CD133 antibody targeted delivery of gold nanostars loading IR820 and docetaxel for multimodal imaging and near-infrared photodynamic/photothermal/chemotherapy against castration resistant prostate cancer.

Due to the lack of effective strategies on the treatment of castration resistant prostate cancer (CRPC), we established a multifunctional nanoplatform (GNS@IR820/DTX-CD133) for the synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemotherapy (CT) under the monitoring of multimodal near-infrared (NIR) fluorescence/photoacoustic (PA) imaging. Benefiting from the guided effect of CD133 antibody, GNS@IR820/DTX-CD133 can targetedly deliver the loaded drug to the tumor tissues, which can further contribute to the combined therapeutic effect. Our experimental results prove that the bio-distribution of GNS@IR820/DTX-CD133 can be monitored with NIR fluorescence and PA imaging. In addition, the application of GNS@IR820/DTX-CD133 for in vitro and in vivo therapy achieves the excellent antitumor effects of the synergistic PTT/PDT/CT strategies under the NIR-light irradiation. Therefore, as a multifunctional nanoplatform integrating the PTT/PDT/CT strategies with tumor multimodal imaging or drug tracing, GNS@IR820/DTX-CD133 has the great potential for clinical applications in the antitumor therapy of CRPC.

Staged male genital reconstruction with a local flap and free oral graft: a case report and literature review.

BACKGROUND: Male genital skin loss is a common disease in urology. However, male genital skin loss accompanying a penile urethra defect is rarely reported. Herein, we describe a novel surgical technique using a composite local flap and oral mucosal graft to reconstruct the penis, which may provide a new solution for patients with similar conditions. CASE PRESENTATION: A 36-year-old male with a penile urethra defect and a large area of genital skin loss required urethral reconstruction. The meatus had descended to the penoscrotal junction. This procedure was divided into three stages. The first stage of the surgery involved burying the nude penile shaft beneath the skin of the left anteromedial thigh for coverage of the skin defect. The second stage consisted of releasing the penis and expanding the size of the urethral plate for further urethroplasty. The third stage consisted of reconstruction of the anterior urethra 6 months later. Postoperatively, the patient reported satisfactory voiding. The maximal flow rate (MFR) was 22.2 ml/s with no postvoiding residual urine at the 24-month follow-up visit. No edema, infection, hemorrhage, or cicatricial retraction were observed. The patient's erectile function was satisfactory, and his international index of erectile function-5 score (IIEF-5 score) was 23 at the 24-month follow-up visit. Additionally, the presence of nocturnal penile tumescence demonstrated that he had normal erectile function. CONCLUSIONS: This procedure is an effective surgical option for men with complete foreskin and penile urethra defects. It could also be extended as a treatment strategy when composite local or pedicle transposition flaps and free grafts are needed for specific patients.

[comIdiopathic scrotal calcinosis: A report of 10 cases and review of the literature].

OBJECTIVE: To investigate the clinical features, pathogenesis, diagnosis and scrotal reconstruction in the treatment of idiopathic scrotal calcinosis (ISC). METHODS: From March 2007 to October 2018, 10 ISC patients, aged 28－79 (mean 45) years and with a disease course of 6－497 (mean 128.4) months, were treated in our hospital. We retrospectively analyzed their clinical data and reviewed related literature. RESULTS: All the patients underwent physical examination and biochemical and parathyroid function tests. None of them had a history of endocrine or metabolic disease, or trauma, or a family member with similar diseases, and none had subjective symptoms except local pruritus in 1 case. All were treated surgically and post-operative follow-up revealed no recurrence. Histopathological examination of the excised lesion confirmed it to be ISC. CONCLUSIONS: ISC is a rare localized benign disease, of which surgery seems an effective option for the definite diagnosis and treatment. Occasionally scrotal reconstruction may be required in case of extensive involvement of the scrotal skin.

Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites.

