Single-cell sequencing provides insights into the landscape of ovary in PCOS and alterations induced by CUMS.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder related to psychological distress. However, the mechanism underlying increased prevalence of depression in PCOS remained unclear. This study aimed to explore the unique transcriptional landscape of ovary and offered a platform to explore the mechanism of PCOS, as well as the influences caused by depression. The PCOS rat model was established by letrozole whereas PCOS rat model with depression was established by letrozole combined with chronic unpredicted mild stress (CUMS). Then single-cell RNA sequencing (scRNA-Seq) was applied to analyze the transcriptional features of rat ovaries. Granulosa cells (GCs) and fibroblasts (Fibros) accounted for the top two clusters of total 12 cell types. There were nine clusters in GCs, related to inflammatory response, endoplasmic reticulum (ER) stress, and steroidogenesis. The expression of differentially expressed genes (DEG) Hes1 was higher in PCOS and PCOS + CUMS groups, exhibiting enhanced expression by pseudotime and positively related to inflammation. Pseudotemporal analysis revealed that inflammation contributed to the different GCs distributions. Moreover, analysis of DEGs and gene ontology (GO) function enrichment revealed CUMS aggravated inflammation in PCOS GCs possibly via interferon signaling pathway. In theca cells (TCs), nine clusters were observed and some of them were relevant to inflammation, ER stress, and lipid metabolism. DEGs Ass1, Insl3, and Ifi27 were positively related to Cyp17a1, and Ces1d might contribute to the different trajectory of TCs. Subsequent scRNA-seq revealed a signature profile of endothelial cells (ECs) and Fibros, which suggest that inflammation-induced damage of ECs and Fibro, further exacerbated by CUMS. Finally, analysis of T cells and mononuclear phagocytes (MPs) revealed the existence of immune dysfunction, among which interferon signaling played a critical role. These findings provided more knowledge for a better understanding PCOS from the view of inflammation and identified new biomarkers and targets for the treatment of PCOS with psychological diseases.NEW & NOTEWORTHY In this study, we mapped the landscape of polycystic ovary syndrome (PCOS) ovary with rat model induced by letrozole and provided a novel insight into the molecular mechanism of PCOS accompanied by chronic unpredicted mild stress (CUMS) at single-cell transcriptomic level. These observations highlight the importance of inflammation in the pathogenesis of PCOS, which might also be the bridge between PCOS and psychological diseases.

[Exploring the mechanisms of Jujing pill on varicocele-associated male infertility via network pharmacology and molecular docking technology].

OBJECTIVE: To investigate the potential mechanism of treating varicocele-associated male infertility with Jujing pill using network pharmacology and molecular docking technology. METHODS: The TCMSP and BATMAN databases were used to search for the Chinese medicine components of the Jujing pill and obtain the corresponding targets. The databases GeneCards, DISGENET, OMIM, and HPO were searched for 'varicocele' and 'male infertility' to identify the potential targets of varicocele-associated male infertility. Wayne diagrams were drawn using the jvenn tool to determine the intersection targets of the Chinese medicine targets and disease targets. The intersecting targets were further analyzed to identify the components and Chinese medicine corresponding to them. A Chinese medicine-active ingredient-target network map was constructed in Cytoscape 3.8.2. The protein-protein interaction (PPI) network of the intersecting targets was constructed using the STRING platform. The intersecting targets were imported into the DAVID database for GO enrichment analysis and KEGG-based pathway enrichment analysis. The KEGG database was used to select the most relevant pathway to the topic, and a KEGG pathway map was constructed using the mapper tool. The top 15 pathways with FDR values and their related targets and components were used to draw a core ingredient-target-pathway map. Finally, molecular docking was performed to verify the protein receptors and small molecule ligands of the core genes, and the results were visualized using AutoDock and PyMol software. RESULTS: A total of 207 ingredients and 1103 predicted targets of Jujing pill were screened. Additionally, 285 targets of varicocele were also identified. By using a Venn diagram, 86 common targets were obtained. The analysis of Gene Ontology (GO) results revealed significant enrichment in various biological processes (BP) such as positive regulation of gene expression, positive regulation of transcription, positive and negative regulation of apoptotic processes, response to hypoxia, response to estradiol, and positive regulation of nitric oxide biosynthesis processes. Furthermore, significant enrichment in cellular components (CC) was observed in macromolecules, cytoplasm, nucleus, and phosphatidylinositol 3-kinase complex. In terms of molecular function (MF), enrichment was found in enzyme binding, identical protein binding, transcriptional co-activator binding, and others. KEGG analysis demonstrated enrichment in pathways related to cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, FoxO signaling pathway, and more. Molecular docking results indicated that the core ingredients exhibited a strong binding capacity with the key targets. Conclusion： The effective active ingredients of Jujing pill exert their therapeutic effects on varicocele-associated male infertility through multiple targets and pathways. These findings provide a theoretical basis for future cell and animal experiments to verify the mechanism of action of Jujing pill in treating varicocele-associated male infertility.

