichrome (MT) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry, and real-time polymerase chain reaction (RT-PCR) were performed to explore cellular and molecular changes of the penis. Compared to the BCNC group, ICP/MAP ratios in all VED treatment groups were improved significantly (all P < 0.05), but there were no statistically significant differences among VED therapy groups. With increased pressure, complications gradually emerged and increased in frequency. Expression of molecular indicators, such as endothelial nitric oxide synthase (eNOS) and alpha-smooth muscle actin (α-SMA), increased after VED therapy, and hypoxia-inducible factor 1α (HIF-1α) and transforming growth factor beta (TGF-ß) decreased. In addition, VED therapy improved the outcomes of MT and TUNEL assay. This investigation demonstrated a pressure of -200 mmHg in a rat model is optimal for VED therapy for penile rehabilitation after RP. No further benefits were observed with increased pressure, despite an increase in complications.

[Animal models of Peyronie's disease: An update].

Peyronie's disease is characterized by local fibrosis of the tunica albuginea and relatively rare clinically. Few relevant basic researches could be retrieved, which might be attributed to the absence of a robust animal model of the disease as well as to its rareness. At present, some animal models available for Peyronie's disease have their own merits and demerits. TGF-ß1-induced and Fibrin-induced models are lack of penile curvature and calcification/ossification. A surgical model might be established for the acute phase of the disease. The characteristic of a widespread fibrotic process involving many organs in the spontaneous model is quite different from that of human Peyronie's disease. Therefore, choosing the right model is essential for researches. This paper presents an overview of the animal models of Peyronie's disease, meant to provide some reference for the basic research of the disease.

[No-flip method versus external method for Shang Ring circumcision: a meta-analysis].

OBJECTIVE: To compare the effect and safety of the no-flip method versus the external method in Shang Ring circumcision. METHODS: We searched relevant randomized controlled trials published in China and abroad comparing the no-flip method and external method of Shang Ring circumcision. Based on the Cochrane Handbook for systematic review, two reviewers independently eval- uated the quality of the included studies and abstracted relevant data, followed by a meta-analysis using the statistical software Review Manager 5.1.0. RESULTS: Totally 7 studies with 1 200 cases were included. Compared with the external method, the no-flip method was associated with a lower total rate of complications (RR = 0.40, 95% CI: 0.18, 0.87, P = 0.02), a lower incidence of postop- erative edema (RR = 0.28, 95% CI: 0.09, 0.81, P = 0.02), and a lower 24 h postoperative pain score (MD = -0.35, 95% CI: -0.55, -0.14, P < 0.001). CONCLUSION: The no-flip method of Shang Ring circumcision was superior to the external method for its advantages of fewer complications, lower incidence of postoperative edema, and mild postoperative pain. However, our findings need further support by more high-quality randomized controlled trials.

[Strategies for the treatment and prevention of priapism in children].

Priapism is defined as abnormal persisting penile erection beyond or unrelated to sexual stimulation. It is rare in children and the appropriate management consensus is lacking. We have reviewed the literature on the treatment and prevention of priapism in children in the last 5 years. The following advances were reported: (1) compression or thrombin injection guided by ultrasound in nonischemic priapism prior to selective angioembolization; (2) anti-androgen therapy is the key for the prevention of nonischemic priapism occurring and reoccurring after angioembolization; (3) etiological interventions are enough to resolve some priapism in children; (4) T tunnel may be applied to the distal shunt failed cases in children. Combined with the new progress in treatment of priapism in children, we have designed the algorithm of priapism management and the algorithm of stuttering priapism prevention. The two algorithms will be helpful for clinicians dealing with the clinical challenges in children's priapism management.

[Advances in superenzyme gene therapy in penile rehabilitation].

Erectile dysfunction (ED) is an almost unavoidable complication of radical prostatectomy. At present, though the concept of penile rehabilitation (PR) is accepted by most clinicians, the outcomes of erectile function recovery vary widely. Prostacyclin (PGI2) is a prostanoid and a main vasoprotectant which induces smooth muscle relaxation, but not used for replacement therapy because of its high unstability. SuperEnzyme is capable of continuous, specific and targeted promotion of PGI2 synthesis, and helps PR in ED patients after radical prostatectomy. SuperEnzyme gene therapy has a promising prospect for PR and the management of ED. This review updates SuperEnzyme gene therapy in PR.

