DSEATM: drug set enrichment analysis uncovering disease mechanisms by biomedical text mining.

Disease pathogenesis is always a major topic in biomedical research. With the exponential growth of biomedical information, drug effect analysis for specific phenotypes has shown great promise in uncovering disease-associated pathways. However, this method has only been applied to a limited number of drugs. Here, we extracted the data of 4634 diseases, 3671 drugs, 112 809 disease-drug associations and 81 527 drug-gene associations by text mining of 29 168 919 publications. On this basis, we proposed a 'Drug Set Enrichment Analysis by Text Mining (DSEATM)' pipeline and applied it to 3250 diseases, which outperformed the state-of-the-art method. Furthermore, diseases pathways enriched by DSEATM were similar to those obtained using the TCGA cancer RNA-seq differentially expressed genes. In addition, the drug number, which showed a remarkable positive correlation of 0.73 with the AUC, plays a determining role in the performance of DSEATM. Taken together, DSEATM is an auspicious and accurate disease research tool that offers fresh insights.

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.

[Mu-opioid receptors in the paraventricular nucleus regulate ejaculatory behaviors via the sympathetic nerve system in male rats].

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.

Functional materials with self-healing properties: a review.

Self-healing materials (SHMs) have been a research hot topic in recent years owing to their greatly improved longevity and safety in practical applications. Recently, research on SHMs has gradually expanded from structural materials to functional materials. Functional materials with self-healing properties (FMSH) require simultaneous repairing not only of the mechanical properties but of the functionalities from damaged cracks or wounds. It is more challenging to introduce both self-healing properties and a particular functionality to materials owing to the difficulties of preparing the materials and their more complex healing mechanism. Herein, we summarize the recent progress that has been made in FMSH, put forward insights from the perspectives of material preparation and healing mechanisms and highlight future developments for FMSH.

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.

[Glans-preserving surgery for superficial penile squamous cell carcinoma ≥2 cm in diameter].

OBJECTIVE: To explore the feasibility of glans-preserving surgery (GPS) in the treatment of superficial penile squamous cell carcinoma (PSCC) with the lesion diameter of ≥2 cm. METHODS: We retrospectively analyzed the clinical data on 69 cases of superficial PSCC (≤T1aN0) treated by GPS (n = 36) or radical surgery (total or partial penectomy, n = 33) from July 2007 to July 2017. RESULTS: The mean tumor diameter and depth of invasion were 3.16 (2.0－6.0) cm and 0.89 (0.5－2.0) cm in the GPS group and 3.56 (2.0－6.0) cm and 1.89 (0.6－4.0) cm respectively in the radical surgery group. The patients were followed up for 10－102 (mean 42) months, during which, 5 patients in the GPS group developed local recurrence at 40 days and 2, 4, 7 and 9 months postoperatively, again underwent gansectomy, partial penectomy or GPS, and experienced no more recurrence during the follow-up of 54, 34, 39, 66 and 70 months. No local recurrence was observed in the radical surgery group, and none of the 69 patients experienced lymph node metastasis or died during the follow-up. CONCLUSIONS: GPS is safe and efficient for the treatment of superficial PSCC with the lesion diameter of ≥2 cm.

[Biomarkers for predicting the outcome of microdissection testicular sperm extraction for non-obstructive azoospermia patients: A systematic review].

Infertility is a common medical condition which affects nearly 15% of the world population. Non-obstructive azoospermia (NOA) is a most challenging problem inducing male infertility and does not respond to the existing medication. Surgery is the primary method for obtaining sperm from NOA patients, but the outcome of testicular sperm extraction is unpredictable preoperatively. Recently, with the development of detection techniques for male infertility, some new biomarkers have come into notice, which may be of some value in predicting the outcome of microdissection testicular sperm extraction (MTSE) and evaluating male infertility. This article presents an overview of the known biomarkers contributive to the prediction of the outcome of MTSE for NOA patients.

Electromagnetic Wave Absorption Coating Material with Self-Healing Properties.