[Personality characteristics of erectile dysfunction patients with different traditional Chinese medicine syndromes].

OBJECTIVE: To explore the correlation between personality characteristics and traditional Chinese medicine (TCM) syndromes in ED patients. METHODS: We collected the general demographic data from 97 ED patients with different types of TCM syndromes, including the syndromes of liver-qi depression, fear-induced kidney injury, vital gate fire declination, heart and spleen deficiency, downward diffusion of damp-heat, yin-deficiency and fire-hyperactivity, and blood vessel stasis and obstruction. Using the Eysenck Personality Questionnaire (EPQ), we analyzed the personality types of the patients by comparing their EPQ scores with those of the adult males in the national norm group. RESULTS: Statistically significant differences were found between the ED patients and the males in the national norm group in the EPQ scores on neuroticism (11.97 ± 5.58 vs 4.61 ± 2.93, P < 0.01) and extraversion-introversion (10.06 ± 3.66 vs 7.38 ± 2.85, P < 0.01). Different personality types were significantly associated with the TCM syndrome types of the ED patients (P < 0.01), choleric temperament and melancholic temperament correlated with the syndrome of liver-qi depression (P < 0.01), and sanguine temperament with that of fear-induced kidney injury (P < 0.01). CONCLUSION: TCM syndrome differentiation has underlying correlations with personality characteristics. It is clinically feasible to divide ED into more subtypes based on correlation of the TCM syndrome differentiation with personality characteristics of the patient.

[Action mechanism of Professor Xu Fusong's Shuilu Erxian Dan in the treatment of premature ejaculation: An exploration based on network pharmacology and molecular docking technology].

OBJECTIVE: To analyze the potential action mechanism of Shuilu Erxian Dan in the treatment of premature ejaculation based on network pharmacology. METHODS: The TCMSP database was searched for the main chemical constituents of Euryale and golden cherry, the core components of Shuilu Erxian Dan. Oral bioavailability and medicinal properties were set as the parameters for screening active components, premature ejaculation-related disease targets retrieved from the DisGeNET, GeneCards, OMIM and TTD databases, the common targets of drug pairs and diseases identified with the Wayne diagram, and a drug-active ingredient-target-disease network map constructed with the software Cytoscape. A PPI network map designed through the STRING platform, the website Metascape used for GO and KEGG analyses of the common targets, and the protein receptors and small molecular ligands of the core genes employed for molecular docking and PyMOL visualization. RESULTS: A total of 7 chemical constituents and 171 predictive targets, 1 918 premature ejaculation targets and 113 common targets were identified. GO analysis showed significant enrichment of BP in response to toxic substances and inorganic substances, CC in membrane raft and plasma membrane protein complex, and MF in transcription factor binding and kinase binding. KEGG analysis manifested markedly enriched TNF signaling pathway, JAK-STAT signaling pathway and Cocaine addiction. The results of molecular docking exhibited a good binding energy between the core gene and the component. CONCLUSION: Network pharmacology has revealed the potential action mechanism of Shuilu Erxian Dan in the treatment of premature ejaculation, which has paved the theoretical ground for verification of the effectiveness of Shuilu Erxian Dan in the treatment of premature ejaculation via animals and cells.

[Correlations between resting-state brain functional characteristics and TCM syndrome in premature ejaculation patients with heart-kidney disharmony].

OBJECTIVE: To investigate the correlation between the characteristics of resting-state brain function and the types of traditional Chinese medicine (TCM) syndrome in premature ejaculation (PE) patients with heart-kidney disharmony, and the pathogenesis of abnormal ejaculation of the patients. METHODS: We enrolled 33 PE patients with heart-kidney disharmony and 32 healthy controls matched in general demographic data, evaluated the severity of the main and concurrent symptoms of PE using the PE Diagnostic Tool (PEDT) and TCM Syndrome Scale (TCMSS), and obtained the brain structural and functional MRI data. We processed the collected data and calculated the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF) and regional homogeneity (Reho) of the brain with the DPABI software. Using the REST software package, we compared the significantly different brain areas between the PE and control groups by two-sample t-test and corrected the results for multiple comparisons by AlphaSim, followed by Pearson correlation analysis of ALFF, fALFF and Reho in abnormal brain areas and the PEDT and CMSS scores of the patients. RESULTS: The PE patients showed decreased ALFF values in the bilateral inferior temporal gyrus, left middle frontal gyrus and left orbital part of the inferior frontal gyrus, and increased ALFF values in the bilateral hippocampus, thalamus and precuneus, right inferior occipital gyrus, right calcarine and left inferior parietal, with positive correlations of the ALFF values of the left thalamus with the scores on PEDT (r = 0.35, P < 0.05) and TCMSS (r = 0.44, P < 0.05). The fALFF values of the patients were also decreased in the left temporal pole of the middle temporal gyrus and left anterior cingulate gyrus, but increased in the left inferior temporal gyrus. The Reho values of the patients were decreased as well in the right inferior temporal gyrus, left middle frontal gyrus, right dorsolateral superior frontal gyrus, right middle occipital gyrus, right middle occipital gyrus and right precuneus, but increased in the left temporal pole of the middle temporal gyrus, left middle frontal gyrus and left superior frontal gyrus, with negative correlations between the Reho value of the right superior parietal gyrus and TCMSS scores (r = －0.35, P < 0.05). CONCLUSION: Abnormal brain regions were found in PE patients with heart-kidney disharmony, with might be the pathologically associated with PE symptoms and heart-kidney disharmony of the patients.

