Comprehensive Perspectives for Erectile Dysfunction Pharmacotherapy: From Mechanism to Application.

In recent years, the incidence of erectile dysfunction (ED) has continued to rise worldwide. Since pharmacotherapy is still the most common and effective method for the treatment of ED at present, many methods and drugs have been designed or developed for the treatment of ED. Oral phosphodiesterase-5 inhibitors and androgen supplement therapy are currently the common therapeutics for ED; however, some patients have poor responses to these drugs because of the multiple pathogenic mechanisms of ED. Researchers are trying to find other treatment ways. On the one hand, many new strategies and concepts, such as targeted therapy, are also integrated into clinical or preclinical research; on the other hand, some combined therapies that have synergistic effects with a reduced dose of a single drug and less adverse effects are also developed. This review article summarized the efficacy of the latest first-line, second-line drugs and adjuvant therapies for the treatment of ED, as well as the application of comprehensive treatments, which will help doctors not only deeply understand the mechanism of ED but select the suitable therapeutics for those patients.

Serum Metabolomic Patterns in Patients With Aldosterone-Producing Adenoma.

Aldosterone-producing adenoma (APA), the main cause of endocrine hypertension, has recently been reported to be associated with other diseases, such as metabolic syndrome, but the detailed mechanism underlying this association remains unclear. Here, we used untargeted metabolomics and compared the abundance of serum metabolites between essential hypertension (EHT) and APA patients, as well as the serum metabolites of APA patients before and after adrenalectomy. Our results revealed 44 differential metabolites between APA and EHT patients and 39 differential metabolites between pre- and postoperative APA patients. Several metabolites involved in cardiovascular disease, obesity, and diabetes were dysregulated in APA patients compared to EHT patients, including arachidonic acid metabolites [e.g., 5(S)-HpETE and 12-HETE], amino acids (e.g., L-carnitine, taurine, and L-arginine), nucleotide metabolites (e.g., hypoxanthine) and cholesterol 3-sulfate. Importantly, the levels of hypoxanthine and cholesterol 3-sulfate, two metabolites that promote the development of atherosclerotic lesions and obesity, were originally increased in APA patients, but those elevated levels were reversed by adrenalectomy. Conversely, levels of L-carnitine and (3-carboxypropyl) trimethylammonium cation, two metabolites participating in lipid metabolism, were decreased in APA patients but increased postoperatively. We conclude that APA might participate in cardiovascular and metabolic diseases by regulating serum metabolites.

Exosome-mediated miR-9-5p promotes proliferation and migration of renal cancer cells both in vitro and in vivo by targeting SOCS4.

Exosomes secreted by cancer cells play important roles in tumor progression by interacting with cell receptors. Renal cancer derived exosomes contain miRNAs which are associated with cell proliferation and invasion. Micro RNA 9-5 (miR-9-5) is highly expressed in the serum of renal cancer patients with advanced (tumor size - node - metastasis) TNM stage and Fuhrman grade. miR-9-5p is extensively expressed in exosomes derived from renal cancer cells. Overexpression of miR-9-5p promotes proliferation and invasion of A-704 (a cancer cell line of human kidney) cells via targeting and deregulating SOCS4 mRNA. Inhibition of the Janus kinase (JAK)/signaling transducer and activator of transcription (STAT) pathway by SOCS4 will be reduced, which leads to phosphorylation of STAT3 and JAK. Activated cytokine signaling promotes cell proliferation and invasion, and inhibits apoptosis. Moreover, overexpression of SOCS4 reduces miR-9-5p levels and plays an opposite role in cell. To conclude, exosomal miR-9-5p plays important roles in renal cancer both in vivo and in vitro, indicating it may be used as biomarker for diagnosis and for monitoring the efficacy if therapy.

The Retroperitoneal Laparoscopic Renal Capsulectomy for Spontaneous Renal Subcapsular Fluid Collection: A Case-Series Report and Literature Review.

