Jiadong Xia

In Vitro Evaluation of Endothelial Progenitor Cells from Adipose Tissue as Potential Angiogenic Cell Sources for Bladder Angiogenesis

Autologous endothelial progenitor cells (EPCs) might be alternative angiogenic cell sources for vascularization of tissue-engineered bladder, while isolation and culture of EPCs from peripheral blood in adult are usually time-consuming and highly inefficient. Recent evidence has shown that EPCs also exist in the adipose tissue. As adipose tissue is plentiful in the human body and can be easily harvested through a minimally invasive method, the aim of this study was to culture and characterize EPCs from adipose tissue (ADEPCs) and investigate their potential for the neovascularization of tissue-engineered bladder. Adipose stromal vascular fraction (SVF) was isolated and used for the culture of ADEPCs and adipose derived stem cells (ADSCs). After SVF was cultured for one week, ADEPCs with typical cobblestone morphology emerged and could be isolated from ADSCs according to their different responses to trypsinization. Rat bladder smooth muscle cells (RBSMCs) were isolated and cultured from rat bladder. RBSMCs exhibited typical spindle-shaped morphology. ADEPCs had higher proliferative potential than ADSCs and RBSMCs. ADEPCs stained positive for CD34, Stro-1, VEGFR-2, eNOS and CD31 but negative for α-SMA, CD14 and CD45. ADSCs stained positive for CD34, Stro-1 and α-SMA but negative for VEGFR-2, eNOS, CD31, CD14 and CD45. RBSMCs stained only positive for α-SMA. ADEPCs could be expanded from a single cell at an early passage to a cell cluster containing more than 10,000 cells. ADEPCs were able to uptake DiI-Ac-LDL, bind UEA-1 and form capillary-like structures in three-dimensional scaffolds (Matrigel and bladder acellular matrix). ADEPCs were also able to enhance the human umbilical vein endothelial cells’ capability of capillary-like tube formation on Matrigel. Additionally, significantly higher levels of mRNA and protein of vascular endothelial growth factor were found in ADEPCs than in RBSMCs. These results suggest the potential use of ADEPCs as angiogenic cell sources for engineering bladder tissue.

Efficacy and safety of local anaesthetics for premature ejaculation: a systematic review and meta-analysis

To assess the efficacy and safety of local anaesthetics for premature ejaculation (PE), a systematic review of the literature was performed using the Cochrane Library, PUBMED and EMBASE. We screened and retrieved the randomized controlled trials on the treatment of PE with local anaesthetics. End points included intravaginal ejaculation latency time (IELT), patient-reported outcome assessments and adverse events. Meta-analyses were conducted with Stata 11.0. In total, seven publications involving 566 patients with local anaesthetics and 388 with placebos strictly met our eligibility criteria. Meta-analyses showed that after the patients were treated with the local anaesthetics, the value of the standardized mean difference of the changes in IELT was 5.02 (95% CI: 3.03-7.00). A higher rate of adverse events occurred compared with placebos (odds ratio: 3.30, 95% CI: 1.71-6.36), but these events were restricted to local side effects. In addition, significantly greater improvement was observed in patient-reported outcomes. In summary, local anaesthetics can prolong IELT and improve ejaculatory control and sexual satisfaction.

Clinical characteristics and penile afferent neuronal function in patients with primary delayed ejaculation

Primary delayed ejaculation (DE) is a relatively uncommon condition and has not been studied broadly. In this study, we aimed to investigate the clinical characteristics and penile afferent neuronal function using somatosensory evoked potentials in patients with primary DE. Twenty‐four patients with primary DE and 24 age‐matched normally potent men were enrolled in this study. Results indicated that patients with primary DE had remarkably higher frequency of masturbatory activity (especially, some with idiosyncratic styles), lower night emissions, longer intravaginal ejaculation latency time (IELT), higher anxiety and depression states (p = 0.010, p = 0.017, p < 0.001, p < 0.001, p < 0.001 respectively). In addition, the mean penile shaft sensory threshold values in the patients were considerably higher than those in the healthy men (p < 0.001). Mean latencies of dorsal nerve somatosensory evoked potential DNSEP were 4.32 ms longer in the DE group than those in the control group (p < 0.001). However, the latencies of glans penis somatosensory evoked potential (GPSEP) between the two group showed no significant difference (p = 0.985). At the same time, in comparison with the control group, the amplitudes of DNSEP were considerably lower in the DE group (p = 0.016), but not in the amplitudes of GPSEP (p = 0.934). This study indicates that the patients with primary DE appear to have penile shaft rather than glans hyposensitivity and hypoexcitability, and adaptation to a certain masturbatory technique (higher and idiosyncratic) may be related to the causes of primary DE, which is also associated with lower night emissions, longer IELT, higher anxiety and depression states.

Sympathetic skin response in patients with primary premature ejaculation

To evaluate the possible role of the autonomic (sympathetic) nervous system function among the patients with primary premature ejaculation (PPE) and determine whether there is an etiological basis for this condition. We performed sympathetic skin response located in the penis (PSSR) in 52 patients with PPE and 46 normally potent men. The latencies and amplitudes of PSSR were measured. The PSSR waveforms were classified into P type and N type according to the waveform characteristics. The waveform distribution in the PPE patients was not statistically different from that in the control group (P=0.609). Mean latency of the PSSR was significantly shorter in the patients than that in the normally potent men (P<0.001). Mean amplitude of the PSSR was significantly greater in patients than that in the normal men (P<0.001). Patients with PPE have hyperactivity of the sympathetic nervous system, which may be another factor involved in the pathological mechanisms of PPE, and the PSSR is an objective test to evaluate patients with PPE.

