PSMC4 promotes prostate carcinoma progression by regulating the CBX3-EGFR-PI3K-AKT-mTOR pathway.

Proteasome 26S subunit ATPase 4 (PSMC4) could regulate cancer progression. However, the function of PSMC4 in prostate carcinoma (PCa) progression requires further clarification. In the study, PSMC4 and chromobox 3 (CBX3) levels were verified by TCGA data and tissue microarrays. Cell counting kit-8, cell apoptosis, cell cycle, wound healing, transwell and xenograft tumour model assays were performed to verify biological functions of PSMC4 in PCa. RNA-seq, PCR, western blotting and co-IP assays were performed to verify the mechanism of PSMC4. Results showed that PSMC4 level was significantly increased in PCa tissues, and patients with PCa with a high PSMC4 level exhibited shorter overall survival. PSMC4 knockdown markedly inhibited cell proliferation, cell cycle and migration in vitro and in vivo, and significantly promoted cell apoptosis. Then further study revealed that CBX3 was a downstream target of PSMC4. PSMC4 knockdown markedly reduced CBX3 level, and inhibited PI3K-AKT-mTOR signalling. CBX3 overexpression markedly promoted epidermal growth factor receptor (EGFR) level. Finally, PSMC4 overexpression showed reverse effect in DU145 cells, and the effects of PSMC4 overexpression on cell proliferation, migration and clonal formation were rescued by the CBX3 knockdown, and regulated EGFR-PI3K-AKT-mTOR signalling. In conclusion, PSMC4 could regulate the PCa progression by mediating the CBX3-EGFR-PI3K-AKT-mTOR pathway. These findings provided a new target for PCa treatment.

[Clinical observation of dapoxetine combined with percutaneous neuromuscular electrical stimulation in the treatment of primary premature ejaculation].

OBJECTIVE: To investigate the clinical efficacy of dapoxetine combined with transcutaneous neuromuscular electrical stimulation (TNES) in the treatment of primary premature ejaculation. METHODS: A total of 60 patients who met the diagnostic criteria for primary premature ejaculation were selected as study subjects and randomly divided into a dapoxetine group (control group) and a dapoxetine combined with percutaneous neuromuscular electrical stimulation group (observation group).30 patients in each group were treated for 4 weeks. Intravaginal ejaculatory latency time (IELT), the score of Premature Ejaculation Diagnostic Tool (PEDT), sympathetic skin response located in the penis (PSSR), Patient Health Questionnaire (PHQ-9), and Generalized Anxiety Disorder Questionnaire (GAD-7) before and after treatment were recorded in the two groups. Before and after treatment, the difference in observed indexes in the two groups and the comparison of effective rates between the two groups were analyzed. RESULTS: The latency of IELT and PSSR was prolonged and the PEDT score was decreased in both the observation group and the control group, the difference was statistically significant (P<0.01). Compared with the control group, the observation group had statistically significant differences in extending IELT and PSSR latency and reducing PEDT score (P<0.05). The effective rates of the observation group and control group were 90% and 63.33%, respectively, and the difference was statistically significant (P<0.05). There was no significant difference in the improvement of depression and anxiety levels between the two groups (P> 0.05). CONCLUSION: Dapoxetine combined with TNES has a better clinical effect than dapoxetine alone in the treatment of primary premature ejaculation, and can be used as an effective option for clinical treatment of primary premature ejaculation.

[Transcutaneous neuromuscular electrical stimulation for the treatment of erectile dysfunction: A clinical observation].

OBJECTIVE: To observe the clinical efficacy of transcutaneous neuromuscular electrical stimulation (TNES) in the treatment of ED. METHODS: According to the inclusion and exclusion criteria, we included and studied 25 cases of ED treated by TNES in Northern Jiangsu People's Hospital from June 2021 to February 2022 using the self-matched pre- and post-control method. Before and after treatment, we conducted RigiScan penile hardness test under audiovisual sexual stimulation (AVSS) for all the patients and obtained their scores on the Erectile Hardness Scale (EHS), IIEF-5, Premature Ejaculation Diagnostic Tool (PEDT), Patient Health Questionnaire 9 (PHQ-9) and Generalized Anxiety Disorder Questionnaire 7 (GAD-7). RESULTS: No adverse reactions such as pain, allergy, skin burn, and subcutaneous congestion were observed in any of the patients. There were statistically significant differences after treatment in erection time, average and maximum hardness of the penile tip, mean hardness of the penile root, and circumference of the penile tip (P < 0.05), but not in the circumference and maximum hardness of the penile root during erection compared with the baseline (P > 0.05). Significant improvement was observed after treatment in the IIEF-5 score (P < 0.05), with a total effectiveness rate of 68%, as well as in the PEDT score (P < 0.05) GAD-7 anxiety score (P < 0.05), but not in the PHQ-9 depression score (P > 0.05). CONCLUSION: TNES, as a safe and non-invasive therapy, can improve penile hardness under AVSS and the erectile function and anxiety symptoms of ED patients, and can be used as a new option for the treatment of ED.