BACKGROUND: Extramammary Paget disease (EMPD) is a rare malignant dermatosis with poorly defined outcomes. We investigated clinical characteristics of invasive EMPD at different anatomic sites and by subject demographics to determine prognostic factors for overall survival (OS). METHODS: All patient data were collected from the Surveillance, Epidemiology, and End Results (SEER) program, 1973-2013, of the U.S. National Cancer Institute. Patients with invasive EMPD of skin, vulva/labia, vagina, scrotum/penis, or other sites were included. After excluding patients with unknown radiation status, data of 2001 patients were analyzed. Primary endpoint was EMPD mortality by anatomic sites. Independent variables included patients' demographic data, concurrent malignancy (ie, non-EMPD related cancers), tumor size, distant metastasis, and surgery and/or radiation or not. RESULTS: Multivariate regression analysis showed that mortality was significantly higher in patients with vaginal EMPD than in patients with vulvar/labial EMPD (adjusted hazard ratio [aHR] = 3.26, p < 0.001). Patients with distant metastasis had higher mortality than those without (aHR = 3.36, p < 0.001). Patients who received surgery had significantly lower mortality than those who did not receive surgery (aHR = 0.77, p = 0.030), and those treated with radiation had significantly higher mortality than those who did not receive radiation (aHR = 1.60, p = 0.002). Older age was associated with significantly increased mortality (aHR = 1.09, p < 0.001), and mortality was significantly higher in males than in females (aHR = 1.42, p = 0.008). CONCLUSIONS: In conclusion, among EMPD patients, mortality is higher in patients with vaginal EMPD than in those with vulvar/labial EMPD and higher in those who are older, those with concurrent malignancy or distant metastasis. Mortality is also higher in males than in females. Surgery is a protective factor and radiation is a risk factor for OS. Greater understanding of EMPD clinical characteristics, and considering EMPD in differential diagnosis of chronic genital and perianal dermatoses may provide support for early EMPD diagnosis and definitive surgical treatment.

[Selective embolization for arterial priapism: A report of 5 cases].

OBJECTIVE: To introduce our experience in the treatment of arterial priapism by superselective embolization. METHODS: This study included 5 cases of perineal trauma-induced arterial erectile dysfunction treated in our departmentbetween February 2011 and May 2015, all failingpreviously to respond to 3 weeks of conservative treatment. The patients were aged 25－47 (mean 35) years, with the onset of arterial priapism at 2－5 days after trauma, and all subjected to physical examination, blood gas analysis, color Doppler ultrasonography of the corpora cavernosum, and IIEF-5 scoring. All the patients underwent superselective embolization, followed by local pressing and cold compression, and IIEF-5 scores were obtained again at 6 and 12 months postoperatively. RESULTS: All the patients had normal erectile functionbefore trauma, with a mean IIEF-5 scoreof 24.60 ± 0.55. Complete detumescenceor painless flaccidity of the penis was achieved in 1 case immediately after surgery and in the other 4 after 3－17 days of postoperative conservative treatment. None of the patients needed a second embolization and no relapse was found during a mean follow-upof 27.2 (13－48)months. The IIEF-5 scores obtained at 6 (24.00 ± 1.02) and 12 months (24.20 ± 0.82) were normal, with no statistically significant differencesfrom that before trauma. CONCLUSIONS: Selective embolization is a safe and effective option for the treatment of arterial priapism. In case of no immediate painless flaccidity of the penis after surgery, conservative treatment can be extended rather than a second operation.

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats.

BACKGROUND/AIMS: Transforming growth factor-ß1 (TGF-ß1) plays important roles in penile corporal fibrosis and veno-occlusive dysfunction (CVOD). Angiotensin II (Ang II) is critically involved in erectile dysfunction, and blocking of Ang II is more important than inhibition of TGF-ß in non-penile tissue fibrosis. However, the role of Ang II in corporal fbrosis and CVOD in a diabetic condition has not been investigated. METHODS: Diabetic rats were treated with sildenafil or losartan (an Ang II antagonist) alone or in combination. Intracavernosal pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were examined. RESULTS: Diabetic rats exhibited decreases in erectile response, severe CVOD, apoptosis, fibrosis, and activation of the TGF-ß1 pathway. Treatment with sildenafil had a modest effect on erectile response and an insignificant suppressive effect on CVOD, apoptosis, fibrosis, and the TGF-ß1 pathway. Although losartan greatly improved the histological and molecular changes and CVOD as compared with sildenafil, its effect on erectile response was low. The combination of sildenafil and losartan had superior effects on these parameters than did either compound alone. CONCLUSION: Ang II activation may be involved in apoptosis and fibrosis of the corpus cavernosum through Smad and non-Smad pathways, resulting in CVOD and ED. The low efficacy of sildenafil in a diabetic ED rat model was at least partly due to its inadequate effects on apoptosis, fibrosis, and CVOD.