Chaihu-Shugan-San, an oriental herbal preparation, for the treatment of chronic gastritis: a meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic gastritis is a very common disease of the digestive tract. Although herbal preparation Chaihu-Shugan-San (CSS) has been widely used as an alternative treatment for chronic gastritis in East Asia, its effectiveness is not verified. The purpose of this meta-analysis is to evaluate the effectiveness of CSS in treating various types of chronic gastritis. MATERIALS AND METHODS: Retrospective review of pertinent literature via Embase, China National Knowledge Infrastructure database, Wanfang Data, Vip Information and the Cochrane Library search using the keywords "Chaihushugan" or "Chaihu Shugan" or "Chai Hu Shu Gan" or "Chaihu Shu Gan". Twenty-one trials were identified including 2572 patients (1384 in CSS group and 1188 in chemotherapy group). Each trial was independently reviewed by two assessors. RESULTS: The risk ratios of bile reflux gastritis, chronic superficial gastritis, chronic atrophic gastritis, and chronic erosive gastritis in the CSS-treated and chemotherapy groups were 1.30, 1.20, 1.24, and 1.48, respectively. CSS had more therapeutic effect in various types of chronic gastritis patients for improving clinical response compared with the chemotherapy group. Of the 21 trials administrating CSS to patients, no adverse event was reported. CONCLUSIONS: CSS was more effective compared to chemotherapy in the treatment of chronic gastritis and no serious side-effects were identified. However, the evidence is insufficient because of the low methodological quality of the included trials. More full-scale, randomized, double-blind, placebo-controlled clinical trials are recommended to further evaluate the therapeutic benefit of CSS.

Meta-analysis of randomized controlled trials to assess the effectiveness and safety of Free and Easy Wanderer Plus, a polyherbal preparation for depressive disorders.

Free and Easy Wanderer Plus (FEWP) is a polyherbal preparation which therapeutic benefits have been extensively evaluated in patients with various depressive disorders. The purpose of this meta-analysis was to assess the overall effectiveness and safety of FEWP. Following systematic review, a total of 14 high-quality randomized controlled trials (RCTs) were identified and included in the meta-analysis. Statistically greater treatment effects were found in FEWP monotherapy compared to placebo and in FEWP combined with conventional anti-depressants (CADs) compared to CADs alone. Patients taking FEWP alone and combined with CADs experienced fewer adverse events of dizziness, headache, dry mouth, nausea, and constipation compared to CADs alone. These data suggest that FEWP may be an effective herbal agent in treating depressive symptoms. The addition of FEWP also enhances antidepressant effects of CADs. FEWP may have a higher safety profile compared to CADs.

Prospective and long-term evaluation of erect penile length obtained with inflatable penile prosthesis to that induced by intracavernosal injection.

We compared erect penile length after inflatable penile prosthesis (IPP) implantation with that induced by in-tracavernosal injection (ICI) before surgery. A total of 11 patients with full erections induced by ICI of 0.25 mL of Trimix (papaverine, phentolamine and prostaglandin E1) at the time of penile color duplex Doppler ultrasonography were enrolled in this study. The patients subsequently underwent IPP implantation as the ultimate treatment for their erectile dysfunction (ED). Erect penile length consequent to IPP implantation was measured at 6 weeks, 6 months and at 1 year after surgery. The Sexual Health Inventory for Men (SHIM) was administered before, and at 6 months and 1 year after IPP implantation. Erect penile length (mean +/- s.e.) as induced by ICI was 13.2 +/- 0.4 cm, whereas the lengths attained with IPP were 12.4 +/- 0.3, 12.5 +/- 0.3 and 12.5 +/- 0.4 cm at the sixth week, sixth month and 1-year follow-ups, respectively. There were 0.83 +/- 0.25, 0.75 +/- 0.20 and 0.74 +/- 0.15 cm decreases in erect penile length at 6 weeks, 6 months and 1 year, respectively, after IPP implantation when compared with that after ICI (P < 0.05). The SHIM scores for patients reporting shorter penises were the same as those for patients without complaints at the 6-month and 1-year follow-ups (P > 0.05). To our knowledge, this is the first study to objectively show a significant decrease in erect penile length after IPP implantation when compared with that after ICI. However, this decrease did not affect the effectiveness of IPP in treating ED.