Long-term tadalafil once daily in Chinese men with erectile dysfunction: a 2-year final analysis of a post-marketing, multicenter, randomized, open-label trial.

The long-term safety and effectiveness of once-daily tadalafil is crucial, but limited data are available in Chinese patients with erectile dysfunction (ED). In this post-marketing, multicenter, randomized, open-label trial with 2-year follow-up, 635 ED cases were randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months, of whom 580 continued once-daily tadalafil 5 mg for 21 months. Treatment-emergent adverse events in the 12-month and 24-month period were similar, with the most common being viral upper respiratory tract infection, upper respiratory tract infection, and headache. Significant improvement from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) score was detected at month 12 (least squares mean [LSM] change: 7.9, 95% confidence interval [CI]: 7.5-8.4, P < 0.001) and was maintained to month 24 (LSM change: 8.6, 95% CI: 8.1-9.0, P < 0.001). The proportions of patients regaining normal erectile function (IIEF-EF score ≥26) were 43.7% and 48.0% at months 12 and 24, respectively. Global Assessment Questionnaire results showed improved erection function in 97.5% of patients and improved ability to engage in sexual activity in 95.9% of patients at month 12; these values were 96.1% and 95.0% at month 24, respectively. The quality of sexual life score based on the Sexual Life Quality Questionnaire (SLQQ) was increased by 52.2% at month 12 and by 55.3% at month 24 (both P < 0.001). The treatment satisfaction score determined by SLQQ (mean ± standard deviation) was 62.4 ± 21.0 at month 12 versus 65.9 ± 20.2 at month 24. Two-year daily application of tadalafil 5 mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

Efficacy and Safety of Avanafil in Chinese Subjects With Erectile Dysfunction: A Multi-Center, Randomized, Double-Blinded, Placebo-Controlled Phase III Clinical Trial.

INTRODUCTION: The incidence of erectile dysfunction (ED) increases with age in mainland China and phosphodiesterase 5 inhibitors (PDE5i) are the major drugs used for its treatment. AIM: To determine the efficacy and safety of Chinese developed avanafil as therapy for ED in China. METHODS: This phase III trial was carried out in 7 medical centers in China. Eligible subjects suffering from ED were allocated randomly into 3 groups (ratio 1:1:1) and orally received a placebo, 100 or 200 mg avanafil for a total of 12 weeks. MAIN OUTCOME MEASURES: The primary endpoint was changes in erectile function (EF) domain scores according to the International Index of EF (IIEF) questionnaire from baseline to week 12 of therapy. Secondary endpoints assessments were changes in the response rates of SEP, Q2 and Q3; changes in IIEF other domain scores. Safety evaluation monitored treatment-emergent adverse events (TEAEs), serious TEAEs, laboratory test results, vital signs and electrocardiographs. RESULTS: Of 218 randomized ED subjects, 182 (83.5%) completed the study. After 12-week therapy, alterations from baseline of the mean IIEF-EF domain scores in the 100 mg and 200 mg groups were greater than for the placebo (all P < .05) group. The changes in mean SEP Q2 response rates from baseline to week 12 in the placebo, 100 mg and 200 mg groups were 5.4%, 22.3% and 22.1%, and SEP Q3 response rate were 22.7%, 42.6% and 38.1%, respectively. Avanafil treatment (regardless of dose) improved EF vs placebo for most of other secondary efficacy endpoints studied (all P < .05). No differences were detected in efficacy endpoints between the 100 and 200 mg dosage groups (all P > .05) or in the incidence of TEAEs and drug-related TEAEs among the 3 groups (all P > .05). CONCLUSION: Avanafil (100 or 200 mg) was effective and generally well tolerated in Chinese subjects with ED. Jiang H, Lin H, Li F, et al. Efficacy and Safety of Avanafil in Chinese Subjects With Erectile Dysfunction: A Multi-Center, Randomized, Double-Blinded, Placebo-Controlled Phase III Clinical Trial. Sex Med 2021;9:100337.