Poly r(C) binding protein-1 is central to maintenance of cancer stem cells in prostate cancer cells.

AIMS: To investigate global proteomic changes induced in CD44+CD24- stem cells isolated from the prostate cancer cell lines, LNCaP and DU145, post prolonged TGF-ß treatment in order to understand underlying mechanisms that promote stemness in prostate cancer cells. METHODS: CD44+CD133+α2ß1Integrin+CD24- population was isolated from mock or TGF-ß treated (7 days) prostate cancer cell line, LNCaP, through fluorescent activated cell sorting. Cell lysates were obtained from the ±TGF-ß cell population and proteomics profiling (MS/MS) was performed by mass spectrometry. Relative enrichment or depletion in the CD44+CD24-population post-TGF-ß treatment was determined relative to mock-treated CD44+CD24- cells post normalization to GAPDH expression levels. RESULTS obtained from MS/MS were validated using immunoblotting. Functional validation of one putative regulator was performed using gain-of-function strategy to investigate its role in rendering stemness in LNCaP and DU145 cells in vitro and in promoting tumorigenicity in vivo. RESULTS: TGF-ß treatment caused significant enrichment of CD44+CD24- population in LNCaP cells (22.35 ± 0.94% in mock treated vs 95.23 ± 2.34% in TGF-ß treated cells; P < 0.01), which were also positive for CD133 and α2ß1Integrin. Mass spectrometry analysis of the enriched cell population revealed that sixty-three proteins were either up- or down-regulated greater than five folds, out of which the poly r(C) binding protein (PCBP)-1 was the most down-regulated (9.31 ± 0.05 folds). Ectopic overexpression of PCBP1 in LNCaP and DU145 cells not only attenuated enrichment of CD44+CD133+CD24- population in these cells following TGF-ß treatment, but also significantly decreased tumorigenicity of the stem cell subset, as assessed by in vitro soft agar colony formation and in vivo xenograft assays. CONCLUSION: Our proteomic profiling and subsequent validation indicate that PCBP1 is central to CSCs enrichment and functionality in prostate cancer.

[Surgical repair and reconstruction of male external genitals].

One of the challenges in andrology nowadays is the diagnosis and treatment of external genital abnormalities and defects along with the consequent voiding, sexual, and reproductive dysfunctions, for which no guidelines are yet available. Hitherto, surgical repair and reconstruction are efficient for these diseases. The key to these operations is to individualize surgical strategies according to the specific local lesion and dysfunction, usually involving flap and graft techniques. This article presents our experience in the surgical treatment of penile and scrotal abnormalities and defects with urological and andrological techniques and microsurgical strategies, focusing on the external repair and functional reconstruction. Satisfactory treatment outcomes pivot on a precise evaluation of the disease, a rational design of surgical procedures, and an earnest communication with the patient. Some cases are rather complicated and challenging, usually with complications, and therefore deserve further researches for more effective treatment strategies in clinical practice.

A prospective, randomized clinical trial comparing plasmakinetic resection of the prostate with holmium laser enucleation of the prostate based on a 2-year followup.