Electromagnetic wave absorption coatings can effectively minimize electromagnetic radiation and are widely used in the military and civil field. However, even small scratches on the coating can lead to a large decline of absorption ability and bring serious consequences. To enhance the lifetime of electromagnetic wave absorbing coating, a kind of self-healing electromagnetic wave absorbing coating is developed by introducing host-guest interactions between the absorbing fillers and polymer matrix. After being damaged, the cracks on this coating can be healed completely with the aid of small amounts of water. Simultaneously, the electromagnetic absorbing ability of the coating is restored along with the self-healing process.

[Adipose-derived stem cells for the treatment of penile erectile dysfunction: An update].

Adipose-derived stem cells (ADSCs) are pluripotent stem cells isolated from the adipose tissue and have the potential for self-renewal and multi-directional differentiation into neurogenic cells, smooth muscle cells, endothelial cells, and so on. Erectile dysfunction (ED) is a common male sexual dysfunction that has a negative impact on the lives of the patients and their partners. Current treatments of ED include surgery and medication, with oral 5-phosphodiesterase inhibitors as the first-line drugs. However, a small number of the patients are not sensitive to these therapies and cannot be improved or cured pathologically. So far, animal experiments and preclinical trials have confirmed the safety and efficacy of ADSCs, which act on ED though paracrine mechanisms. This review summarizes the advances in the recent 5 years in the studies of ADSCs for the treatment of ED.

[Association of the deleted DAZ gene copy related to gr/gr and b2/b3 deletions with spermatogenic impairment].

OBJECTIVE: To investigate the correlation of the deleted azoospermia (DAZ) gene copy related to gr/gr and b2/b3 deletions in the AZFc region with male spermatogenic impairment. METHODS: This study included 121 infertile men with different de- grees of spermatogenic impairment and 95 healthy donors from the sperm bank. Using PCR, PCR-RFLP, and Y chromosome specific sequence tagged sites (STS) , we analyzed the association of DAZ gene copy deletions related to gr/gr and b2/b3 deletions in the AZFc region with spermatogenic impairment. RESULTS: There were 15 cases of gr/gr deletion (12. 40% ) and 6 cases of b2/b3 deletion (4.96%) in the infertility group as compared with 13 cases of gr/gr deletion (13.68%) and 1 case of b2/b3 deletion (1.05%) in the control. Analysis of the DAZ-specific single nucleotide variant (SNV) loci revealed 11 gr/gr-DAZI/DAZ2 deletions (9.09%), 4 gr/gr-DAZ3/DAZ4 deletions (3.31%), and 6 b2/b3-DAZ1/DAZ2 deletions (4.96%) in the infertile men in comparison with 3 gr/ gr-DAZ1/DAZ2 deletions (3.16%), 10 gr/gr-DAZ3/DAZ4 deletions (10.53%), and 1 b2/b3- DAZ3/DAZ4 deletion (1.05%) in the control. CONCLUSION: Partial deletions of gr/gr and b2/b3 exist in both healthy men and male patients with different degrees of spermatogenic impairment and cannot be considered as a risk factor for spermatogenesis impairment. However, deletions of different DAZ duplicons in gr/gr and b2/b3 deletions have different effects on spermatogenesis. DAZ1/DAZ2 instead of DAZ3/DAZ4 deletions might be associated with spermatogenesis impairment.

[Prognostic factors of penis-sparing surgery for early-stage penile cancer].

OBJECTIVE: To investigate the factors influencing the prognosis of penis-sparing surgery (PSS) for early-stage penile cancer. METHODS: We retrospectively studied the clinical data about 45 cases of early-stage penile cancer treated by PSS from January 2007 to December 2014. We calculated the rate of local recurrence-free survival by the Kaplan-Meier method, and conducted univariate and multivariate COX regression analyses on the relevant factors including the patient's age, marital status, tumor location, tumor size, postoperative sexual life, histological grade, and TNM stage. RESULTS: One-year and three-year local recurrence-free survival rates were 95.5% and 52.2%, respectively. Multivariate analysis demonstrated that the histological grade (P = 0.039) and postoperative sexual life (P = 0.049) were independent factors for the prognosis of PSS. Logistic regression showed the patients age to be significantly associated with histological grade (P = 0.014). CONCLUSION: Histological grade and postoperative sexual life are important independent prognostic factors of PSS for early-stage penile cancer, and the patients age is associated with the prognosis of PSS through its influence on the tumor grade.

