Improving the understanding of PI-RADS in practice: characters of PI-RADS 4 and 5 lesions with negative biopsy.

The Prostate Imaging Reporting and Data System (PI-RADS) has good ability to identify the nature of lesions on prostate magnetic resonance imaging (MRI). However, some lesions are still reported as PI-RADS 4 and 5 but are biopsy-proven benign. Herein, we aimed to summarize the reasons for the negative prostate biopsy of patients who were assessed as PI-RADS 4 and 5 by biparameter MRI. We retrospectively sorted out the prostate MRI, treatment, and follow-up results of patients who underwent a biparameter MRI examination of the prostate in The First Affiliated Hospital of Nanjing Medical University (Nanjing, China) from August 2019 to June 2021 with PI-RADS 4 and 5 but a negative biopsy. We focused on reviewing the MRI characteristics. A total of 467 patients underwent transperineal prostate biopsy. Among them, biopsy pathology of 93 cases were negative. After follow-up, 90 patients were ruled out of prostate cancer. Among the 90 cases, 40 were considered to be overestimated PI-RADS after review. A total of 22 cases were transition zone (TZ) lesions with regular appearance and clear boundaries, and 3 cases were symmetrical lesions. Among 15 cases, the TZ nodules penetrated the peripheral zone (PZ) and were mistaken for the origin of PZ. A total of 17 cases of lesions were difficult to distinguish from prostate cancer. Among them, 5 cases were granulomatous inflammation (1 case of prostate tuberculosis). A total of 33 cases were ambiguous lesions, whose performance was between PI-RADS 3 and 4. In summary, the reasons for "false-positive MRI diagnosis" included PI-RADS overestimation, ambiguous images giving higher PI-RADS, diseases that were really difficult to distinguish, and missed lesion in the initial biopsy; and the first two accounted for the most.

Associations of waist circumference with sex steroid hormones among 4031 USA children and adolescents.

In the recent decades, obesity rates among children and adolescents, especially males, have increased significantly. This worldwide phenomenon is thought to significantly affect the levels of sex hormones. However, the association between waist circumference (a marker of abdominal obesity) and sex hormone levels in children and adolescents is unknown. In this study, 4031 participants aged 6-19 years from the United States National Health and Nutrition Examination Survey (NHANES) in the USA were enrolled in this study. The common confounders of age, race, body mass index, educational level, family income, diabetes, and time of sample collection were also collected. The participants missing any of the above information were excluded from the study. We used multiple linear regression and other multiple statistics to assess the associations between waist circumference and serum testosterone, estradiol, sex hormone-binding globulin (SHBG), free androgen index (FAI), and testosterone/estradiol ratio (T/E2). Waist circumference remained associated with sex hormone levels in children and adolescents after controlling for covariates. As waist circumference increases, testosterone levels in children and adolescents show an overall decline after a brief increase, with the inflection point for waist circumference of 65-66 cm. In addition, waist circumference positively correlates with estradiol levels in male children (ß = 0.007, 95% confidence interval: 0.004-0.009). Moreover, circulating SHBG decreases in children and adolescents as waist circumference increases. In conclusion, this study highlighted waist circumference as a vital indicator affecting sex hormone levels in children and adolescents.

Prostate-derived IL-1ß upregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis.

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-1ß(IL-1ß) 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-1ß 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-1ß 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-1ß administration. Therefore, we identified IL-1ß 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-1ß upregulates NMDA expression.

[Changes of psychological, erectile and urinary functions of the patients with penile fracture after surgical treatment].

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.

Enhanced Recovery After Surgery and Radical Cystectomy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Enhanced recovery after surgery (ERAS) protocols aim to optimize patient recovery after major surgery. Our study was to examine the evidence of the effectiveness of interventions designed to improve patient outcomes after radical cystectomy. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Medline, Embase, Cochrane from January 2005 to January 2021 without language restrictions. ELIGIBILITY CRITERIA: Randomized and non-randomized controlled studies implementing ERAS measuring its interventions on rates of postoperative complications, 30-day readmission, length of stay (LOS) and bowel function after radical cystectomy. DATA EXTRACTION AND SYNTHESIS: Two members of the investigating team independently selected studies and evaluated bias using the Cochrane collaboration tool. Meta-analysis of all comparative studies used inversed-weighted, fixed- effects models and random effects models to pool results. Publication bias was graphically assessed using contour-enhanced funnel plots and the Egger's test of funnel plot symmetry. RESULTS: Fifteen studies were included in our meta-analysis; we observed that ERAS decreased the time for the first bowel movement (standardized mean difference [SMD]: -1.30, 95% CI -1.90 to -0.70, P<0.00001) and shortened the length of stay (LOS) ([SMD]: -0.49, 95% CI -0.77 to -0.20, (P < 0.00001)); however, 30-day readmission (risk ratio [RR]: 0.97,95% [CI] 0.73 to 1.28, P=0.52) and the overall postoperative complication rate (risk ratio [RR]: 0.98,95% confidence interval [CI]: 0.88 to 1.09, P= 0.41) showed no significant difference.

