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Background: Orexins are hypothalamic neuropeptides associated with various neurophysiological activities such as sleep, arousal, and reward. However, there are few studies investigating the relationships between orexin receptors in the paraventricular nucleus and sexual behaviors. Objectives: To explore the roles of orexin receptors in the paraventricular nucleus on sexual behaviors and uncover its potential mechanisms in males. Materials and methods: Orexin A, orexin 1 receptor antagonist SB334867, and orexin 2 receptor antagonist TCS‐OX2‐29 were microinjected into the paraventricular nucleus to investigate the effects of orexin receptors on copulatory behavior testing of C57BL/6 mice. To explore if ejaculation could activate orexin 1 receptor‐expressing neurons in the paraventricular nucleus, fluorescence immunohistochemical double staining was utilized. The levels of serum norepinephrine were measured and the lumbar sympathetic nerve activity was recorded to reflect the sympathetic nervous system activity. Moreover, the bulbospongiosus muscle‐electromyogram was recorded and analyzed. To test whether perifornical/lateral hypothalamic area orexinergic neurons directly projected to the paraventricular nucleus, virus retrograde tracing technology was utilized. Results: Orexin A significantly enhanced sexual performance by shortening the intromission and ejaculation latencies, and increasing the mount and intromission frequencies, while the opposite outcomes appeared with SB334867. However, TCS‐OX2‐29 had no significant effects on sexual behaviors. Moreover, orexin A increased lumbar sympathetic nerve activity and the levels of serum norepinephrine, while SB334867 decreased lumbar sympathetic nerve activity and norepinephrine, which caused a significant decrease in sympathetic nervous system outflow. Meanwhile, a robust increase in the bulbospongiosus muscle‐electromyogram activity was identified after microinjecting orexin A. Furthermore, cFos immunopositive cells were increased and double stained with orexin 1 receptor‐expressing neurons in the mating group. Additionally, the retrograde tracing results demonstrated that orexinergic neurons in the perifornical/lateral hypothalamic area directly projected to the paraventricular nucleus. Conclusions: Orexin 1 receptor in the paraventricular nucleus could influence the ejaculatory reflex via mediating the sympathetic nervous system activity, which might be of great importance in the treatment of premature ejaculation in the future. [ABSTRACT FROM AUTHOR]

Experimental autoimmune prostatitis (EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus (PVN). However, the mechanism has not yet been elucidated. Herein, we screened out the target prostate-derived inflammation cytokines (PDICs) by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid (CSF) between EAP rats and their controls. After identifying the target PDIC, qualified males in initial copulatory behavior testing (CBT) were subjected to implanting tubes onto bilateral PVN. Next, they were randomly divided into four subgroups (EAP-1, EAP-2, Control-1, and Control-2). After 1-week recovery, EAP-1 rats were microinjected with the target PDIC inhibitor, Control-1 rats were microinjected with the target PDIC, while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF (aCSF). Results showed that only interleukin-1β(IL-1β) had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls (P < 0.001) and significantly higher protein concentrations in both the serum (P = 0.001) and CSF (P < 0.001) of the EAP groups compared to the Control groups. Therefore, IL-1β was identified as the target PDIC which crosses the blood-brain barrier, thereby influencing the central nervous system. Moreover, the EAP-1 subgroup displayed a gradually prolonged ejaculation latency (EL) in the last three CBTs (all P < 0.01) and a significantly lower expression of NMDA NR1 subunit in the PVN (P = 0.043) compared to the respective control groups after a 10-day central administration of IL-1β inhibitors. However, the Control-1 subgroup showed a gradually shortened EL (P < 0.01) and a significantly higher NR1 expression (P = 0.004) after homochronous IL-1β administration. Therefore, we identified IL-1β as the primary PDIC which shortens EL in EAP rats. However, further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1β upregulates NMDA expression. [ABSTRACT FROM AUTHOR]