[Priligy combined with behavioral therapy and psychological counseling for primary premature ejaculation].

OBJECTIVE: To observe the clinical effect of priligy (dapoxetine hydrochloride) combined with behavioral therapy and psychological counseling in the treatment of primary premature ejaculation (PPE). METHODS: A total of 202 PPE patients diagnosed from 2017 to 2018 were randomized into a control (n = 100) and an experimental group (n = 102), the former treated with oral priligy at 30 mg 1－3 hours before anticipated sexual activity, and the latter by the same medication combined with 30-minute behavioral therapy and psychological counseling once a month for two times. The therapeutic effects were evaluated according to the Premature Ejaculation Profile (PEP) scores of the patients at 1 and 2 months of treatment. RESULTS: After 1 month of treatment, both groups of the patients showed significant improvement, as compared with the baseline, in the PEP scores on personal distress related to ejaculation (P < 0 05), interpersonal difficulty related to ejaculation (P < 0.05) and satisfaction with sexual intercourse (P < 0.05) but not on perceived control over ejaculation (P > 0.05). At 2 months, however, the patients' scores on all the four PEP items were dramatically improved, even more significantly in the experimental than in the control group, as on perceived control over ejaculation (2.73 ± 0.95 vs 2.22 ± 0.68, P < 0.05), personal distress related to ejaculation (2.97 ± 1.07 vs 2.57 ± 0.69, P < 0.05), interpersonal difficulty related to ejaculation (3.19 ± 1.03 vs 2.77 ± 0.69, P < 0 05) and satisfaction with sexual intercourse (2.85 ± 0.99 vs 2.35 ± 0.63, P < 0.05). There was no statistically significant difference in the incidence rate of adverse events between the experimental and control groups (21.6% vs 20.0%, P > 0.05), and all the symptoms were relieved within 24 hours. CONCLUSIONS: Priligy combined with behavioral therapy and psychological counseling is more effective than priligy alone in improving the sexual function of PPE patients, raise their interest in sexual life and increase the intimacy between the partners, and can even achieve clinical cure in some patients.

Benign testicular cavernous hemangioma presenting with acute onset: A case report.

Cavernous hemangioma is a congenital, benign vascular tumor that occurs in the deep dermis and subcutaneous tissue. Testicular cavernous hemangioma is extremely rare, mostly occurring during childhood or adolescence. Testicular cavernous hemangioma is a benign tumor that appears as a slowly growing painless mass. In rare cases, it may be associated with acute testicular infarction or torsion with acute onset. We herein report the case of a patient with an atypical presentation of testicular cavernous hemangioma, characterized by acute painful testicular enlargement triggered by minor injury. The patient underwent right radical orchiectomy, and histopathological examination confirmed the diagnosis of testicular cavernous hemangioma. Although this is a rare tumor, it should be considered in the differential diagnosis of testicular tumors.

Clinical features of and couple's attitudes towards premature ejaculation: a multicenter cross-sectional study.

INTRODUCTION: The current study aimed to investigate the clinical features of and couple's attitudes towards premature ejaculation (PE). METHODS: Qualified patients were continuously enrolled from 15 medical centers in different regions of China. Patient data were collected from March 1 2017 to July 31 2017. All men were assessed by the Premature Ejaculation Diagnostic Tool (PEDT) and Intravaginal Ejaculation Latency Time (IELT). Besides, sexual desire, force of ejaculation, and the five-item International Index of Erectile Function (IIEF-5) score were recorded. The couple's attitudes towards PE were evaluated by a self-designed questionnaire. RESULTS: In total, 1033 males diagnosed with PE and their sexual partners and 3176 males without PE were enrolled. The mean PEDT and IELT scores of the patients with PE were 14.38 ± 3.68 and 1.59 ± 0.85, respectively. IIEF-5, sexual desire, and force of ejaculation significantly decreased in patients with PE. Among the 1033 couples, 44.3%, 21.39%, and 33.98% of the couples were seeking PE because of the dissatisfaction of the males, the females or both partners, respectively. In terms of the males who were dissatisfied with PE, 49.51% and 17.86% complained of short IELT and inability to control ejaculation. In terms of the females dissatisfied with PE, 41.61%, 19.93%, 21.68%, and 14.51% complained of arousal difficulty, weak sexual desire, failing to have organism and poor relationship, respectively. CONCLUSIONS: PE has a negative impact on erectile function, sexual desire, and force of ejaculation. Sexual partners play important roles in the medical procedures for addressing PE.

Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction: interim results of a multicenter, randomized, open-label trial.

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

Identification of candidate genes that may contribute to the metastasis of prostate cancer by bioinformatics analysis.

To screen for marker genes associated with to the metastasis of prostate cancer (PCa), in silico analysis of the Gene Expression Omnibus dataset GSE27616, which included 4 metastatic and 5 localized PCa tissue samples, was performed. Differentially expressed genes (DEGs) were identified. Their potential functions were identified by Gene Ontology and Kyoto Encyclopedia of Gene Genomes pathway enrichment analyses. Furthermore, protein-protein interaction (PPI) networks for DEGs were constructed using Cytoscape. Module analysis of the PPI networks was performed with Cluster ONE. A total of 561 DEGs were screened, including 208 upregulated and 353 downregulated genes. Proliferating cell nuclear antigen (PCNA) and cluster of differentiation 4 (CD4) exhibited the highest degrees of connectivity in the PPI networks for up- and down-regulated DEGs, respectively. The DEGs in module A, including CD58, 2, 4 and major histocompatibility complex, class II DP-ß1 were enriched in 'cell adhesion molecules'. Anaphase promoting complex subunit 4, cell division cycle 20 and cell division cycle 16 in module B were primarily enriched in 'cell cycle'. The DEGs, including CD4, PCNA and baculoviral IAP repeat containing 5, may have critical roles in PCa metastasis and could thus be used as novel biomarker candidates for metastatic PCa. However, further studies are required to verify these results.

Comparison of miRNA and gene expression profiles between metastatic and primary prostate cancer.

The present study aimed to identify the regulatory mechanisms associated with the metastasis of prostate cancer (PC). The microRNA (miRNA/miR) microarray dataset GSE21036 and gene transcript dataset GSE21034 were downloaded from the Gene Expression Omnibus database. Following pre-processing, differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) between samples from patients with primary prostate cancer (PPC) and metastatic prostate cancer (MPC) with |log2 fold change (FC)| >1 and a false discovery rate <0.05 were selected using the Linear Models for Microarray and RNA-seq Data 4 package of R. Next, a DEM-DEG regulatory network was constructed by downloading miRNA-DEG pairs from the miRNA.org database. Finally, functional annotation of each DEM-DEG module was performed using the Database for Annotation, Visualization and Integrated Discovery based on the Gene Ontology database. The upregulated miRNAs, including miR-144, miR-494 and miR-181a, exhibited a higher degree of connections compared with other nodes, including in the DEM-DEG regulatory network, and regulated a number of downregulated DEGs. According to the functional annotation of the DEM-DEG modules, miR-144 and its targeted DEGs enriched the highest number of biological process terms (36 terms), followed by miR-494 (24 terms), miR-30d (18 terms), miR-181a (15 terms), hsa-miR-196a (8 terms), miR-708 (7 terms) and miR-486-5p (2 terms). Therefore, these miRNAs may serve roles in the metastasis of PC cells via downregulation of their corresponding target DEGs.

Inhibition of prostate cancer RM1 cell growth in vitro by hydroxyapatite nanoparticle­delivered short hairpin RNAs against Stat3.