[Corporoplasty using autologous tunica vaginalis graft for Peyronie's disease].

OBJECTIVE: To assess the effect of corporoplasty with autologous tunica vaginalis graft in the treatment of Peyronie's disease. METHODS: Ten patients with Peyronie's disease underwent plaque excision and corporoplasty with autologous tunica vaginalis graft. We obtained and compared IIEF-5 scores of the patients before and at 1 and 5 years after operation. RESULTS: After surgery, penile curvature was obviously relieved and all the patients achieved normal penile erection and satisfactory sexual intercourse without erection-related pain or recurrent erectile dysfunction. The mean IIEF-5 score was significantly improved at 1 year (22.40±1.08) and 5 years postoperatively (23.00±1.14) as compared with the baseline, (19.20±2.28) (P<0.05 or 0.01). CONCLUSIONS: Corporoplasty with autologous tunica vaginalis graft is a safe, simple and effective option for the treatment of Peyronie's disease, though its definite efficiency is to be further supported by large-sample clinical studies.

[Aberrant expression of long noncoding RNA in prostate cancer].

Prostate cancer (PCa) is one of the most common malignant tumors as well as a frequent cause of cancer-related mortality in men worldwide. The test of serum markers has dramatically improved the early diagnosis of PCa, but its underlying molecular mechanisms are not yet completely identified. Long noncoding RNA (IncRNA) is emerging as a new player in the PCa paradigm demonstrating its potential roles in both oncogenic and tumor suppressive pathways. LncRNA is frequently aberrantly expressed in the majority of PCa cases. This review highlights recent findings of the aberrant expression of lncRNA in PCa and discusses its novel roles in the diagnosis, prediction, prognosis, metastasis, and potential clinical treatment of PCa.

[Expression ratio of the nerve growth factor receptor TrkA to p75NTR correlates with the clinical stage and pathological grade of prostate cancer].

OBJECTIVE: To investigate the expressions and action mechanisms of nerve growth factor (NGF) receptors TrkA and p75NTR in the oncogenesis and progression of prostate cancer (PCa). METHODS: Using immunohistochemistry, we detected the expressions of TrkA and p75NTR in 62 PCa and 35 benign prostatic hyperplasia (BPH) samples, and conducted statistical analysis on the basis of clinical data. RESULTS: Independent-samples t-test showed that, along with poorer tissue differentiation or higher clinical stage of PCa, the expression of TrkA was significantly up-regulated, that of p75NTR remarkably down-regulated, and the expression ratio of TrkA to p75NTR markedly increased. The TrkA/p75NTR ratio was 0.32 in the BPH, 0.52 in the PCa tissue with Gleason score of 6, 1.65 in the PCa tissue with Gleason score of 7, 5.75 in the PCa tissue with Gleason score ≥ 8, 0.89 in the clinical stage of pT2, 1.5 in pT3 a, 3.75 in pT3b, and 7.00 in pTxN1. CONCLUSION: The abnormally increased expression ratio of TrkA to p75NTR might be one of the essential features of malignant transformation of prostate cells. A higher TrkA/p75NTR expression ratio may be associated with a lower tissue differentiation, a higher clinical stage or Gleason score, and therefore a poorer prognosis.

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.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis by epinephrine sprayed on the papilla.