Upregulated expression of NMDA receptor in the paraventricular nucleus shortens ejaculation latency in rats with experimental autoimmune prostatitis.

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.

Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation.

BACKGROUND: Although some recent neuroimaging studies have indicated the abnormal brain structure or function in patients with lifelong premature ejaculation (LPE), whether and how the abnormal thalamic function participates in processing sexual behavioral information are still unclear in patients with LPE. AIM: The aim of this study was to assess the changes in the thalamus metabolism and structural integrity in patients with LPE. METHODS: We performed a multimodal magnetic resonance approach in a 3.0 T system, including proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging, and volumetric analysis to detect the differences in thalamic metabolism and structure between 20 patients with LPE and 15 healthy controls. OUTCOMES: We analyzed and correlated the clinical symptoms of the subjects with significant 1H-MRS-based features. Peak areas of N-acetylaspartate, choline, creatine (Cr), and glutamate/glutamine (Glu) were calculated with the LCModel software. RESULTS: Diffusion tensor imaging and volumetric analysis of thalami showed no differences between the 2 groups. On the contrary, 1H-MRS study disclosed that both Glu concentrations and Glu/Cr ratio values in the thalami of patients with LPE were remarkably increased when compared with healthy controls (P < .01 for both variables). In addition, both the intravaginal ejaculatory latency time score and Chinese Index of Sexual Function for Premature Ejaculation-5 score were negatively related to increased Glu concentrations and Glu/Cr ratio values. CLINICAL IMPLICATIONS: Glutamatergic activity changes of thalamus may be an underlying indicator for evaluating sensory conduction efficiency in patients with LPE. STRENGTHS & LIMITATIONS: The present study first found the abnormal thalamic metabolism in patients with LPE and contributed to a better understanding of the LPE etiology. Limitations include a cross-sectional study design with small samples and no examination of other brain areas. CONCLUSION: Our findings show that the increase in glutamatergic activity of thalamus is related to LPE, suggesting that the increased Glu neurotransmission in the thalamus may contribute to the development of premature ejaculation. Xia J-D, Chen F, Zhang Q-J, et al. Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation. J Sex Med 2021;18:275-283.

Inhibitory Role of Gamma-Aminobutyric Receptors in Paraventricular Nucleus on Ejaculatory Responses in Rats.

BACKGROUND: Although abnormal sympathetic nerve system (SNS) activity has been demonstrated in the pathogenesis of ejaculation disorders, few data are available on its underlying mechanism. AIM: To investigate whether differences in ejaculatory behavior of rats were associated with the state of SNS activity and gamma-aminobutyric (GABA) receptor expressions in the paraventricular nucleus (PVN) of the hypothalamus and the effects of GABA receptors in the PVN on ejaculatory behavior. METHODS: Based on ejaculatory performance, Sprague-Dawley rats were divided into "sluggish," "normal," and "rapid" ejaculators. PVN microinjection was performed to evaluate the role of GABA receptors on sexual behavior. OUTCOMES: The outcomes include differences in expression and distribution of GABA receptors and norepinephrine level among the 3 groups and changes in copulation behavior parameters after PVN microinjection. RESULTS: Compared with "normal" rats, the "rapid" group ejaculated more times with shorter latency (P < .001, P < .001) and had lower expression and distribution of both GABA-A and GABA-B receptors, while the opposed results appeared in the "sluggish" group. The norepinephrine level was successively increased among "sluggish," "normal," and "rapid" rats (P < .001) and correlated with ejaculation frequency (r = 0.896, P < .001) and ejaculation latency (r = -0.835, P < .001). In addition, bilateral microinjection of the GABA-A and GABA-B receptor agonist (isoguvacine and baclofen) into the PVN both significantly prolonged the intromission latency and inhibited ejaculation, which could be blocked by antagonist gabazine and CGP-35348, respectively. Vigabatrin, the GABA-transaminase inhibitor, caused a significantly reduced ejaculation frequency and extended ejaculation latency in rats, which could be offset by simultaneous injections of gabazine and CGP-35348. CLINICAL IMPLICATIONS: Our findings provide new understanding about GABA receptors in the PVN on sexual behavior and enhance the comprehension of neurobiological mechanisms involved in premature ejaculation. STRENGTHS & LIMITATIONS: Our results have indicated that GABA receptors in the PVN may inhibit ejaculation through restraining the activity of SNS. However, our study did not analyze the changes of GABA receptors in other brain areas, which needs further study. CONCLUSION: Ejaculation behaviors in male rats are associated with SNS activity and could be regulated by GABA receptors in the PVN, which may be of assistance in the treatment of ejaculation disorders in the future. Zhang QJ, Yang BB, Yang J, et al. Inhibitory Role of Gamma-Aminobutyric Receptors in Paraventricular Nucleus on Ejaculatory Responses in Rats. J Sex Med 2020;17:614-622.