[Changes in the functional connectivity of the thalamus in insomniac ED patients with yin deficiency and fire syndrome: An exploration based on functional MRI findings].

OBJECTIVE: To investigate the changes of nocturnal erectile function and functional connectivity (FC) of bilateral thalami in insomniac ED patients with yin deficiency and fire syndrome. METHODS: We enrolled 30 healthy controls and 87 ED patients with yin deficiency and fire syndrome, 41 with and the other 46 without insomnia. Using IIEF-5 and Pittsburgh Sleep Quality Index (PSQI), we evaluated the nocturnal erectile function and sleep quality of the patients and compared the clinical indicators between the two groups. Then we collected and preprocessed the MRI data on the cerebral function of the 15 ED patients with insomnia, another 15 without insomnia and the 30 healthy controls. With the thalamus as the region of interest (ROI), we calculated and compared the FC values of brain regions between the ED patients (with or without insomnia) and healthy controls, and corrected the results for multiple comparisons using the AlphaSim method. RESULTS: Compared with the patients without insomnia, those with insomnia had a lower duration of erectile episode and tumescence and rigidity activity units in the tip of the penis. With the left thalamus as the ROI, the right middle frontal gyrus and inferior parietal were shown to be the differential brain regions among the three groups. Compared with the healthy controls, the patients without insomnia showed decreased FC values between the left thalamus and left orbital part of the middle frontal gyrus, insula, putamen and right thalamus, while those with insomnia exhibited decreased FC values between the left thalamus and bilateral middle frontal gyri, inferior parietal, calcarine fissure, parahippocampal gyrus, left superior parietal gyrus, right precuneus and inferior temporal gyrus, and they also exhibited decreased FC values between the left thalamus and middle frontal gyrus in comparison with those without insomnia. With the right thalamus as the ROI, the left medial superior frontal gyrus, bilateral calcarine fissure and right thalamus were found to be the differential brain regions among the three groups. Compared with the healthy controls, the patients without insomnia showed decreased FC values between the right thalamus (including the right thalamus itself) and left medial orbital superior frontal gyrus, superior temporal gyrus (temporal pole), middle temporal gyrus, insula and right orbital part of the inferior frontal gyrus, while those with insomnia manifested decreased FC values between the right thalamus and middle frontal gyrus, inferior parietal, left superior parietal gyrus and calcarine fissure, and they also manifested increased FC values between the right thalamus and medial superior frontal gyrus, and decreased FC values between the right thalamus and left calcarine fissure in comparison with those without insomnia. CONCLUSION: ED patients with insomnia have more serious clinical symptoms, with FC changes in the thalamocortical loop, which might be the pathological mechanisms of ED with insomnia.

Graph theory analysis reveals premature ejaculation is a brain disorder with altered structural connectivity and depressive symptom: A DTI-based connectome study.

Recent research has shown that premature ejaculation (PE) is associated with negative psychological effects (e.g., depression) and the decline of control over ejaculation is accompanied by structural and functional abnormalities in specific brain areas and connections. However, little is known about the alterations of topological organization in the brain network of patients with PE and its relationship with depressive symptom. We acquired diffusion tensor images, sexual function and depression assessment in 16 lifelong PE patients with depressive symptom, 16 lifelong PE patients without depression and 32 age- and education-matched healthy controls (HC). The differences in nodal centrality and different hub regions among the three groups were compared. Correlation analyses were conducted between the nodal centrality of brain regions displaying significant group differences and the clinical parameters of PE patients. PE patients with depression had increased nodal degree in the right middle frontal gyrus (orbital part) (ORBmid.R) (survived FDR-correction) compared with HC and PE without depression. PE patients with depression also had increased nodal degree in the left and right posterior cingulate gyrus (PCG.L; PCG.R) compared with HC. In addition, PE with depression had increased nodal betweenness in ORBmid.R compared with HC and PE without depression. Moreover PE with depression had decreased nodal participation in the right rolandic operculum (ROL.R), postcentral gyrus (PoCG.R) and supramarginal gyrus (SMG.R) compared with HC, and had decreased nodal participation in ROL.R and the right inferior parietal gyrus (IPL.R) compared with PE without depression, while PE without depression had increased nodal participation in the left precuneus (PCUN.L) compared with HC. The degree and betweenness of ORBmid.R were positively correlated with the total scores of Beck depression inventory (BDI) while the participation of IPL.R had a negative association with the total scores of BDI. Different hubs were found among PE patients with and without depression and HC based on nodal degree, betweenness and participation; however, no significant group differences were found in the frequency distribution of high-degree hubs, high-betweenness hubs, provincial hubs and connector hubs. These findings demonstrated that PE was a brain disorder with altered structural connectivity pattern of brain network and depressive symptom, which suggested that altered structural connectivities of the fronto-cingulate-parietal control network were core neurobiological features associated with PE and depression. Together, these alterations could prove helpful for understanding the pathophysiological mechanisms of PE in depression.