BACKGROUND AND AIM: Epinephrine sprayed on the papilla may reduce papillary edema and prevent acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to evaluate the effects of localized irrigation with epinephrine saline for prevention of post-ERCP pancreatitis (PEP). METHODS: A total of 941 patients who were scheduled for ERCP were recruited into this study. We randomized the patients to have 20 mL of either 0.02% epinephrine or saline sprayed on the papilla after diagnostic ERCP to prevent post-ERCP pancreatitis. We recorded duct visualization, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. The serum amylase levels were measured at 6, 24 and 48 h after ERCP. We counted the patients of PEPs and compared whether there was significant difference between the pancreatitis group and the no pancreatitis group. RESULTS: A univariate analysis of the explanatory variables between the epinephrine and control groups, the pancreatitis and no pancreatitis groups revealed the treatment to be effective, but most of the groups were not statistically significant. PEPs occurred in 40 of the 941 patients (4.25%), the incidence of pancreatitis tended to be higher in the control group (31/480, 6.45%) than in the epinephrine group (9/461, 1.95%) (P = 0.0086). CONCLUSIONS: Epinephrine sprayed on the papilla may be effective to prevent PEP. Female patients (aged ≥ 18 years and < 35 years) (7/40, 17.5%), common bile duct diameter < 10 mm (27/40, 67.5%), previous cholangitis (3/40, 7.5%), body mass index ≥ 24 (22/40, 55%), and/or serum triglycerides ≥ 5.65 mmol/L (6/40, 15%), might be risk factors for post-ERCP pancreatitis, but are not statistically significant in the study.

[Association of interleukin-23 receptor gene polymorphisms with susceptibility and phenotypes of inflammatory bowel diseases in Jiangsu Han population].

OBJECTIVE: To investigate the possible association of interleukin-23 receptor (IL-23R) polymorphisms with the susceptibility and phenotype of inflammatory bowel diseases (IBD) in Jiangsu Han population. METHODS: We genotyped 178 IBD patients including 135 patients with ulcerative colitis (UC), 43 patients with Crohn's disease (CD), and 134 healthy controls for rs11805303, rs1343151, rs11465804, rs11209032, rs17375018, rs11465788. RESULTS: Comparing with the controls (50.4%), there was a significant increase in the carriage of the T allele of rs11805303 in UC (60.4%)(P = 0.020). In genotype-phenotype correlation of rs17375018 in UC, clinical severity (UCDAI) was associated with the prevalence of the G allele showed a trend to mild activity. Genotype polymorphisms of rs17375018A was observed more in younger than 25 in the genotype-phenotype correlation in CD (41.7% vs 22.0%, P = 0.050, OR = 2.532, 95%CI 0.988 - 6.494), while rs11805303 was associated with age at diagnose and disease lesion (P = 0.039 and 0.044). The risk of extra intestinal manifestation in rs17375018A allele carriers was lower (23.1% vs 46.7%, P = 0.040, OR = 2.917, 95%CI 1.027 - 8.283). CONCLUSIONS: We confirmed the susceptibility of rs11805303 polymorphisms with UC and first demonstrated the genotype-phenotype correlation of rs11805303, rs17375018 with UC, CD in Jiangsu Han population.

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.

Perinatal exposure to bisphenol-A impairs learning-memory by concomitant down-regulation of N-methyl-D-aspartate receptors of hippocampus in male offspring mice.

Bisphenol-A (BPA) has been shown to influence development of the brain and behaviors. The purpose of the present report was to investigate the effects of perinatal exposure to BPA on learning/memory and its mechanism of action, especially focusing on N-methyl-d-aspartate receptor (NMDAR). Perinatal maternal exposure to BPA at 0.5, 5, and 50mg/kg/d significantly extended the escape length to find the hidden platform in Morris water maze, and BPA at 0.5 or 5mg/kg/d markedly decreased the percentage of time spent in the quadrant where the platform had been during training both in postnatal day (PND) 21 and PND 56 mice. The results of passive avoidance test showed that the error frequency to step down from a platform after received footshock was significantly increased, and the latency of the step-down response onto the grid floor 24h after received footshock was obviously reduced by exposure to BPA at 5 and 50mg/kg/d (P<0.01) in the PND 21 offspring or at 50mg/kg/d in the PND 56 offspring (P<0.01). Furthermore, perinatal exposure to BPA significantly inhibited the expressions of NMDAR subunits NR1, NR2A, and 2B in the hippocampus during the development stage, especially in PND 56 mice. The expressions of estrogen receptor beta (ERbeta) in both PND 21 and PND 56 mice were markedly down-regulated by BPA at 0.5, 5, and 50mg/kg/d. These results indicate that perinatal exposure to BPA affects normal behavioral development in both spatial memory and avoidance memory, and also permanently influences the behavior of offspring in adulthood. The inhibition of expressions of NMDAR subunits and ERbeta in hippocampus during postnatal development stage may be involved.