MMP-8 C-799 T, Lys460Thr, and Lys87Glu variants are not related to risk of cancer.

BACKGROUND: Several studies have focused on the relationship between MMP-8 variants and cancer risk, but they have been unsuccessful in drawing reliable conclusions. METHODS: We employed odds ratio (OR) together with 95% confidence interval (CI) to assess the correlation between MMP-8 C-799 T, Lys460Thr, and Lys87Glu polymorphisms and cancer risk. We further employed in silico tools to evaluate the effect of MMP-8 expression on cancer susceptibility and overall survival time. RESULTS: A total of 8140 patients with malignant carcinoma and 10,529 healthy individuals (control) were enrolled. Overall, the analysis showed that the relationship between three MMP-8 variants and cancer susceptibility was not significant (allelic contrast, C-799 T: OR = 0.98, 95% CI = 0.92-1.04, Pheterogeneity = 0.068; Lys460Thr: OR = 0.94, 95% CI = 0.67-1.32, Pheterogeneity = 0.905; Lys87Glu: OR = 1.05, 95% CI = 0.93-1.18, Pheterogeneity = 0.968). Similar results were observed in subgroup analysis by ethnicity, cancer type, and source of control. In silico analysis indicated that MMP-8 expression was elevated in bladder cancer tissue compared to that in the control. However, both the higher and lower MMP-8 expression groups did not show an impact on the overall survival time of the patients. CONCLUSIONS: MMP-8 C-799 T, Lys460Thr, and Lys87Glu variants are not participant with the susceptibility of cancer.

Effects of mu opioid receptors in paraventricular nucleus on ejaculation through mediating sympathetic nerve system activity.

To investigate the roles of mu opioid receptors (MORs) in paraventricular nucleus of the hypothalamus (PVN) on ejaculation and its underlying mechanism in the rats, we performed copulation behavioral testing and acute experiments. During the acute experiments, mean arterial pressure (MAP), heart rate (HR), bulbospongiosus muscle-electromyogram (BSM-EMG) and pressure of vas deferens (PVD) were all recorded. The expression levels and distributions of opioid receptors were also assessed in PVN of male rats. Moreover, adeno-associated virus type 1 (AAV1) was microinjected into PVN to demonstrate whether there are direct projections from PVN to lumbar spinothalamic (LSt) cells. We found that microinjection of MOR agonist, D-A1a2-NM9-Phe4-Gly(ol)5enkephalin (DAGO), into the PVN prolonged the intromission latency and inhibited ejaculation (P = 0.0241, P = 0.0473, respectively), while the opposed results appeared in CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, MOR antagonist) group (P = 0.0021, P = 0.0286, respectively). Moreover, DAGO caused a significant decrease in MAP and HR (P = 0.0065, P = 0.0030, respectively), and PVD decreased significantly after DAGO microinjection in PVN (P = 0.0383). CTAP not only blocked the effect of DAGO but also significantly increased MAP, HR and PVD (P = 0.0003, P = 0.0010, P = 0.0074, respectively). Meanwhile, a significant increase was observed in BSM-EMG activity after microinjecting of CTAP (P = 0.0022), accompanied by visible BSM contraction. Additionally, anterograde monosynaptic transneuronal tracer AAV1 labeling revealed that neurons in PVN projected directly to LSt cells in L3-4 spinal cord. These results indicate that MORs in PVN centrally mediate ejaculation by regulating the sympathetic outflow, which may be treated as a therapeutic target for ejaculation disorders in the future.