Impaired frontal-parietal control network in chronic prostatitis/chronic pelvic pain syndrome revealed by graph theoretical analysis: A DTI study.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by chronic pain in pelvic area and lower urinary tract symptoms (LUTS). Previous neuroimaging studies demonstrated that chronic pain was associated with the altered brain activity. However, the pathological mechanisms associated with altered brain control of CP/CPPS are not well-understood. Therefore, we sought to investigate the topological properties of white matter brain networks in patients with CP/CPPS and whether the topological configuration of frontal-parietal control network was disrupted. We collected 19 patients with CP/CPPS and 32 matched healthy controls (HCs). Diffusion tensor imaging data of all participates were used to map the white matter structural networks. Graph theoretical method was applied to investigate the alterations of topological properties of brain network in patients. Moreover, we also investigated whether the alerted brain regions might be correlated with any clinical features of patients by the method of Pearson correlation analysis. Both CP/CPPS patients and HCs exhibited a 'small-world' behavior or economical small-world architecture of the white matter brain networks. In addition, CP/CPPS had a lower global efficiency in the right middle frontal gyrus (orbital part) and a higher global efficiency in the left middle cingulate and paracingulate gyri. CP/CPPS also showed increased local efficiency in the left middle cingulate and paracingulate gyri and paracentral lobule. Moreover, the local efficiency of the left middle cingulate gyrus was positively correlated with the scores of the influence of symptoms on the quality of life. The local efficiency of the left precuneus and right supplementary motor area were positively correlated with the total scores of NIH-CPSI and the scores of pain and discomfort symptoms, respectively. Together, we found that patients with CP/CPPS had alterations of connections within the frontal-parietal control network, which suggested that the altered connectivity involved in the executive control processing procedures might contribute to the pathogenesis of the pelvic pain and LUTS in CP/CPPS. Thus these results provided new insights into the understanding of CP/CPPS.

Increased attentional network activity in premature ejaculation patients with anxiety revealed by resting-state functional magnetic resonance imaging.

Psychological account hypothesizes that premature ejaculation (PE) is a learned pattern of rapid ejaculation maintained by anxiety about sexual failure, whereas neuropsychological accounts hypothesizes that PE is the result of dysfunction of central nervous system regulating ejaculatory. However, the central neural mechanism underlying PE patients with anxiety remains unclear. Resting-state functional magnetic resonance imaging (fMRI) data were collected in 20 PE (diagnoses based on PE Guidelines drafted by the International Society for Sexual Medicine [ISSM]) patients with anxiety and 25 matched healthy controls (HCs) from January 2019 to December 2020. The values of fractional amplitude of low-frequency fluctuation (fALFF) were compared between groups. Moreover, the correlations between fALFF and the severity of PE and anxiety of patients were examined. PE patients with anxiety had increased fALFF values in the right inferior frontal gyrus (opercular part) and middle frontal gyrus. In addition, significant positive correlations were found between the scores of PE diagnostic tool (PEDT) and fALFF values of the right inferior frontal gyrus (opercular part), as well as the right middle frontal gyrus. Moreover, fALFF values of the right inferior frontal gyrus (opercular part) and middle frontal gyrus were positively correlated with the scores of self-rating anxiety scale (SAS). Our results suggested that increased attentional network activity might play a critical role in the neural basis of PE patients with anxiety.

[Acupoint application combined with virtual reality technology to relieve pain after circumcision in children].