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms in andrology-a narrative review.

Background and Objective: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism and one-carbon metabolism. MTHFR gene polymorphism affects enzyme activity. MTHFR gene polymorphism is closely related to many human diseases, such as cardiocerebrovascular diseases, diabetes, neural tube defects (NTDs), tumors, and so on. In the field of Andrology, MTHFR gene polymorphism may be associated with male infertility and erectile dysfunction (ED), and there is a possibility of treating male infertility and ED by supplementing with folic acid. However, its exact pathophysiologic mechanism is not fully understood. We sought to obtain a robust understanding of the interactions between MTHFR gene polymorphism, oxidative stress, DNA methylation, hyperhomocysteinemia (HHcy), male infertility, and ED. Methods: We performed a non-systematic literature review using the PubMed database to identify articles specifically related to MTHFR, male infertility and ED. Key Content and Findings: Our literature review on MTHFR gene polymorphism in male infertility patients indicates a significant association between C677T gene polymorphism and male infertility. There is limited literature on the correlation between ED and MTHFR gene polymorphism, and there are two different conclusions, related and unrelated. More clinical data are needed to clarify the conclusion. There is a possibility of using folic acid supplementation to treat male infertility and ED, especially for patients with thymine-thymine (TT) genotype. Future research is necessary to further understand the relationship between MTHFR gene polymorphism and male infertility and ED. Conclusions: Our literature review on MTHFR gene polymorphism in male infertility patients indicates a significant association between C677T gene polymorphism and male infertility. Folic acid supplementation can improve sperm quality. The correlation between MTHFR gene polymorphisms and ED is questionable and needs to be confirmed by more clinical data. MTHFR gene polymorphisms are associated with homocysteine (Hcy) levels, which affects vascular endothelial function and may be related to the development of vascular ED (VED). Folic acid supplementation improves International Index for Erectile Function (IIEF) questionnaire scores in ED patients in whom phosphodiesterase 5 inhibitor (PDE5i) alone is ineffective.

Transcutaneous Neuromuscular Electrical Stimulation for Treating Varicocele-Induced Scrotal Pain.

Varicocele is a prevalent vascular disorder affecting the male reproductive system, leading to scrotal pain and testicular dysfunction. Epidemiological studies have shown that varicocele occurs in approximately 10% to 15% of adult males, while scrotal pain affects 2% to 10% of the population. Currently, clinical treatment options for varicocele-induced scrotal pain include general therapy, medication, and surgery. Among these, surgical intervention is considered the most effective method, boasting a success rate of 80%. However, it carries risks such as postoperative bleeding, infection, and recurrence, making it less desirable for some patients. In recent years, transcutaneous neuromuscular electrical stimulation has gained wide acceptance for treating various andrological conditions, including erectile dysfunction and premature ejaculation, yielding positive outcomes. This non-invasive technique offers a promising alternative for managing varicocele-induced scrotal pain, potentially reducing the need for surgical intervention and its associated risks. Its growing popularity underscores the need for further research and clinical trials to validate its efficacy and safety in treating this condition.

An Electrophysiological Technique to Accurately Diagnose and Treat Erectile Dysfunction.

Erectile dysfunction (ED) is a common disease in males. In the past, the first-line treatment of ED was mainly noninvasive-psychotherapy and oral phosphodiesterase 5 (PDE5) inhibitors. Oral PDE5 inhibitors often need to be used before sexual intercourse and do not repair the pathological damage; hence, the therapeutic effect for secondary ED caused by neurological or endocrine disorders is poor. Second-line treatments mainly include penile corpus cavernosum injection of alprostadil, transurethral administration, vacuum negative pressure devices, and other methods, with obvious side effects such as local pain. The third-line treatment mainly refers to penile prosthesis implantation. Indications of this treatment are strict, complications such as mechanical failure and infection may occur after operation, and it is expensive. Other treatments such as stem cell therapy and gene therapy are still in the experimental research stage and have not been used in clinics. A new treatment based on an electrophysiological technique combines a medical infrared thermal imager with low-frequency (20-50 Hz) neuromuscular electrical stimulation, which has achieved good results in the prevention and treatment of female pelvic floor dysfunction. Male generative organs are located in the pelvic floor area, and their normal function not only depends on the integrity of the structure and function of the male generative organs, but is also closely related to the blood vessels, nerves, muscles, and other pelvic floor organs. Therefore, this electrophysiological technique was applied to male ED, focusing on the observation of the penis, groin, and hypogastrium for accurate diagnosis and treatment. This demonstrated effective improvement in the conscious erectile status and erectile function scores of patients suffering from ED.