Altered brain activity associated with premature ejaculation improved by electroacupuncture in rats.

Background: Premature ejaculation (PE) is linked with abnormal brain activity that is modifiable by electroacupuncture (EA). Aim: In this study we aimed to explore the central pathological mechanism underlying EA in treating PE. Methods: Six-week-old male Sprague-Dawley rats were divided into a PE group (n = 8) and a control group (n = 8) according to ejaculatory frequency during copulatory behavior. All rats underwent EA at the Zusanli acupoint (ST-36) for 4 weeks. Magnetic resonance imaging data were collected before and after EA. Outcomes: The behavioral parameters, plasma norepinephrine levels, fractional amplitude of low frequency fluctuation (fALFF), and regional homogeneity (ReHo) were evaluated. Results: The PE group ejaculated more times with shorter latency compared with controls. After EA, the ejaculation frequency of the PE group decreased, and the ejaculation latency period increased, with no changes observed in the control group. Norepinephrine levels were higher in the PE group than in the controls and were positively correlated with ejaculation frequency and negatively correlated with ejaculation latency. The PE group showed lower fALFF in the right striatum and higher ReHo in the brainstem compared with controls. After EA, controls showed decreased fALFF in the right striatum, left olfactory bulb, and dorsal fornix and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, prelimbic system, right basal forebrain region, septal region, and olfactory bulb, while the model group exhibited increased fALFF in the right hypothalamic region, decreased fALFF in the left globus pallidum and right basal forebrain region and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, olfactory bulb, basal forebrain region, dentate gyrus, right dysgranular insular cortex, and striatum. Compared with the controls after EA, the model group showed increased ReHo of the right hypothalamic region and decreased ReHo of the right dysgranular insular cortex. Clinical Implications: These findings might enhance the understanding of PE and contribute to new, targeted therapies for PE. Strengths and Limitations: The therapeutic effects might be achieved by EA inhibiting the activity in brain regions involved in ejaculatory behavior. However, the curative effect of acupuncture might be underestimated due to some curative effects of sham acupuncture used in the control group. Conclusion: In conclusion, the ejaculatory frequency of rats may be reduced and ejaculation latency could be extended by EA at ST-36, which might be achieved by the effects of this treatment on brain activity.

Rapid ejaculator rats are more susceptible to anxiety compared with normal ejaculator rats.

By observation of Sprague-Dawley male rats with different ejaculatory behaviors, we have identified distinct behavioral characteristics in rapid ejaculator rats. To validate these differential behaviors, we conducted multifaceted behavioral experiments on rapid ejaculator rats and normal rats. Through mating experiments, 42 male rats were categorized into 5 rapid ejaculator rats, 29 normal ejaculator rats, and 8 sluggish ejaculator rats according to their ejaculation frequency. We selected 5 rats exhibiting rapid ejaculation and 5 rats with normal ejaculation for participation in the Morris water maze, open-field test, and balance beam experiments. The open-field tests revealed that rapid ejaculator rats spent shorter time in the center region (1.23 ± 1.21 vs. 6.56 ± 2.40 s, P = 0.0041), less entered the center region (0.80 ± 0.75 vs. 3.40 ± 1.50, time, P = 0.0145), traveled shorter distances (17,003.77 ± 3339.42 vs. 25,037.90 ± 5499.94 mm, P = 0.0371), and had a lower average speed compared with normal rats (66.09 ± 62.36 vs. 195.56 ± 83.41 mm/s, P = 0.0377). However, no significant differences were observed in the Morris water maze and balance beam experiments (0.25 ± 0.05 vs. 0.26 ± 0.07, P = 0.7506;16.40 ± 3.77 vs. 16.25 ± 2.05, P = 0.9515). These behavioral results indicated that the rapid ejaculator rats were more prone to anxiety. To further substantiate this claim, we examined Brain-derived neurotrophic factor expression levels in the hippocampus of rat brains using immunohistochemistry and western blotting. The results demonstrate lower Brain-derived neurotrophic factor expression in the hippocampus of rapid ejaculator rats compared with that in normal rats (P = 0.0093). Thus, our experiments indicate that rapid ejaculator rats exhibit a higher propensity for anxiety, potentially linked to their abnormal neurophysiologic state. It is concluded that rapid ejaculator rats may be more susceptible to anxiety on a pathophysiological basis.

ADSCs labeled with SPIONs tracked in corpus cavernosum of rat and miniature pig by MR imaging and histological examination.

Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in animal models of erectile dysfunction. However, few studies have been carried out using a reliable in vivo imaging method to trace transplanted cells in real time, which is necessary for systematic investigation of cell therapy. The study aims to explore the feasibility of non-invasively monitoring intracavernous injection of ADSCs in rat and miniature pig corpus cavernosum using in vivo magnetic resonance (MR) imaging. Thirty-six male Sprague Dawley rats (10 weeks old) and six healthy, sexually mature male miniature pigs (20 kg weight) were obtained. ADSCs were isolated from paratesticular fat of donor rats and cultured. Then ADSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs), a type of MR imaging contrast agent, before transplantation into rats and pigs. After intracavernous injection, all rats and pigs underwent and were analyzed by MR imaging at the day of ADSC transplantation and follow-up at 1, 2 and 4 weeks after transplantation. In addition, penile histological examination was performed on all rats and pigs before (n = 6) and at 1 day (n = 6), 1 week (n = 6), 2 weeks (n = 6) or 4 weeks (n = 12) after ADSC transplantation. SPION-labeled ADSCs demonstrated a strong decreased signal intensity compared with distilled water, unlabeled ADSCs or agarose gel. SPION-labeled ADSCs showed a hypointense signal at all concentrations, and the greatest hypointense signal was observed at the concentration of 1 × 106. MR images of the corpus cavernosum showed a hypointense signal located at the injection site. T2*-weighted signal intensity increased over the course of 1 week after ADSCs transplantation, and demonstrated a similar MR signal with that before ADSCs transplantation. After SPION-labeled ADSC injection, T2*-weighted MR imaging clearly demonstrated a marked hypointense signal in pig corpus cavernosum. The T2*-weighted signal faded over time, similar to the MR imaging results in rats. Obvious acute inflammatory exudation was induced by intracavernous injection, and the T2*-weighted signal intensity of these exudation was higher than that of the injection site. The presence of iron was detected by Prussian blue staining, which demonstrated ADSC retention in rat corpus cavernosum. Lack of cellular infiltrations were demonstrated by H&E staining before and 4 weeks after transplantation, which indicated no negative immune response by rats. Prussian blue staining was positive for iron oxide nanoparticles at 2 weeks after transplantation. SPION-labeled ADSCs showed a clear hypointense signal on T2-weight MRI in vitro and in vivo. The MR signal intensity in the corpus cavernosum of the rats and miniature pigs faded and disappeared over time after ADSC transplantation. These findings suggested that MR imaging could trace transplanted ADSCs in the short term in the corpus cavernosum of animals.

Abnormal cortical surface-based spontaneous and functional connectivity in the whole brain in lifelong premature ejaculation patients.

Recent research has highlighted structural and functional abnormalities in the cerebral cortex of patients with premature ejaculation (PE). These anomalies could play a pivotal role in the physiological mechanisms underlying PE. This study leveraged functional magnetic resonance imaging (fMRI), a noninvasive technique, to explore these neural mechanisms. We conducted resting-state fMRI scans on 36 PE patients and 22 healthy controls (HC), and collected data on Premature Ejaculation Diagnostic Tool (PEDT) scores and intravaginal ejaculation latency time (IELT). Employing a surface-based regional homogeneity (ReHo) approach, we analyzed local neural synchronous spontaneous activity, diverging from previous studies that utilized a volume-based ReHo method. Areas with significant ReHo differences between PE and HC groups underwent surface-based functional connectivity (FC) analysis. Significant discrepancies in ReHo and FC across the cortical surface were observed in the PE cohort. Notably, PE patients exhibited decreased ReHo in the left triangular inferior frontal gyrus and enhanced ReHo in the right middle frontal gyrus. The latter showed heightened connectivity with the left lingual gyrus and the right orbital superior frontal gyrus. Furthermore, a correlation between ReHo and FC values with PEDT scores and IELT was found in the PE group. Our findings, derived from surface-based fMRI data, underscore specific brain regions linked to the neurobiological underpinnings of PE.

The application of intraoperative neurophysiological monitoring in selective dorsal neurotomy for primary premature ejaculation: a prospective single-center study.

Selective dorsal neurotomy (SDN) is a surgical treatment for primary premature ejaculation (PE), but there is still no standard surgical procedure for selecting the branches of the dorsal penile nerves to be removed. We performed this study to explore the value of intraoperative neurophysiological monitoring (IONM) of the penile sensory-evoked potential (PSEP) for standard surgical procedures in SDN. One hundred and twenty primary PE patients undergoing SDN were selected as the PE group and 120 non-PE patients were selected as the normal group. The PSEP was monitored and compared between the two groups under both natural and general anesthesia (GA) states. In addition, patients in the PE group were randomly divided into the IONM group and the non-IONM group. During SDN surgery, PSEP parameters of the IONM group were recorded and analyzed. The differences in PE-related outcome measurements between the perioperative period and 3 months' postoperation were compared for the PE patients, and the differences in effectiveness and complications between the IONM group and the non-IONM group were compared. The results showed that the average latency of the PSEP in the PE group was shorter than that in the normal group under both natural and GA states (P < 0.001). Three months after surgery, the significant effective rates in the IONM and non-IONM groups were 63.6% and 34.0%, respectively (P < 0.01), and the difference in complications between the two groups was significant (P < 0.05). IONM might be useful in improving the short-term therapeutic effectiveness and reducing the complications of SDN.