OBJECTIVE: To explore the effect of acupoint application combined with virtual reality (VR) technology in relieving pain after circumcision in children. METHODS: Using a random number table, we divided 106 children undergoing circumcision into a control and an intervention group of an equal number, the former receiving routine nursing care, and the latter acupoint application combined with VR technology. We compared between the two groups the postoperative pain scores with the Changhai pain ruler, the Hamilton Anxiety Scale (HAMA) scores, and the satisfaction of the patients and their families. RESULTS: Compared with the controls, the patients in the intervention group showed a significantly lower HAMA score (ï¼»2.94 ± 0.98ï¼½ vs ï¼»1.06 ± 0.92ï¼½, P < 0.05) and postoperative pain score (ï¼»5.96 ± 1.24ï¼½ vs ï¼»3.66 ± 1.18ï¼½, P < 0.05), but higher satisfaction in the patients and their families (86.79% vs 98.11%, P < 0.05). CONCLUSIONS: Acupoint application combined with VR technology for children after circumcision has the advantages of effectively relieving the anxiety of the patients, distracting their attention, increasing the pain perception threshold, reducing the perception of pain, improving the satisfaction of the patients and their family members.

[Pressing acupuncture therapy combined with auricular pressure beans for the treatment of chronic prostatitis / chronic pelvic pain syndrome].

OBJECTIVE: To explore the application value of the pressing acupuncture therapy (PAT) combined with auricular pressure beans in the treatment of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS). METHODS: We selected 50 cases of CP/CPPS confirmed in our Department of Andrology from January to December 2019 and randomly divided them into an observation (n = 25) and a control group (n = 25), the former treated by PAT combined with auricular pressure beans in addition to medication, and the latter with auricular pressure beans in combination with drug therapy, both for 14 successive days. We compared the scores on NIH-CPSI and General Comfort Questionnaire (GCQ) between the two groups of patients before and after treatment. RESULTS: After treatment, the patients in the observation group, compared with the controls, showed a significantly higher total effectiveness rate (92% vs 68%, P < 0.05) and GCQ score (ï¼»95.00 ± 9.39ï¼½ vs ï¼»80.16 ± 9.96ï¼½, P < 0.05), and a lower pain symptom score ( ï¼»6.92 ± 2.34ï¼½ vs ï¼»10.08 ± 2.22ï¼½, P < 0.05), urination symptom score (ï¼»3.16 ± 1.46ï¼½ vs ï¼»4.80 ± 1.19ï¼½, P < 0.05), quality of life score (ï¼»4.68 ± 1.35ï¼½ vs ï¼»6.80 ± 1.71ï¼½, P < 0.05) and total NIH-CPSI score (ï¼»14.76 ± 3.31ï¼½ vs ï¼»23.68 ± 3.05ï¼½, P < 0.05). CONCLUSIONS: The pressing acupuncture therapy, with the advantage of dynamic needle retention with good compliance, can relieve the clinical symptoms of CP/CPPS and improve the life comfort of the patients, and is therefore worthy of further clinical research and application.

[Associations between the efficiency of the brain white matter network and clinical symptoms in patients with type â ¢ B prostatitis].

OBJECTIVE: To investigate the changes in the topological properties of the global and local nodal efficiencies of the brain white matter network in patients with type III B prostatitis, and to analyze the correlation between the information transmission efficiency of different brain regions and pelvic pain. METHODS: We enrolled 19 patients with type Ⅲ B prostatitis and 32 normal controls matched in general demographic data for this study. We assessed the pelvic pain of the patients based on the NIH-CPSI, obtained the structural and diffusion-weighted MR images of the brain, preprocessed the MRI data, constructed the brain structural networks and calculated the topological properties of the nodal local and global efficiencies using the FSL software package and brain connection toolbox. Finally, we compared the topological properties between the two groups by t-test with the SPSS 20 software, performed multiple correction of the values using the false discovery rate (FDR) method, and investigated the associations of the altered brain regions with the NIH-CPSI scores by Pearson correlation analysis. RESULTS: The global efficiency of the orbital part of the right median frontal gyrus in the patients with type Ⅲ B prostatitis, compared with that in the normal controls, was dramatically decreased (0.095 ± 0.046 vs 0.13 ± 0.015, P < 0.01) while that of the left median cingulate gyrus markedly increased (0.16 ± 0.027 vs 0.14 ± 0.019, P < 0.01), which were corrected by FDR. The local efficiency of the left median cingulate gyrus was also remarkably decreased in the patients as compared with that in the controls (0.25 ± 0.075 vs 0.19 ± 0.036, P < 0.01), and so was that of the left paracentral lobule (0.25 ± 0.088 vs 0.17 ± 0.065, P < 0.01), which were corrected by FDR. In the patients, the local efficiencies of the left precuneus (r = 0.46, P = 0.045), right supplementary motor area (r = 0.47, P = 0.043) and left median cingulate gyrus (r = 0.60, P = 0.0065) were positively correlated with the total score of NIH-CPSI, the scores of pain and discomfort symptoms, and the scores of the influence of the symptoms on the quality of life. CONCLUSIONS: The changes of the brain regions in the executive control network of the patient with type Ⅲ B prostatitis might be involved in enhancing his sensitivity to pain and discomfort, and consequently lead to pelvic pain and discomfort.