Robotic-assisted partial nephrectomy with sequential clamping of segmental renal arteries for multiple ipsilateral renal tumors: initial outcomes.

BACKGROUND: To assess the technical feasibility and outcomes of robotic-assisted partial nephrectomy (RPN) with sequential segmental renal artery (SRA) clamping for multiple ipsilateral renal tumors (MIRTs). METHODS: From April 2016 to February 2018, consecutive eleven cases successfully underwent RPN with sequential SRA clamping under the guidance of dual-source computed tomography (DSCT). RESULTS: Ten cases had two lesions and two cases had three at the ipsilateral kidneys. The mean size and the mean R.E.N.A.L score for the dominant lesion of single case were 3.3 cm and 5.7, respectively. Twenty-two lesions (84.6%) had one target SRA and four (15.4%) had two target SRAs. Satisfactory ischemic areas were achieved by sequentially clamping two (81.8%) or three (18.2%) target SRAs with mean clamping time of 18.8 (15.0-27.0) min for single lesion, and the mean of total clamping time for single case was 37.5 (32.0-52.0) min. Only the complications of grade 1-2 were found and no positive surgical margin was discovered. The mean follow-up time was 5.4 months and no local recurrence or metastasis was found. The mean postoperative eGFR was 71.2 ml/minute/1.73m2 that was only an insignificant reduction (9.3%) compared with the preoperative baseline. CONCLUSION: This novel nephron-sparing technique, RPN with sequential SRA clamping, represents a good alternative for selected patients with MIRTs. With the guidance of DSCT and skilled robotic experience, this technique is feasible and can maximize renal function preservation. Large-scale multicenter clinical studies are still needed to further prove these initial outcomes.

VEGF gene rs3025039C/T and rs833052C/A variants are associated with bladder cancer risk in Asian descendants.

INTRODUCTION: Polymorphisms of vascular endothelial growth factor (VEGF) gene were evaluated in a number of studies to evaluate bladder cancer (BCa) susceptibility but with controversial conclusions. MATERIAL AND METHODS: We performed a pooled analysis and used odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) to investigate the correlation between VEGF gene rs3025039C/T and rs833052C/A variants and risk of BCa. Furthermore, we utilized in silico tools to demonstrate the relationship of VEGF expression correlated with BCa susceptibility and survival time. RESULTS: A total of eight studies including 4359 BCa patients and 5417 control subjects were enrolled in our study. For VEGF rs3025039C/T, a significant association was indicated between this variant and BCa risk in homozygote comparison (OR = 1.51; 95% CI = 1.13-2.02; P heterogeneity = 0.815) and recessive genetic model (OR = 1.49; 95% CI = 1.12-1.99; P heterogeneity = 0.874), in particular in an Asian population subgroup. For VEGF rs833052C/A, we observed a positive association between this variant and BCa susceptibility in Asian descendants. Results from in silico tool showed evidence that VEGF expression in bladder carcinoma tissue is higher than that in normal counterpart (transcripts per kilobase million = 7.21 vs 6.85; P < 0.05). CONCLUSIONS: The VEGF gene rs3025039C/T and rs833052C/A variants may contribute to the risk of developing BCa, especially in Asian descendants. Future larger sample studies should be continued to focus on this issue in more detail.

Robotic renal cyst decortication with calyceal diverticulectomy in a toddler - technical practicalities: a case report.

BACKGROUND: Incidence of simultaneous renal cyst with calyceal diverticula in contralateral kidney is rare in children. A minimally invasive procedure in different sittings is often recommended. CASE PRESENTATION: A Chinese 15-month-old boy presented to the Urology department of a tertiary care center with right flank pain. He was subjected to magnetic resonance urography and was diagnosed as having right renal cyst and contralateral calyceal diverticula. He underwent robotic cyst decortication and calyceal diverticulectomy using da Vinci robot. His postoperative period was uneventful. He was discharged on fifth postoperative day. Histopathology was consistent with simple renal cyst. CONCLUSIONS: Robotic combined cyst decortication and contralateral diverticulectomy is feasible in selected small children. However, it demands adequate technical skill and experience.