Cobalt-Catalyzed Asymmetric Alkylation of (Hetero)Arenes with Styrenes.

An efficient and general intermolecular Cobalt(II)-catalyzed asymmetric alkylation of styrenes with (hetero)arenes including indoles, thiophene and electron rich arenes has been developed, providing straightforward access to enantioenriched alkyl(hetero)arenes with high enantioselectivity. Mechanistic studies suggest that the reaction underwent a CoH-mediated hydrogen atom transfer (HAT) with alkenes, followed by a pivotal catalyst-controlled SN 2-like pathway between in situ generated organocobalt(IV) species and aromatic nucleophiles. This is the first CoH-catalyzed asymmetric hydrofunctionalization using carbon nucleophiles, providing a new strategy for asymmetric Friedel-Crafts type alkylation.

Genetic analysis and intracytoplasmic sperm injection outcomes of Chinese patients with congenital bilateral absence of vas deferens.

PURPOSE: Congenital bilateral absence of the vas deferens (CBAVD) is a major cause of obstructive azoospermia and male factor infertility. CBAVD is mainly caused by mutations in the genes encoding CFTR (cystic fibrosis transmembrane conductance regulator) and ADGRG2 (adhesion G protein-coupled receptor G2). This study aimed to describe CFTR and ADGRG2 variations in 46 Chinese CBAVD patients and evaluated sperm retrieval and assisted reproductive technology outcomes. METHODS: The CFTR and ADGRG2 genes were sequenced and analyzed by whole-exome sequencing (WES), and variations were identified by Sanger sequencing. Bioinformatic analysis was performed. We retrospectively reviewed the outcomes of patients undergoing sperm retrieval surgery and intracytoplasmic sperm injection (ICSI). RESULTS: In total, 35 of 46 (76.09%) patients carried at least one variation in CFTR, but no copy number variants or ADGRG2 variations were found. In addition to the IVS9-5 T allele, there were 27 CFTR variations, of which 4 variations were novel and predicted to be damaging by bioinformatics. Spermatozoa were successfully retrachieved in 46 patients, and 39 of the patients had their own offspring through ICSI. CONCLUSION: There are no obvious hotspot CFTR mutations in Chinese CBAVD patients besides the IVS9-5 T allele. Therefore, WES might be the best detection method, and genetic counseling should be different from that provided to Caucasian populations. After proper counseling, all patients can undergo sperm retrieval from their epididymis or testis, and most of them can have their own children through ICSI.

Positive effects of the inclusion of open-mouth pressure for elimination of blood in microscopic subinguinal varicocelectomy.

PURPOSES: Primary varicocele (PVC) may cause testicular hypofunction and scrotal pain. We believe that the currently used procedure microscopic subinguinal varicocelectomy (MSV) can be further improved to provide more benefits to the patients. METHODS: In total, 100 patients who were diagnosed as having PVC grade II or III with venous reflux based on ultrasound results, along with scrotal pain and visible scrotal varicose veins, were enrolled; they were randomly divided into two groups. When the experimental group underwent MSV, stagnant venous blood in the internal spermatic vein close to the testis was drained using manual pressure, whereas the control group was treated with routine MSV procedure. The patients' psychological condition, symptoms, prognoses, scrotal appearances, and other related indexes were evaluated before and after the surgeries, and the results were compared. RESULTS: Scores on days 1-3 after the surgeries were significantly different between the two groups (P < 0.05) for the Hamilton Depression Scale (HAMD) after viewing the scrotum immediately after the surgeries, the Hamilton Anxiety Scale (HAMA) after viewing the scrotum immediately after the surgeries, and the average visual analog scale (VAS). No significant differences were found between the groups for other evaluation indexes (P > 0.05). CONCLUSIONS: The use of open-mouth pressure for elimination of blood reduces postoperative filling of dilated scrotal veins, reduces the visual stimuli to patients immediately after surgery, significantly improves the anxiety and depression of patients, helps to maintain positive mental condition in patients after the surgeries, and increases their confidence in recovery from the disease. It also leads to better pain relief within a short period after the surgery and maximizes surgical benefits for the patients.