The present study investigated the effect of signal transducer and activator of transcription 3 (Stat3) interference on RM1 prostate cancer cell viability in vitro, using plasmid­based Stat3 specific short hairpin RNA (sh­Stat3) delivered by hydroxyapatite nanoparticles (HAP). HAP carrying sh­Stat3 plasmids were transfected into tumor cells. MTT assays were used to measure RM1 cell viability 24 and 48 h following transfection, and the apoptosis rate and cell cycle phase distribution were determined by flow cytometry. Stat3 mRNA expression levels were measured by reverse transcription­quantitative polymerase chain reaction and Stat3, Cyclin D1, B cell lymphoma 2 apoptosis regulator (Bcl­2), vascular endothelial growth factor (VEGF), Bcl­2 associated X apoptosis regulator (Bax) and cleaved­caspase­3 protein expression levels were detected using western blot analysis. The results demonstrated that HAP­delivered sh­Stat3 significantly decreased RM1 cell viability through the promotion of cell cycle arrest and apoptosis. Stat3 mRNA and protein expression levels were significantly downregulated in RM1 cells. Bcl­2, VEGF and Cyclin D1 were also significantly downregulated, but cleaved­caspase­3 and Bax mRNA and protein expression levels were significantly upregulated. HAP­delivered sh­Stat3 decreased RM1 cell viability in vitro, and HAP assisted plasmid­based delivery of shRNA into tumor cells. The present results suggest that HAP may be a useful method for successful shRNA delivery into tumors.

Embryonal rhabdomyosarcoma of the epididymis presenting as epididymitis: A case report.

Paratesticular rhabdomyosarcoma (RMS) is an extremely rare malignancy in adults, accounting for 7% of all RMS cases and 6% of all non-germinal intrascrotal tumors. The clinical signs are similar to those of a hydrocele or testicular tumor, typically presenting as a unilateral, painless mass in the inguinal canal or scrotum. No specific serum markers are currently available for this tumor. RMS of the epididymis is extremely rare. Particularly when it is associated with epididymitis, this malignancy is usually overlooked. We herein present a case of epididymal embryonal RMS, manifesting an painful scrotal edema, misdiagnosed as epididymitis. The patient received 3 cycles of adjuvant chemotherapy postoperatively and remained disease-free after 4 years of follow-up.

[Reliability and validity of the Chinese version of The Premature Ejaculation Diagnostic Tool].

OBJECTIVE: To translate the English version of The Premature Ejaculation Diagnostic Tool (PEDT) into Chinese, evaluate its reliability and validity, and analyze its feasibility in the diagnosis of premature ejaculation (PE). METHODS: Following the forward-backward translation procedure, we developed the Chinese version of PEDT, which was then revised by andrologists and bilingual linguists. We enrolled subjects with or without PE from 15 urological or andrological clinics in China and obtained the information about their demographic characteristics, PEDT scores, and intra-vaginal ejaculation latency time (IELT). We evaluated the internal consistency of PEDT using Cronbach alpha, was examined its reliability and stability by test-retest analysis, analyzed its correlation with IELT by Spearman correlation analysis, and tested its sensitivity and specificity by receiver operating characteristic ( ROC) analysis. RESULTS: Totally, 570 PE patients (aged [30.66 ± 7.11] years) and 226 non-PE men (aged [33.01 ± 5.41] years) were recruited, with the mean IELT of (1.34 ± 0.54) min in the former and (11.09 ± 7.5) min in the latter group. The Cronbach's alpha of the Chinese version of PEDT was 0.79, and the test-retest correlation coefficient was 0.75 (P < 0.01). The PEDT score was negatively correlated with IELT (Spearman's p = -0.52, P < 0.01). When the cutoff value of PE diagnosis was defined as 7.5, the sensitivity and specificity of PEDT were 0.80 and 0.78, and when as 8.5, they were 0.72 and 0.89, respectively. CONCLUSION: The Chinese version of PEDT was demonstrated to have good internal consistency, reliability, and validity, as well as a high predictability for PE. It can be used as a reliable and convenient tool to screen PE among Chinese men.

[Protective effect of lycopene on human spermatozoa during cryopreservation and its mechanism].