The Sympathetic Skin Response Located in the Penis as a Predictor of the Response to Sertraline Treatment in Patients with Primary Premature Ejaculation

INTRODUCTION The pathologic mechanisms of primary premature ejaculation (PPE) are complex and multifactorial, and hyperactivity of the sympathetic nervous system is one of the mechanisms. AIM To examine the effects of sertraline on sympathetic nervous system activity and assess the predictive value of the sympathetic skin response located in the penis (PSSR) on the response to sertraline treatment in PPE patients. METHODS Sixty-one patients with PPE were recruited. Each received 50 mg sertraline daily for 8 weeks. Before and after the experiment, the patients were evaluated for PSSR tests and sexual performance parameters. Additionally, based on the latency of PSSR, we divided the patients into a normal PSSR group and an abnormal PSSR group, and compared the sertraline treatment efficacy between the two groups. MAIN OUTCOME MEASURES Changes in intravaginal ejaculation latency time (IELT) and the Chinese premature ejaculation index-5 (CIPE-5), and the latencies and amplitudes of PSSR after sertraline treatment. RESULTS Overall, 58 (95.1%) patients completed the entire study and were analyzed. After the 8-week sertraline treatment, compared with those of pretreatment, IELT and CIPE-5 scores were significantly increased (both P < 0.001), and the amplitudes and latencies of PSSR in the PPE patients were remarkably decreased and prolonged, respectively (both P < 0.001). In addition, the changes of the latencies of PSSR were positively correlated with the increment of IELT (r = 0.375, P = 0.004). The treatment outcome was better in patients with a baseline abnormal PSSR than in those with a baseline normal PSSR (P = 0.021). CONCLUSIONS These results suggest that clinical improvement in response to sertraline in the PPE patients, at least in part, is mediated through reducing sympathetic nervous system activity indexed by PSSR. Measurement of the PSSR appears to provide useful information for predicting treatment responses in the PPE patients.

A reassessment of penile sensory pathways and effects of prilocaine–lidocaine cream in primary premature ejaculation

To assess the penile sensory pathway abnormalities of the patients with primary premature ejaculation (PPE) and effects of prilocaine–lidocaine (PLA) cream, we enrolled 82 PPE patients and 34 normal potent male volunteers. Somatosensory evoked potentials of dorsal nerve (DNSEP) and glans penis (GPSEP) were performed in each subject. In addition, among the 82 patients, 60 were selected and randomly divided into PLA and placebo subgroups, each with 30 patients. Cream was applied evenly on the glans penis for 10 min and washed off just before DNSEP and GPSEP were repeatedly measured. Mean latencies of DNSEP and GPSPE were both remarkably shorter in the patients than those in the normal potent men (P<0.001, both). Compared with the control group, the mean amplitudes of GPSEP were significantly greater in the patient group (P<0.001), but not considerably on the amplitudes of DNSEP (P=0.229). After cream application, the latencies and amplitudes of both DNSEP and GPSEP were significantly prolonged and reduced, respectively, in the PLA cream subgroup (P<0.001, all). These results showed that hyperexcitable ejaculatory reflex neurological factor was linked to PPE, because of hypersensitivity of the penile, accelerated conduction and cortical amplification of the genital stimuli. The PLA cream could delay sensory latency and decrease glans penile hyperexcitability, which may be the mechanism for PPE treatment.

Association of 370-371insACA, 494T>C, and 1423C>T haplotype in ubiquitin-specific protease 26 gene and male infertility: a meta-analysis

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.

Somatosensory evoked potentials assess the efficacy of circumcision for premature ejaculation.

To assess the efficacy and mechanism of circumcision in the treatment of premature ejaculation (PE) with redundant prepuce, we enrolled a total of 81 PE patients who received circumcision. The patients’ ejaculatory ability and sexual performances were evaluated before and after circumcision by using questionnaires (Intravaginal ejaculation latency time (IELT), Chinese Index of PE with 5 questions (CIPE-5) and International Index of Erectile function- 5 (IIEF-5)). Furthermore, somatosensory evoked potentials (SEPs) including dorsal nerve (DNSEP) and glans penis (GPSEP) of the patients were also measured. The mean IELTs of preoperation and post operation were 1.10±0.55 and 2.48±2.03 min, respectively (P<0.001). In addition, the geometric mean IELT after operation was 2.16 min, compared with the baseline 1.07 min before the operation, the fold increase of the IELT was 2.02. Compared with the uncircumcised status, scores of CIPE-5 showed a significant increase after circumcision (P<0.001). The mean latencies (and amplitudes) of GPSEP and DNSEP were 38.1±4.0 ms (3.0±1.9 uV) and 40.5±3.4 ms (2.8±1.6 uV) before circumcision, respectively; and 42.8±3.3 ms (2.8±1.6 uV) and 40.5±4.1 ms (2.4±1.2 uV) in the follow-up end point after circumcision. Only the latencies of GPSEP showed significant prolongation before and after circumcision (P<0.001). The ejaculation time improvement after circumcision is so small, and equal to placebo response, therefore it could not be interpreted as a therapeutic method in men with PE.

No effect of abstinence time on nerve electrophysiological test in premature ejaculation patients

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.

Differences in sympathetic nervous system activity and NMDA receptor levels within the hypothalamic paraventricular nucleus in rats with differential ejaculatory behavior

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.