PURPOSE: We compared plasmakinetic resection with holmium laser enucleation of the prostate for the treatment of benign prostatic hyperplasia by analyzing 2-year followup data from a prospective randomized clinical trial. MATERIALS AND METHODS: A total of 280 patients were randomly treated with plasmakinetic resection or holmium laser enucleation of the prostate. Perioperative and postoperative outcome data were obtained during a 2-year followup. RESULTS: No significant differences between the 2 surgical groups were observed in the preoperative data. Both groups displayed significant improvements after surgery. However, we identified no significant differences between the 2 groups in the 2-year followup data for I-PSS (International Prostate Symptom Score), quality of life scores or maximum flow rate values. Patients in the holmium laser enucleation group displayed a lower risk of hemorrhage, shorter bladder irrigation and catheter times, and shorter hospital stays. A larger amount of prostate tissue was retrieved in the holmium laser enucleation group, but the operation time was longer for this group than for the plasmakinetic resection group. CONCLUSIONS: Plasmakinetic resection and holmium laser enucleation of the prostate are effective and safe treatments for benign prostatic hyperplasia. Holmium laser enucleation of the prostate can be applied to prostates of all sizes, and involves less risk of hemorrhage, decreased bladder irrigation and catheter times, as well as reduced hospital stay. Thus, we believe holmium laser enucleation of the prostate should be proposed as a potential new gold standard surgical therapy instead of transurethral resection of the prostate for patients with benign prostatic hyperplasia.

A comparative study of the use of a transverse preputial island flap (the Duckett technique) to treat primary and secondary hypospadias in older Chinese patients with severe chordee.

OBJECTIVE: To investigate the outcome between the primary and secondary hypospadias with severe chordee in older patients by the transverse preputial island flap (TPIF). MATERIALS AND METHODS: We retrospectively analyzed 53 hypospadias patients who were performed with TPIF for urethroplasty, including 25 primary hypospadias (Group 1) and 28 secondary hypospadias (Group 2). The mean age in Group 1 was 12.12 ± 10.709 and 18.64 ± 8.727 in Group 2 (P = 0.0181). The mean follow-up time was 38.7 months (22-60 months). RESULTS: All of the foreskin flaps survived after the operation without necrosis. The overall complication rate was 24 % in Group 1 and 53.57 % in Group 2 (P = 0.0280). All the patients were also divided into two cohorts according to their ages in surgery. In the 0-10-yr cohort, there was a significant difference in the overall complication rate between the primary and secondary groups (P = 0.0173). But in the cases who were over 11 year old, there was no significant difference in the overall complications between two groups (P = 0.1603). Also no significant difference was found in the mean length of the urethral defect between two groups (P = 0.8312). CONCLUSION: The Duckett technique is an optional choice for some older Chinese patients undergoing primary operations, but it has a higher complication rate in those who have undergone previous failed urethroplasties. The unsatisfactory results found in the reoperative group were supposed to be linked to the older age, the lack of subcutaneous flap coverage and local scar tissue, but not to the length of the urethral defect.

A comparative study of two single-stage oral mucosal substitution urethroplasty (Kulkarni and Asopa) in the surgical treatments of lichen sclerosus urethral strictures.

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.

Transcorporal Artificial Urinary Sphincter Cuff Placement in a Case Requiring Revision for Urethral Atrophy.

Artificial urethral sphincter (AUS) implantation is the definitive management of male stress urinary incontinence (SUI). Under the long-term pressure of the cuff, recurrence of incontinence caused by urethral atrophy can always be observed in patients. In this situation, distal cuff locations are needed, and new cuff sites should be sought in patients who need to undergo AUS reimplantations. Meanwhile, the circumference of the more distal urethra is often too small to fit with a 4.0 cm cuff. This means that the bulk of the urethra should be added not only for a sufficient urethral circumference but also for better protection. Here, we report a case that required AUS reimplantation because of urethral atrophy. This 73-year-old man had undergone AUS implantation 7 years ago and developed incontinence in the past 3 months. Physical examination and ultrasonography determined that the device still worked, and no obstruction or injury was observed through cystoscopy. Surgery for revision of the AUS was needed. In this operation, a new cuff was implanted transcorporally, which was 2 to 3 cm distal to the original cuff site. During a 6 month short-term follow-up, no stress incontinence, urethral injury, or dysuria was observed. The transcorporal technique offers significant advantages in patients with urethral atrophy: corporal tunica albuginea is added to the urethra, allowing a suitable cuff size and lower risk of erosion. It is worth recommending in the reoperation of AUS implantation.