OBJECTIVE: To investigate the protective effect of lycopene against cryopreservation injury of post-thawing human sperm and its mechanism. METHODS: Semen samples were collected from 25 volunteers, each sample equally divided into four parts to be cryopreserved with cryoprotectant only (Ly0 control) or cryoprotectant + lycopene at the concentrations of 2 (Ly2), 5 (Ly5), and 10 µmol/L (Ly10), respectively. Before and after thawing, the semen samples were subjected to computer-assisted semen analysis ( CASA) for sperm kinematics, flow cytometry for sperm apoptosis, thiobarbituric acid assay for malondialdehyde (MDA) concentration, and JC-1 fluorescent staining for the sperm mitochondrial membrane potential (MMP). RESULTS: After cryopreservation, sperm motility was markedly decreased in all the groups (P < 0.01). The rate of sperm apoptosis was significantly lower in the Ly5 group than in the Ly0 control ([25.68 ± 4.36]% vs [33.26 ± 4.78]%, P < 0.05), while sperm MMP remarkably higher in the former than in the latter ([66.18 ± 14.23]% vs [55.24 ± 12.31]%, P < 0.05). The Ly2, Ly5 and Ly10 groups showed no statistically significance differences in the MDA level from the Ly0 control (P > 0.05). CONCLUSION: Addition of lycopene at a proper concentration to cryoprotectant may reduce oxidative damage to sperm mitochondria in the freezing-thawing process, attenuate oxidative stress injury induced by reactive oxygen species to sperm plasma membrane, and improve the anti-apoptosis ability of sperm.

Adenomatoid Tumor of the Tunica Albuginea in a Boy: A Case Report and Literature Review.

Adenomatoid tumors (AT) are the most common paratesticular neoplasms and account for approximately 30% of all paratesticular masses. Most of them occur in the third or fourth decade and present as well-defined firm and painless masses. We report here a case of adenomatoid tumor from tunica albuginea. This patient is a 12-year-old boy with left testicular pain for 6 months. Scrotal ultrasonography revealed a solid mass of paratesticular origin. The histology and immunohistochemistry confirmed the final diagnosis. A right tumor resection was performed. Because of its rarity, the clinical and histopathologic appearance is seldom illustrated. Here we present a case report and a comprehensive literature review with the objective of providing useful information on this entity.

[Yimusake Tablet: safe and efficacious for premature ejaculation].

OBJECTIVE: To objectively evaluate the efficacy and safety of Yimusake Tablet in the treatment of premature ejaculation (PE) through a multi-centered large-sample trial. METHODS: We conducted a multi-centered, open, fixed-dose, and self-compared clinical trial among 300 patients with diagnosed PE. The trial lasted 12 weeks, including 4 weeks without any medication and 8 weeks of treatment with Yimusake Tablet, 2 pills (1 g) per night. We observed the intravaginal ejaculation latency time (IELT) before and after treatment, evaluated the safety of medication, and performed a questionnaire investigation on the patients' satisfaction. RESULTS: Of the 300 PE patients, 288 accomplished the clinical trial. The patients ranged in age from 22 to 60 years, averaging at 31.6 years. The mean IELT of the patient was 62.5 seconds at baseline, 168.9 seconds after 4 weeks of treatment with Yimusake Tablet, and 222.2 seconds after 8 weeks of medication. Among the 157 patients with normal erectile function (IIEF >21), the mean IELT was 71.4 seconds before treatment, 147.4 seconds after 4 weeks of medication, and 172.5 seconds after 8 weeks of medication. The patients' satisfaction was significantly increased after treatment. Those complicated by mild to moderate erectile dysfunction achieved different degrees of improvement in the IIEF-5 score, with a mean increase of 3.8. Only a few patients experienced mild adverse events, including constipation, dry mouth, nose bleeding, abdominal pain, and lumbosacral pain, which were all relieved without drug withdrawal. CONCLUSION: Yimusake Tablet is a safe and effective medicine for the treatment of PE.

A rare case of bilateral sequential spermatocytic seminoma.