[Clinical application of the disposable vasographic interventional therapy kit in vasoseminal vesiculography].

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.

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.

[Outcomes of micro-TESE combined with ICSI for non-obstructive azoospermia].

OBJECTIVE: To investigate the clinicaleffects of micro-dissection of testicular sperm extraction (micro-TESE) and its combination with intracytoplasmic sperm injection (ICSI) in the treatment of non-obstructive azoospermia (NOA). METHODS: We retrospectively analyzed the clinical data on 130 NOA patients treated between December 2015 and December 2017, including36 cases of idiopathic NOA, 22 cases of idiopathic NOA with small testis, 18 cases of Klinefelter syndrome, 46 cases of surgically treated cryptorchidism and 8 cases of AZFc microdeletion.All the patients underwent micro-TESE and 29 of them with sperm received micro-TESE + ICSI. We observed the changes in the postoperative serum T level, analyzed the influences of different types of NOA and testicular pathology on the sperm retrieval rate (SRR) and the outcomes of ICSI. RESULTS: All the micro-TESE operations were successfully completed. The SRR was significantly higher in those surgically treated for cryptorchidism (60.9%) than in the other NOA groups (P<0.05), withstatistically significant differencesnot among the latter groups (P>0.05) but among differenttypes of testicular pathology (P<0.05), the highest in the hypospermatogenesis group (100%), very low in those with Sertoli-cell-only syndrome (11.8%), and the lowest in the cases of spermatogenesis arrest (0). The serum T level was remarkably decreased at 1 and 6 months after operation (P<0.01), but markedly higher at 6 than at 1 month (P<0.01). Of the 52 patients with sperm retrieved at micro-TESE, 29 of their spouses received ICSI, resulting in 17 pregnancies, 6 live births, and 6 spontaneous abortions. CONCLUSIONS: Micro-TESE is an effective method for the treatment of NOA, and its combination with ICSI can help the NOA patients obtain their genetic offspring.

An Up-to-date Meta-analysis of Coffee Consumption and Risk of Prostate Cancer.

PURPOSE: Results of the association between coffee consumption (CC) and the risk of prostate cancer (PC) are still controversy. Based on published relevant studies, we conducted an up-to-date meta-analysis to investigatethis issue. MATERIALS AND METHODS: The protocol used in this article is in accordance with the PRISMA checklist. Eligible studies were screened and retrieved by using PUBMED and EMBASE as well as manual review of references up to July 2016. We calculated the pooled relative risk (RR) with 95% confidence interval (CI) with random effect models. The dose-response relationship was assessed by generalized least-squares trend estimation analysis. RESULTS: Totally, we included twenty-eight studies (14 case-control and 14 cohort studies) on CC with 42399 PC patients for the final meta-analysis. No significant association of PC was found for high versus non/lowestCC, with RR = 1.07 (95% CI: 0.96-1.18). In subgroup meta-analysis by study design, there were no significant positive associations between CC and PC in case-control studies (RR = 1.19, 95% CI: 1.05-1.35) or in the cohort studies (RR = 0.97, 95% CI: 0.84-1.12). Additionally, RR with different quality of studies were respectively 1.15 (95% CI: 0.99-1.34) and 1.28 (95% CI: 1.03-1.58) for high and low quality in the case-control studies; while were respectively 1.02 (95% CI: 0.88-1.20) and 0.81 (95% CI: 0.57-1.14) in the cohort studies. When analyzed by geographic area, we found no association between CC and PC, with RR = 1.06 (95% CI: 0.86-1.30) for 10 studies from Europe, 1.06 (95% CI: 0.94-1.20) for 13 studies conducted in America; 1.12 (95% CI: 0.70-1.79) for 4 studiesfrom Asia. However, in subgroup analysis by subtype of the disease, there was a significant negative (beneficial) association in the localized PC (RR = 0.90, 95% CI: 0.84-0.97), but not for the advanced PC (RR = 0.90, 95%CI: 0.70-1.16). Additionally, RR = 0.99 (95% CI: 0.98-0.99) for an increment of one cup per day of coffee intake shows significant association with the localized PC. CONCLUSION: Our results indicate that CC has no harmful effect on PC. On the contrary, it has an effect on reducing the localized PC risk. Further prospective cohort studies of high quality are required to clarify this relationship.

Targeting AXL overcomes resistance to docetaxel therapy in advanced prostate cancer.