Brain Functional Biomarkers Distinguishing Premature Ejaculation From Anejaculation by ALFF: A Resting-State fMRI Study.

INTRODUCTION: Premature ejaculation (PE) and anejaculation (AJ) are 2 opposite disorders of male ejaculatory dysfunction. Recent studies have demonstrated that the process of ejaculation is mediated by certain neural circuits in the brain. However, different mechanisms between PE and AJ are still unclear. AIM: Therefore, we used resting-state functional magnetic resonance imaging (fMRI) to explore the underlying neural mechanisms in patients with PE and AJ by measuring the amplitude of low-frequency fluctuations (ALFF). METHODS: Resting-state fMRI data were acquired in 17 PE, 20 AJ patients and 23 matched healthy controls (HC). MAIN OUTCOME MEASURE: Differences of ALFF values among the 3 groups were compared. We also explored the correlations between brain regions showing altered ALFF values and scores of Premature Ejaculation Diagnostic Tool (PEDT) in the PE group. RESULTS: There were widespread differences of ALFF values among the 3 groups, which included left anterior cingulate gyrus, precentral and postcentral gyrus, paracentral lobule, superior temporal gyrus, calcarine fissure, putamen; right postcentral gyrus, paracentral lobule, middle temporal gyrus, putamen. Compared with HC, PE patients had greater ALFF in the right inferior frontal gyrus (opercular part), AJ patients had greater ALFF in the left postcentral gyrus. In addition, PE patients exhibited greater ALFF in the left Rolandic operculum, anterior cingulate gyrus, inferior frontal gyrus (orbital part), putamen, and right putamen when compared with AJ patients, as well as decreased ALFF in the right postcentral gyrus. Moreover, positive correlations were found between ALFF of left postcentral gyrus, inferior frontal gyrus (orbital part), right inferior frontal gyrus (opercular part), and PEDT scores. CLINICAL IMPLICATIONS: The differences in central pathophysiological mechanisms between PE and AJ might be useful for improving the clinical diagnosis of ejaculation dysfunction. STRENGTH & LIMITATIONS: Our results showed that the method of fMRI could identify the differences of ALFF between PE and AJ and that these alterations in ALFF were related to clinical function. However, this was a relatively small sample study, and further multimodal neuroimaging studies with large samples were needed. CONCLUSION: The findings demonstrated that altered ALFF of frontal, parietal cortex, and putamen might help distinguish premature ejaculation from anejaculation. Abnormal function of these brain regions might play a critical role in the physiopathology of ejaculatory dysfunction of patients. Chen J, Yang J, Huang X, et al. Brain Functional Biomarkers Distinguishing Premature Ejaculation From Anejaculation by ALFF: A Resting-State fMRI Study. J Sex Med 2020;17:2331-2340.

Variation in Brain Subcortical Network Topology Between Men With and Without PE: A Diffusion Tensor Imaging Study.

INTRODUCTION: Premature ejaculation (PE) is a highly prevalent male sexual dysfunction. Previous studies have found abnormal activity in the sympathetic nervous system and penile sensory pathway of PE. Few studies have investigated the neural mechanisms underlying PE. AIM: The aim of this study was to examine whether the altered cortico-subcortical network topological properties of the brain white matter structural network could be used to differentiate patients with PE from healthy control (HC) subjects. METHODS: Diffusion tensor images data were collected from 32 patients with PE and 35 HC participants. Then, brain white matter structural networks were reconstructed from image acquisition. MAIN OUTCOME MEASURE: Furthermore, nodal measures were calculated and hub regions were identified using the graph-theoretical methods. RESULTS: For cortical brain regions, increased strength, global efficiency, and decreased shortest path length were found in the right superior frontal gyrus (medial), and superior frontal gyrus (medial orbital) were found in patients with PE. In addition, patients with PE also showed decreased strength in the right rolandic operculum and decreased shortest path length, and increased global efficiency in the right inferior frontal gyrus (triangular part). For subcortical brain structures, patients with PE were associated with decreased shortest path length and increased global efficiency in the left insula and right caudate nucleus. Finally, the results showed that 9 PE-specific hub regions were identified in patients compared with HCs, including 7 cortical regions and 2 subcortical regions. CLINICAL IMPLICATIONS: Our results provide new understanding about the pathology of PE and enhances the understanding of PE pathology. STRENGTH & LIMITATIONS: Our results offer biological markers for understanding the physiopathology of PE. However, our study is a cross-sectional design, longitudinal design studies need to explore the causal relationships between aberrant topological characteristics and PE. CONCLUSION: Our results provide new insights into the neural mechanism of PE involving cortico-subcortical network changes, which could serve as a potential biomarker to differentiate individuals with PE from HCs. Chen J, Yang J, Huang X, et al. Variation in Brain Subcortical Network Topology Between Men With and Without PE: A Diffusion Tensor Imaging Study. J Sex Med 2020;17:48-59.