Spermatocytic seminoma (SS) is a rare testicular neoplasm characterized by a palpable, painless, slowly enlarging mass in the testis. Even more rare is a synchronous bilateral presentation. Only eight cases of bilateral SS have been reported in the literature, of which three cases were present with synchronous testis enlargement, and five were sequential. Here, we report an additional case of synchronous bilateral SS and present a comprehensive relevant literature review concerning clinical features, histopathology, and treatment.

Liposarcoma of the spermatic cord mimicking a left inguinal hernia: a case report and literature review.

Liposarcoma of the spermatic cord (LSC) is a rare condition characterized by a painless inguinal or scrotal mass. To our knowledge, only about 200 cases have been previously reported in the literature. These tumors are often mistaken for common scrotal swellings, such as hydroceles and hernias. We present a LSC case in which a definitive diagnosis was obtained upon histological examination. We also provide a literature review of other cases that have been reported.

[Expressions of differential proteins in the expressed prostatic secretion of patients with III A chronic prostatitis].

OBJECTIVE: To study the expressions of differential proteins in the expressed prostatic secretion (EPS) of patients with III A chronic prostatitis and healthy men. METHODS: We collected EPS samples from 35 patients with III A chronic prostatitis and 18 age-matched healthy men, and detected the differentially expressed proteins in EPS by MALDI-TOF/MS. Based on the data obtained, we conducted a statistical analysis on the mass-to-charge (m/z) ratios of different proteins and a retrieval analysis on the relevant proteins using the protein database. RESULTS: In the comparative studies of the III A chronic prostatitis patients and healthy men, 5 proteins were detected as at least 2-fold differentially expressed, which were probably brevinin-2Eg, big endothelin-1, alpha-defensin 15, beta-defensin 134 and prostatic steroid-binding protein C2. The m/z ratios were significantly up-regulated in 3 372, 3 487, 425 and 5 325 Da proteins (P < 0.01) and down-regulated in 10631Da (P < 0.01). CONCLUSION: Proteins are differentially expressed in the EPS of III A chronic prostatitis patients and healthy men, and these proteins may be significantly correlated with the development and progression of III A chronic prostatitis.

Aphallia in an adult male with 46, XY karyotype.

Aphallia is a rare urogenital anomaly with an estimated incidence of 1 in 10-30 million. We report a case of aphallia in a male, who had two well-developed testicles, but lacked a penis. Digital rectal examination revealed the urethral meatus was opening to the anterior wall of the rectum posterior to the sphincter. Magnetic resonance imaging showed complete absence of penile development with normal testis and scrotum, as well as the urethra running posterior to the prostatic apex and corpus spongiosum in sagittal and coronal T2-weighted images. Chromosome karyotype confirmed 46,XY, and the polymerase chain reaction method tested no azoospermic factor (AZF) or sex-determining region Y (SRY) gene deletion. Taking into account the physical and psychosocial conditions, seeking a female without sexual desire as his wife was recommended.

[Clinical analysis of 87 cases of testicular tumor].

OBJECTIVE: To improve the diagnosis and treatment of testicular tumor. METHODS: Eighty-seven cases of testicular tumor were retrospectively studied. RESULTS: Of the total number, 79 cases were pathologically diagnosed as germ cell tumor (90.1%), among which there were 44 cases of seminoma (55.7%) and 7 cases of benign tumor (8.1%). Nonseminoma germ cell tumor (NSGCT) was found mainly among those under 5 and from 18 to 40 years of age, while seminoma chiefly among those beyond 17, and testis tumor was rare among those between 5 and 17 years old (1 case only). Three-year and 5-year survival rates of seminoma and NSGCT were 90.6% and 81.3%, and 83.3% and 56.7%, respectively. CONCLUSION: (1) Testicular tumors are mostly germ cell tumors. (2) NSGCT develops mainly among those under the age of 5 and from 18 to 40. (3) Seminoma is rare in those under 18. (4) Testicular tumor rarely develops among those between 5 and 17 years old. (5)Three-year and 5-year survival rates for seminoma are higher than those for NSGCT.