A Modified Bilateral Scrotal Flap for Penile Skin Defect Repair.

Skin shortages and scar contractures are common complications following penile trauma and tumor surgery, resulting in significant pain and erectile dysfunction. Currently, skin grafts and scrotal flaps are widely used to reconstruct skin shortages. However, various limitations still exist; for instance, the skin graft may cause severe scarring in patients, and the traditional scrotal flap usually requires a two-stage procedure due to the large skin defect. To treat the shortage of foreskin, a modified bilateral scrotal pedicled flap is used. In this procedure, flaps located on each side of the midline of the scrotum, which was pedicled from the anterior scrotal artery, are harvested. Subsequently, these bilateral scrotal flaps, like a butterfly, can successfully cover the foreskin defect. In this study, seven patients underwent this procedure, and satisfactory outcomes were obtained. Only two patients developed necrosis in some small areas of the flaps, which were recovered after wound care. Postoperative penile length significantly increased compared to the preoperative status in both flaccid and erectile states. We believe that modified bilateral scrotal flaps are a simple and effective solution to penile skin shortages and scar contractures.

Three new experimental models of anterior urethral stricture in rabbits.

Background: This study describes and compares three surgical procedures for the construction of urethral stricture (US) models in rabbits. Methods: Forty adult male rabbits were allocated to four groups: 36 rabbits were randomly assigned to three experimental groups, while the remaining 4 were assigned to a sham group. The penis was separated from the rectum. Then along the ventral midline, a longitudinal penile skin incision was made while ensuring that the urethral mucosa was intact and the muscular layer was not completely incised. In group 1 (n=12), ventral semi-circumferential mucosa electrocoagulation of a 1-cm length of the anterior urethra was performed until ulceration occurred. In group 2 (n=12), the ventral urethral mucosa was incised, and electrocoagulation of the dorsal semi-circumferential mucosa was performed. In group 3 (n=12), whole-circumferential mucosa electrocoagulation was performed. In group 4 (n=4), no special treatment was performed. Four weeks later, urethrography, urethroscopy, and histological evaluation were carried out. Results: The weights of the rabbits in the four groups were comparable. There was no significant difference between groups 2 and 3 with regard to operative time, but the operative time in these groups was significantly longer than that in group 1 (group 2 vs. group 1: P<0.05, group 3 vs. group 1: P<0.001). After the surgery, urinary fistula with infection occurred in one rabbit in group 1, and one rabbit died due to urethral atresia in group 3. According to the urethrography and urethroscopy findings, 9 out of 12 rabbits in group 1, 5 out of 12 rabbits in group 2, and 11 out of 11 rabbits in group 3 developed US, while no rabbits in the sham group developed US. Histopathological examination revealed injury to the urothelium, inflammatory infiltration, a decrease in the amount of blood vessels and smooth muscle fibers, and a decrease in the amount of collagen fibers. Conclusions: Compared with the semi-circumferential procedures, the whole-circumferential procedure had a higher success rate. Therefore, this procedure seems to have potential for the construction of long-segment rabbit US models.

Effects of plication procedures in special cases of Peyronie's disease: a single-center retrospective study of 72 patients.