Dopamine D2 receptors in the basolateral amygdala modulate erectile function in a rat model of nonorganic erectile dysfunction.

Nonorganic erectile dysfunction is a problem with unknown central mechanisms. Changes in brain activity in the amygdala have been observed in human patients. This study aimed to investigate the dopamine system in the basolateral amygdala of male rats with nonorganic erectile dysfunction. We applied chronic mild stress to induce nonorganic erectile dysfunction. After exposure to chronic mild stress, the sucrose consumption test, sexual behaviour test and apomorphine test were used to select depression-like rats with erectile dysfunction as nonorganic erectile dysfunction model rats. The sexual behaviour of these rats after central infusion of a dopamine D1/D2 receptor agonist/antagonist was observed. The expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the basolateral amygdala were also measured. The result of the sucrose consumption test, sexual behaviour test and apomorphine test indicated a successful nonorganic erectile dysfunction model. Central infusion of a dopamine D2 receptor agonist increased intromission ratio in model rats. Lower expression levels of tyrosine hydroxylase and the dopamine D2 receptor in the basolateral amygdala were observed in rats with nonorganic erectile dysfunction. These results suggest that impairment of the dopamine D2 receptor pathway in the basolateral amygdala may contribute to the development of nonorganic erectile dysfunction.

[Brain magnetic resonance imaging in exploring the central neurophysiological mechanisms of penile erection: Progress in studies].

Previous studies have found that penile erection is not only dependent on the peripheral nervous and vascular systems, but also controlled by the central nervous system. Some brain regions are responsible for promoting and suppressing penile erection, respectively. Studies on the brain functions showed both activation and inactivation of the brain regions when receiving sexual stimulation, and those on the brain structure of ED patients revealed atrophy of the gray matter structure and abnormal connection of the white matter fibers. In addition, abnormal connections within emotional, cognitive and default and salience networks were found in patients with psychogenic ED. This article reviews the brain MRI-based studies on the central neurophysiological mechanisms of penile erection, aiming to gain a deeper insight into human neurophysiological mechanisms of the neural circuits controlling erectile function.

[Psychological factors and penile blood supply in patients with erectile dysfunction].

OBJECTIVE: To explore the psychological factors and blood supply to the penis in ED patients. METHODS: From August to November 2018, we obtained Symptom Checklist 90 (SCL-90) scores and conducted an Eysenck Personality Questionnaire (EPQ) investigation among 106 ED patients in our Department of Andrology, followed by the test of intracavernosal injection of the vasoactive agent (ICI-VAA) and color duplex Doppler ultrasonography (CDDU). According to the results of ICI-VAA and CDDU, we divided the patients into a normal and an abnormal group, compared their item and total scores on SCL-90 with the national norm by t-test and analyzed the distribution of personality types in different groups by Chi-square test. RESULTS: The results of ICI-VAA and CDDU showed 42 cases to be normal and the other 64 abnormal. Compared with the normal group, the abnormal cases exhibited significantly decreased peak systolic velocity (PSV) in the left and right corpus cavernosum (ï¼»30.90 ± 6.83ï¼½ vs ï¼»19.39 ± 5.07ï¼½ cm/s, P < 0.01; ï¼»30.74 ± 7.00ï¼½ vs ï¼»18.98 ± 4.57ï¼½ cm/s, P < 0.01), but increased end-diastolic velocity (EDV) in the left corpus cavernosum (ï¼»1.77 ± 2.38ï¼½ vs ï¼»3.21 ± 2.78ï¼½ cm/s, P < 0.01). The ED patients undergoing ICI-VAA and CDDU obtained remarkably higher SCL-90 scores than the national norm on depression (1.70 ± 0.64 vs 1.50 ± 0.59, P < 0.01), anxiety (1.62 ± 0.56 vs 1.39 ± 0.43, P < 0.01), compulsion (1.86 ± 0.61 vs 1.62 ± 0.58, P < 0.01), hostility (1.65 ± 0.66 vs 1.48 ± 0.56, P < 0.01), phobia (1.33 ± 0.45 vs 1.23 ± 0.41, P = 0.02), and psychoticism (1.61 ± 0.55 vs 1.29 ± 0.41, P < 0.01) as well as a higher total score (1.61 ± 0.48 vs 1.44 ± 0.48, P < 0.01). The patients with normal results of CDDU got markedly increased scores on anxiety (1.60 ± 0.53, P < 0.01), compulsion (1.83 ± 0.63, P = 0.02) and psychoticism (1.61 ± 0.48, P < 0.01), and so did those with abnormal results of CDDU on depression (1.73 ± 0.65, P < 0.01), anxiety (1.64 ± 0.59, P < 0.01), compulsion (1.88 ± 0.60, P < 0.01), hostility (1.68 ± 0.75, P < 0.01), phobia (1.35 ± 0.44, P = 0.02), psychoticism (1.61 ± 0.59, P < 0.01) and an increased total score as well (1.63 ± 0.51, P < 0.01). Statistically significant differences were not found in either the item scores or the total score on SCL-90 (P > 0.05), nor in the distribution of the EPQ personality types between the normal and abnormal cases (χ2 = 1.12, P = 0.77). CONCLUSIONS: The personality types of ED patients are mainly phlegmatic and melancholic, and their psychological problems chiefly include depression and anxiety, which are more serious in those with insufficient penile blood supply.