Spontaneous renal subcapsular fluid collection may occur as a rare presentation of nephritic syndrome, and distension of the renal capsula and Gerota fascia due to massive fluid accumulation may cause pain. In addition, hypertension secondary to renal ischemia and activation of renin-angiotensin-aldosterone system may also occur. The objective of this study is to evaluate the surgical outcome of retroperitoneal laparoscopic renal capsulectomy for patients with this disease.We retrospectively analyzed the clinical data of 10 female patients with spontaneous renal subcapsular fluid collection, diagnosed with B ultrasound and enhanced computed tomography (CT) scan. Eight patients first underwent percutaneous renal subcapsular drainage, which seemed to be less effective, and then all patients underwent retroperitoneal laparoscopic renal capsulectomy. The volume of renal subcapsular fluid was documented, the fluid was examined by routine biochemical tests, and the excised renal capsules underwent pathological examination individually. The postoperative drainage time for each patient was documented, and follow-up was conducted 1, 3, 6, 12 months, and 2 years postoperatively.Retroperitoneal laparoscopic renal capsulectomy was successfully performed in all patients with no major complications. The average volume of renal subcapsular fluid was 436 milliliter (mL, 180-880 mL) in light yellow color, and the concentration of creatinine and urea nitrogen was quite similar to that of serum. The pathological findings revealed fibrous dysplasia of the renal capsule with chronic infiltration of inflammatory cells. The average drainage time was 11.5 days (5-30 days) postoperatively. All patients recovered 1 month after the operation and there were no recurrences with a mean follow-up period of 12 months (6-24 months).The reason for spontaneous renal subcapsular fluid collection is unknown, and the aim of treatment is mainly to alleviate symptoms. In our experience, retroperitoneal laparoscopic renal capsulectomy is an effective surgical treatment, especially for patients who were refractory to percutaneous renal subcapsular drainage, with no observed recurrence.

[Efficacy and tolerability of dapoxetine in the treatment of premature ejaculation].

OBJECTIVE: To investigate the efficacy and adverse effects of dapoxetine in the treatment of premature ejaculation. METHODS: We randomly assigned outpatients with premature ejaculation in the proportion of 2:1 to receive 30 mg dapoxetine on demand (n =78) or 50 mg sertraline qd for one month (n = 39). Follow-up was accomplished in 95 cases, 63 in the dapoxetine group and 32 in the sertraline group. We recorded the intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, and adverse reactions of the patients and compared them between the two groups. RESULTS: IELT was significantly increased in both the dapoxetine (from [0.87 ± 0.31] to [2.84 ± 0.68] min, P < 0.05) and the sertraline group (from [0.84 ± 0.28] to [2.71 ± 0.92] min, P < 0.05) after medication. Based on the CGIC scores in premature ejaculation, the rate of excellence or effectiveness was 36.5% in the dapoxetine and 37. 5% in the sertraline group, and the rate of improvement was 63.5% in the former and 71.9% in the latter. The incidence rates of dizziness, nausea, headache, and diarrhea were slightly higher (P > 0.05) while those of fatigue, somnolence, and dry mouth significantly higher (P < 0.05) in the sertraline than in the dapoxetine group. CONCLUSION: On-demand oral medication of dapoxetine is effective and well-tolerated for the treatment of premature ejaculation.

[Survey of the prevalence of chronic prostatitis in men with premature ejaculation].

OBJECTIVE: To investigate the prevalence of chronic prostatitis in men with premature ejaculation. METHODS: The segmented urine specimens before and after prostatic massage and the expressed prostatic secretion specimens from 106 patients with premature ejaculation and 38 controls were evaluated by microscopic and/or bacteriological studies. The prevalence of premature ejaculation was also investigated in 120 patients with chronic prostatitis. RESULTS: Prostatic inflammation was found in 46.2% and chronic bacterial prostatitis in 34.7% of the subjects with premature ejaculation, respectively. Compared with the controls, the findings were statistically significant (P < 0.05). The prevalence of premature ejaculation in the patients with chronic prostatitis was 47.5% (57/120). CONCLUSIONS: Chronic prostatic inflammation may play a role in the pathogenesis of some cases of premature ejaculation and it is important to give a careful examination of the prostate before initiating any therapy for premature ejaculation.