General recommendations regarding surgical techniques are not always appropriate for all Peyronie's disease (PD) patients. Therefore, the purpose of this study was to investigate the effects of plication procedures in PD patients with severe penile curvature and the effects of early surgical correction in patients who no longer have progressive deformities. The clinical data from 72 patients who underwent plication procedures were analyzed in this study. Patients were divided into Groups A and B according to the curvature severity (≤60° or >60°) and Groups 1 and 2 according to the duration of disease stabilization (≥3 months or <3 months). At the 1-year follow-up, 90.0% (36/40) and 90.6% (29/32) patients reported complete penile straightening, and 60.0% (24/40) and 100.0% (32/32) patients reported penile shortening in Groups A and B, respectively. No curvature recurrence occurred in any patient, and no significant differences were observed in postoperative International Index of Erectile Function-Erectile Function domain (IIEF-EF), erectile pain, sensitivity, or suture knots on the penis whether such outcomes were grouped according to the curvature severity or the duration of stabilization. However, the duration from symptom onset to surgical management in Group 1 was significantly longer than that in Group 2 (mean ± standard deviation [s.d.]: 20.9 ± 2.0 months and 14.3 ± 1.2 months, respectively, P < 0.001). The present study showed that the plication procedures seemed to be an effective choice for the surgical treatment of PD patients with severe penile curvature. In addition, the early surgical treatment seemed to benefit those patients who already had no erectile pain and no longer exhibited progressive deformity.

Tumor microenvironment pH-responsive pentagonal gold prism-based nanoplatform for multimodal imaging and combined therapy of castration-resistant prostate cancer.

Given that there is lack of effective therapies for castration-resistant prostate cancer (CRPC), the combination of photothermal (PTT), photodynamic (PDT), and chemical therapy (CT) has emerged as a prominent strategy. Tumor-targeted delivery and controlled release of antitumor drug are key-elements of any combined therapy. Considering these important elements, we designed and constructed tumor microenvironment (TME)-activated nanoprobes (PGP/CaCO3@IR820/DTX-HA). The CaCO3 shell could efficiently entrap the photosensitizer IR820 and the chemotherapeutic docetaxel (DTX) on the surface of pentagonal gold prisms (PGPs) to prevent elimination from the circulation, and it could act as a TME-trigger to achieve TME-responsive drug release. After modification with hyaluronic acid, PGP/CaCO3@IR820/DTX-HA was capable of synergistic TME-triggered PTT/PDT/CT and tumor-targeted delivery. Our in vitro and in vivo studies demonstrate that PGP/CaCO3@IR820/DTX-HA could achieve synergistic antitumor effects following near-infrared (NIR)-light irradiation. In addition, using the NIR fluorescence signal from IR820 and the photoacoustic (PA) signal from PGPs, i.e., through multimodal fluorescence/photoacoustic imaging, we could monitor the in vivo distribution and excretion of PGP/CaCO3@IR820/DTX-HA. Therefore, it can be concluded that PGP/CaCO3@IR820/DTX-HA shows promising clinical translational potential as a treatment for CRPC. STATEMENT OF SIGNIFICANCE: Utilizing pentagonal gold prisms (PGPs), we constructed a multifunctional nanoplatform (PGP/CaCO3@IR820/DTX-HA) for effectively delivering agents into the tumor microenvironment (TME) for the diagnosis and therapy of castration-resistant prostate cancer (CRPC). The synthetic nanoplatform can satisfy TME-activated synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemical therapy (CT) and NIR fluorescence imaging/photoacoustic (PA) imaging. Hyaluronic acid (HA) on the surface of nanoplatform allowed the specific tumor-targeting capacity and biocompatibility. In conclusion, PGP/CaCO3@IR820/DTX-HA could be a promising integrated nanoplatform for CRPC diagnosis and treatment.

Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models.

BACKGROUND: Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived mesenchymal stem cell (ADSC)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED. METHODS: In this study, ED was induced in Sprague Dawley (SD) rats using chronic intermittent hypoxia (CIH) exposure. CIH-mediated influences were then measured in the corpus cavernous smooth muscle cells (CCSMCs). RESULTS: Our data showed that miR-301a-3p-enriched exosome treatment significantly recovered erectile function in rats and CCSMCs by promoting autophagy and inhibiting apoptosis. The treatment also significantly recovered the level of alpha smooth muscle actin (α-SMA) in rats and CCSMCs. Bioinformatics predicted that phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) might be targets of miR-301a-3p. CONCLUSIONS: Our results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/hypoxia-inducible factor-1 alpha (HIF-1α) and TLR4 signaling pathways play key roles in the progression of ED. The findings in this study suggest that miR-301a-3p should be considered a new therapeutic target for treating ED associated with OSA.