[Correlation of betweenness centrality of the right hemispheric network with ejaculatory function in premature ejaculation patients].

OBJECTIVE: To explore the topological properties of the betweenness centrality of the nodes and edges in the brain white matter network of premature ejaculation (PE) patients and analyze the correlation of the importance of the key brain regions and interregional white matter structural connectivity with the ejaculatory function of the patients.Method: We collected the demographic and clinical data, along with the T1 and MR diffusion tensor imaging (MR-DTI) data, on 18 PE patients and 22 normal controls matched in age, sex and education. After preprocessing of the data obtained, we divided the whole brain into 90 symmetrical cortical and subcortical regions (defined as nodes of the brain network) by automated anatomical labeling, examined the structural connectivity between different brain regions by probabilistic white matter fiber tracking (defined as edges of the brain network), and calculated the betweenness centrality of the nodes and edges using the brain connection toolbox. Then, we performed the Mann-Whitney U test on the betweenness centrality of the nodes and edges, subjected the results to false discovery rate (FDR) correction, and assessed the correlation of the attribute values of between-group differences with the ejaculatory function of the patients. RESULTS: Compared with the normal controls, the PE patients showed a significantly decreased betweenness centrality of the right superior occipital gyrus (SOG) (281.18 ± 255.26 vs 67.78 ± 58.98, Z = －3.49, FDR-corrected P < 0.05), but increased betweenness centrality of the right superior temporal gyrus (STG) (222.91 ± 155.60 vs 557.00 ± 322.65, Z = 3.55, FDR-corrected P < 0.05) and betweeness centrality of the edge between the right rolandic operculum and right insula (4.23 ± 8.39 vs 23.83 ± 23.91, Z = 3.84, FDR-corrected P < 0.05). The betweenness centrality of the right SOG was correlated negatively with the level of difficulty in delaying ejaculation (r = －0.51, P = 0.03) and the probability of ejaculation before expectation (r= －0.61, P = 0.01), while that of the right STG positively with PE-related frustration (r = 0.54, P = 0.02) and the level of concern about PE-related distress of the partner (r = 0.47, P = 0.04). CONCLUSIONS: Abnormalities of structural connections were found in the visual stimulus- and emotion processing-related regions in the right cerebral hemisphere of PE patients, which might be associated with rapid ejaculation or decreased ejaculation control and lead to a series of psychological problems.

Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress.

BACKGROUND: Non-organic erectile dysfunction (noED) at functional imaging has been related to abnormal brain activity and requires animal models for further research on the associated molecular mechanisms. AIM: To develop a noED animal model based on chronic mild stress and investigate brain activity changes. METHODS: We used 6 weeks of chronic mild stress to induce depression. The sucrose consumption test was used to assess the hedonic state. The apomorphine test and sexual behavior test were used to select male rats with ED. Rats with depression and ED were considered to have noED. Blood oxygen level-dependent-based resting-state functional magnetic resonance imaging (fMRI) studies were conducted on these rats, and the amplitude of low-frequency fluctuations and functional connectivity were analyzed to determine brain activity changes. OUTCOMES: The sexual behavior test and resting-state fMRI were used for outcome measures. RESULTS: The induction of depression was confirmed by the sucrose consumption test. A low intromission ratio and increased mount and intromission latencies were observed in male rats with depression. No erection was observed in male rats with depression during the apomorphine test. Male rats with depression and ED were considered to have noED. The possible central pathologic mechanism shown by fMRI involved the amygdaloid body, dorsal thalamus, hypothalamus, caudate-putamen, cingulate gyrus, insular cortex, visual cortex, sensory cortex, motor cortex, and cerebellum. Similar findings have been found in humans. CLINICAL TRANSLATION: The present study provided a novel noED rat model for further research on the central mechanism of noED. STRENGTHS AND LIMITATIONS: The present study developed a novel noED rat model and analyzed brain activity changes based at fMRI. The observed brain activity alterations might not extend to humans. CONCLUSION: The present study developed a novel noED rat model with brain activity alterations related to sexual arousal and erection, which will be helpful for further research involving the central mechanism of noED. Chen G, Yang B, Chen J, et al. Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress. J Sex Med 2018;15:136-147.

Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.

AIM: Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. MATERIALS AND METHODS: Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. RESULTS: Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. CONCLUSIONS: These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.