Background: Estimated 30%‐40% of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) suffer from premature ejaculation (PE), which is difficult to cure, but the mechanism is still unknown. Based on the results of our previous clinical studies and animal experiments, we propose that the glutamatergic system dysfunction in the paraventricular nucleus (PVN) may be involved. Methods: To test this hypothesis, we used experimental autoimmune prostatitis (EAP) rats to investigate the effects of CP/CPPS on ejaculation behavior through integrating copulatory behavior testing, neuroelectrophysiologic experiments, and molecular biology technologies. Results: Histological examination of prostate tissue in EAP rats exhibited consistent pathological findings with that in CP/CPPS patients. Behavior testing showed that ejaculation latency (EL) of EAP rats significantly shortened compared with the controls (5.1 ± 1.8 vs 9.1 ± 2.4 min, P <.001). Sympathetic nervous system (SNS) activity testing revealed that EAP rats displayed significantly higher plasma norepinephrine (NE) level (1780 ± 493 vs 1421 ± 453 pg/mL, P =.043) and SNS sensitivity (67.8 ± 9.6 vs 44.6 ± 8.7%, P <.001). Immunohistochemical detection and Western blot analysis both displayed that NR1 subunit expression of N‐methyl‐D‐aspartic acid (NMDA) receptors in the PVN of EAP rats was significantly upregulated (P =.007 and P <.001). Furthermore, the expression of NMDA NR1 subunit positively correlated both with SNS sensitivity (r =.917, P <.001) and prostatic inflammation scores (r =.964, P <.001). Conclusion: This study shows that EAP rats suffer from the same PE symptom as CP/CPPS patients. CP/CPPS‐induced inflammatory‐immune response can significantly upregulate the expression of NMDA receptors in the PVN, which shortening the EL by enhancing SNS sensitivity. However, the exact mechanism of chronic inflammation in the prostate causing the upregulated expression of NMDA receptors needs to be further studied. [ABSTRACT FROM AUTHOR]

A novel gold-catalyzed skeletal rearrangement of 1-[2- (1H-isochromen-3-yl)aryl]ethanones with alcohols to construct a five-membered carbocycle ring onto aromatic systems has been developed. This method serves as the first example of synthesizing inden- 1-ones by a gold-catalyzed skeletal rearrangement strategy. [ABSTRACT FROM AUTHOR]

This mild and general route enables the construction of functionalized 1H-indenes utilizing a visible light photoredox catalysis strategy. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is a common andrological disorder, and traditional oral drugs often fail to achieve satisfactory therapeutic effects. As a new field of biomedicine, stem cell therapy (SCT) has seen a significantly increasing number of researches on its treatment of ED in recent years. Preclinical animal models for the study of ED mainly include the models of diabetes mellitus-, aging-, cavernous nerve injury-, and Peyronie's disease-related ED. Previous studies indicated that SCT improved erectile function through paracrine and was more effective when combined with other therapies than used alone in restoring ED-induced pathological changes. Although clinical trials on SCT have partially proved its safety and effectiveness for the treatment of ED, they were still in the early stages and with relatively small sample sizes. This article summarizes the latest advances in the treatment of ED by SCT.

Objective: To investigate the impacts of surgical treatment of penile fracture on the short- and long-term psychological, erectile and urinary functions of the patient., Methods: Fifty patients with penile fracture underwent surgical treatment in the Emergency Department of our hospital from June 2010 to December 2015. Using the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), IIEF-5 and IPSS, we evaluated the psychological, erectile and urinary functions of the patients at 1 day, 6 months and 18 months after surgery, and analyzed the relationship between psychological and erectile functions as well as the possible factors affecting erectile function postoperatively., Results: Compared with the baseline, significant increases were observed at 6 months after surgery in the SDS score (30.3 ± 4.1 vs 50.7 ± 6.5, P < 0.01) and SAS score (29.9 ± 5.9 vs 55.4 ± 7.7, P < 0.01) but a remarkable decrease in the IIEF-5 score (22.4 ± 1.3 vs 18.4 ± 2.1, P < 0.01). At 18 months, neither SDS (50.7 ± 10.0) or SAS score (54.1 ± 8.7) showed any statistically significant difference from that at 6 months (P > 0.05), but the IIEF-5 score (21.1 ± 2.2) was markedly lower than the baseline (P < 0.01), though higher than that at 6 months (P < 0.01). The IPSS scores at 6 and 18 months exhibited were not significantly different from that preoperatively (P > 0.05). Both the SDS and SAS scores were evidently higher in the patients with severe than in those with mild ED. The body mass index (BMI) and waiting time for surgery were significantly negatively correlated with short- and long-term erectile function of the patients after surgery., Conclusions: Patients with penile fracture may have decreased erectile function after surgery, accompanied with anxiety and depression. The risk factors for ED include BMI and waiting-for-surgery time.