Transcriptome sequencing reveals a lncRNA-mRNA interaction network in extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA-mRNA interaction network in extramammary Paget's disease. METHODS: High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA-mRNA interaction network, which was finally confirmed in vitro. RESULTS: Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA-mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT-PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes. CONCLUSION: These findings suggest that the lncRNA-mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.

Effects of patients' understanding and choice of surgical types on postoperative outcomes of Peyronie's disease: a single-center retrospective study of 108 patients.

Surgical correction can be considered for treating patients with a chronic phase of Peyronie's disease (PD) and persistent penile curvature. In clinical practice, some patients pay too much attention to surgical complications and refuse the recommended feasible surgical types. Meanwhile, they require operations according to their preferences. This study aimed to evaluate the effects of patients' own choice of surgical type on postoperative satisfaction. This retrospective study analyzed data from 108 patients with PD who underwent surgical correction according to doctors' recommendations or patients' own demands. The objective and subjective surgical outcomes were assessed. Patients' understanding of the disease was analyzed using a questionnaire survey. Objective measurements of surgical outcomes, including penile straightening, penile length, and sexual function, in patients who received the recommended surgery, were similar to those in patients who did not accept the recommended surgery. However, subjective evaluations, including erectile pain, discomfort because of nodules on the penis, and decreased sensitivity in the penis, were more obvious in patients who did not follow doctors' recommendations. In addition, a questionnaire survey showed that understanding PD and the purpose of surgery of patients who did not follow doctors' advice were inappropriate, as they did not conform to the principle of treatment. The present study showed that surgical correction seemed to be an objectively effective option in the management of patients in the stable chronic phase of PD. Low patient satisfaction might be related to patients' lack of correct understanding of the disease and its treatment strategy as well as unrealistic expectations.

Treatments of Peyronie's disease with Scutellaria baicalensis and surgery according to the disease course: a single-center retrospective study of 261 patients.

BACKGROUND: Oral medication therapies are more conventional than other non-surgical therapies in the acute phase of Peyronie's disease (PD). Although the commonly used oral drugs for PD have shown poor or indeterminate outcomes, most patients prefer oral medications. The aim of this study was to evaluate the efficacy and safety of Scutellaria baicalensis extract for treating acute-phase PD patients and examine the practicality of treatment strategies for PD according to the disease course. METHODS: This retrospective study was performed at our institution from 2005 to 2015 and analyzed the data of 261 patients with PD. The acute-phase PD patients received Scutellaria baicalensis extract for 6 months. After oral treatment, the patients with persistent curvature underwent surgical correction during the stable phase. RESULTS: During this study period, 183 patients received oral treatment with Scutellaria baicalensis, and 78 patients did not. Compared to the untreated patients, treatment with Scutellaria baicalensis had a significant effect in improving the symptoms of acute-phase PD. The mean time required for stabilization also showed a significant statistical difference. Treatment with Scutellaria baicalensis was safe and well-tolerated. After the disease stabilized, 70 and 31 patients with significant penile curvature underwent surgical correction by 16- dot plication and great saphenous vein grafting procedures, respectively. At the one-year follow-up, complete penile straightening and penile length shortening were observed in 92.86% and 41.43% of the patients after 16-dot plication and in 87.10% and 25.81% of the patients after grafting procedures, respectively. The postoperative Erectile Function domain of the International Index of Erectile Function scales were maintained in all patients after the 16-dot plication procedure and decreased in 54.84% of the patients after the grafting procedure. Overall, 92.86% and 83.87% of the patients who received 16-dot plication and grafting procedures, respectively, were satisfied with the final surgical results. CONCLUSIONS: Treatment with extract of Scutellaria baicalensis seems to be beneficial for improvements in symptoms of acute phase PD and acceleration of the disease stabilization. The 16-dot plication and great saphenous vein grafting procedure seem effective options in the surgical management of the stable phase after Scutellaria baicalensis administration in the acute phase of PD.