Resistance to docetaxel is a major clinical problem in advanced prostate cancer. The overexpression of AXL receptor tyrosine kinase (AXL) has been correlated with chemotherapeutic drug resistance. However, the role of AXL expression in docetaxel resistance in prostate cancer is yet unclear. In this study, we demonstrate that AXL is overexpressed and activated independent of Gas6 in docetaxel-resistant prostate cancer cells (PC3-DR and DU145-DR). Moreover, we show that forced overexpression of AXL in PC3 and DU145 cells is sufficient to induce resistance to docetaxel in these cell lines. Notably, genetic or pharmacologic inhibition of AXL in the resistant models suppressed cell proliferation, migration, invasion, and tumor growth, and these effects were significantly augmented when AXL inhibition was combined with docetaxel treatment. Mechanistically, we found that AXL inhibition led to reversion of the epithelial-mesenchymal transition (EMT) phenotype and decreased the expression of ATP-binding cassette B1 (ABCB1). Overall, our results identify AXL as an important mediator of docetaxel resistance in prostate cancer. We propose that AXL-targeted therapy, in combination with docetaxel, has the potential to improve the response to docetaxel therapy and reduce resistance induced by prolonged docetaxel therapy in prostate cancer.

Multivariate model for predicting semen cryopreservation outcomes in a human sperm bank.

Semen cryopreservation is widely used in assisted reproductive technologies, but it reduces sperm quality dramatically. The aim of this study was to develop a model using basal semen quality to predict the outcome of postthaw semen parameters and improve the efficiency of cryopreservation in a human sperm bank. Basal semen parameters of 180 samples were evaluated in the first stage, and a multiple logistic regression analysis involving a backward elimination selection procedure was applied to select independent predictors. After a comprehensive analysis of all results, we developed a new model to assess the freezability of sperm. Progressive motility (PR), straight-line velocity (VSL) and average path velocity (VAP) were included in our model. A greater area under the receiver operating characteristic curve was obtained in our model when compared with other indicators. In the second stage of our study, samples that satisfied the new model were selected to undergo freeze-thawing. Compared with the first stage, the rate of good freezability was increased significantly (94% vs 67%, P = 0.003). By determining basal semen quality, we have developed a new model to improve the efficiency of cryopreservation in a human sperm bank.

[Expression of AXL enhances docetaxel-resistance of prostate cancer cells].

OBJECTIVE: To explore the effect of the AXL expression on the chemosensitivity of prostate cancer PC-3 and DU145 cells to docetaxel and possible mechanisms. METHODS: Using Western blot, we examined the expressions of the AXL protein, p-AXL and Gas6 in the docetaxel-resistant PC-3 (PC-3-DR) and DU145 (DU145-DR) cells stimulated with gradually increased concentrations of docetaxel. We transfected the PC-3 and DU145 cells with negative NC ShRNA and AXL-ShRNA, respectively, which were confirmed to be effective, detected the proliferation, apoptosis and cycle distribution of the cells by CCK8, MTT and flow cytometry after treated with the AXL-inhibitor MP470 and/or docetaxel, and determined the expression of the ABCB1 protein in the PC-3-DR and DU145-DR cells after intervention with the AXL-inhibitor R428 and/or docetaxel. RESULTS: The expression of the AXL protein in the PC-3 and DU145 cells was significantly increased after docetaxel treatment (P <0.05). The expressions AXL and p-AXL were remarkably higher (P <0.05) while that of Gas6 markedly lower (P <0.05) in the PC-3 and DU145 than in the PC-3-DR and DU145-DR cells. The inhibitory effect of docetaxel on the proliferation and its enhancing effect on the apoptosis of the PC-3 and DU145 cells were significantly decreased at 48 hours after AXL transfection (P <0.05). MP470 obviously suppressed the growth and promoted the apoptosis of the PC-3-DR and DU145-DR cells, with a higher percentage of the cells in the G2/M phase when combined with docetaxel than used alone (P <0.05). R428 markedly reduced the expression of ABCB1 in the PC-3-DR and DU145-DR cells, even more significantly in combination with docetaxel than used alone (P <0.05). CONCLUSIONS: The elevated expression of AXL enhances the docetaxel-resistance of PC-3 and DU145 prostate cancer cells and AXL intervention improves their chemosensitivity to docetaxel, which may be associated with the increased cell apoptosis in the G2/M phase and decreased expression of ABCB1.