Objective: To explore the effects of the mu-opioid receptor (MOR) in the paraventricular nucleus (PVN) on the ejaculatory behaviors of male rats and its potential mechanisms., Methods: Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) with an inserted catheter, the male animals were observed for mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), ejaculation frequency (EF), post-ejaculation interval (PEI), and intromission ratio (IR). The lumbar sympathetic nerve activity (LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine (NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP., Results: Neither CTAP nor DGAO significantly affected the ML of the male rats (P > 0.05). DGAO remarkably increased IF (P < 0.01) and MF (P < 0.01), prolonged IL (P < 0.01), EL (P < 0.01) and PEI (P < 0.01), and reduced EF (P <0.01) and IR (P < 0.05). On the contrary, CTAP markedly decreased IF (P < 0.01) and MF (P < 0.01), shortened IL (P < 0.01), EL (P < 0.01) and PFI (P < 0.01), and elevated EF (P < 0.01) and IR (P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA., Conclusions: MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation.

The sexual behavior of the male can be described as a series of behavioral transitions eventually leading to ejaculation and sexual satisfaction. The ejaculation itself is extensively regulated by different ejaculation generators. The "spinal ejaculation generator" receives genito-sensory signals through afferent fibers and then informs the brainstem and forebrain via ascending fiber projections. Conversely, the supraspinal areas restrict ejaculations to the optimal moments and circumstances through descending afferent fibers. The messages ascending from the spinal cord reach the interconnected thalami, hypothalami, limbic system and cerebral cortex and are integrated with olfactory information. These brain areas are all related to ejaculation, but the exact facilitatory and inhibitory mechanisms involved have not yet been elucidated hitherto. Both the medial preoptic nucleus and brainstem areas play an important role in the "downward" mechanisms underlying the spinal "release" of an ejaculation. The medial preoptic nucleus is also precisely related to the "sexual rewarding" coming with an ejaculation. Meanwhile, the roles of several neurotransmitters are discussed considering their remarkable effects on ejaculation. This review focuses on the ejaculation-related circuits and neurotransmitters for the purpose of gaining a deeper insight into the mechanisms of ejaculation and providing some theoretical evidence for the study and treatment of ejaculation-related diseases.

Differences in intravaginal ejaculation latency reflect normal biological variation, but the causes are poorly understood. Here, we investigated whether variation in ejaculation latency in an experimental rat model is related to altered sympathetic nervous system (SNS) activity and expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus of the hypothalamus (PVN). Male rats were classified as "sluggish," "normal," and "rapid" ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. The lumbar splanchnic nerve activity baselines in these groups were not significantly different at 1460 ± 480 mV, 1660 ± 600 mV, and 1680 ± 490 mV, respectively (P = 0.71). However, SNS sensitivity was remarkably different between the groups (P < 0.01), being 28.9% ± 8.1% in "sluggish," 48.4% ± 7.5% in "normal," and 88.7% ± 7.4% in "rapid" groups. Compared with "normal" ejaculators, the percentage of neurons expressing NMDA receptors in the PVN of "rapid" ejaculators was significantly higher, whereas it was significantly lower in "sluggish" ejaculators (P = 0.01). In addition, there was a positive correlation between the expression of NMDA receptors in the PVN and SNS sensitivity (r = 0.876, P = 0.02). This study shows that intravaginal ejaculatory latency is associated with SNS activity and is mediated by NMDA receptors in the PVN., Competing Interests: All authors declared no competing interests

The nerve electrophysiological tests may differentiate the treatment of primary premature ejaculation (PPE) in our previous studies. However, no study verifies if the results will be affected by abstinence time. From January to December in 2016, fifty PPE patients ejaculated within 2 min and 28 control subjects were enrolled. The nerve electrophysiological tests, including dorsal nerve somatosensory evoked potential (DNSEP), glans penis somatosensory evoked potential (GPSEP), and penile sympathetic skin response (PSSR), were recorded before and immediately after ejaculation. The abstinence day was not correlated with the latencies of SEPs or PSSR neither in PE group (P = 0.170, 0.064, and 0.122, respectively) nor in control group (P = 0.996, 0.475, and 0.904, respectively). No statistically differences were found in the latencies of SEPs and PSSR before and after ejaculation in PE patients (P = 0.439, 0.537, and 0.576, respectively) or control subjects (P = 0.102, 0.198, and 0.363, respectively). Thus, abstinence time does not interfere with the nerve electrophysiological test, which is stable in determining the nerve function of PPE patients., Competing Interests: All authors declared no competing interests

Objective: To investigate the success rate and safety of percutaneous vasoseminal vesiculography with the disposable vasographic interventional therapy kit (VITK)., Methods: This study included ninety-six 19－65 (mean 43) years old male patients with infertility, hematospermia, seminal vesicle cyst, ejaculatory duct cyst, ejaculatory dysfunction, or vas deferens injury, with disease courses varying from 1 month to 7 years. With an open, multi-centered, single-group, self-controlled design and using the disposable VITK, we treated the patients by percutaneous vasoseminal vesiculography via injection of contrast medium into the vas deferens cavity under local anesthesia., Results: Percutaneous vasoseminal vesiculography was successfully performed in 92 (97.87%) of the patients, which revealed abnormal seminal ducts in 51 cases (54.3%). Among the 28 infertile patients, 3 were found with bilateral and 5 with unilateral vas deferens obstruction. Vesiculitis was detected in 36 (81.8%) of the 44 hematospermia patients and bilateral vas deferens abnormality in 5 (38.5%) of the 13 patients with ejaculatory dysfunction. Transectional damage was observed in 2 patients with vas deferens injury induced by bilateral inguinal hernia repair. Three cases of seminal vesicle cyst and 4 cases of ejaculatory cyst were definitely diagnosed by vasoseminal vesiculography., Conclusions: The disposable vasographic interventional therapy kit, with the advantages of simple operation and high safety, deserves a wide clinical application in vasoseminal vesiculography.

Whether the 370-371insACA, 494T>C, and 1423C>T haplotype in ubiquitin-specific protease 26 (USP26) gene is associated with male infertility is controversial. To clarify this issue, we conducted a meta-analysis based on the most recent studies. Eligible studies were screened by using PubMed and Embase. Pooled odd ratio (OR) with 95% confidence interval (CI) was calculated with fixed effect models. Ten studies with 1603 patients and 2505 controls were included. Overall, the results indicated that there was an association between the haplotype and male infertile risk (OR = 1.74, 95% CI: 1.09-2.77). The OR calculated based on the five studies in Asia and three in Europe was 1.96 (95% CI: 1.05-3.67) and 1.54 (95% CI: 0.75-3.16) respectively, however, the OR was 0.86 (95% CI: 0.05-15.29) based on the two investigations in America. In addition, the data from the patients with azoospermia (AZO) showed an increased pooled OR of 2.35 (95% CI: 1.22-4.50). In contrast, the studies with oligoasthenoteratozoospermia (OAT) exhibited that the pooled OR was 0.97 (95% CI: 0.43-2.16). Our analyses indicate that there is an association of alteration in USP26 with male infertility, especially in AZO and Asian population.