BACKGROUND: This study compared the differences of microvesicles (MVs) and microvesicles-delivering Smad7 (Smad7-MVs) on macrophage M1 polarization and fibroblast differentiation in a model of Peyronie\'s disease (PD).
METHODS: Overexpression of Smad7 in rat BMSCs was obtained by pCMV5-Smad7 transfection. MVs were collected from rat BMSCs using ultracentrifugation. In cells, 100 µg/mL of MVs or Smad7-MVs were used to treat the 100 ng/mL of lipopolysaccharide (LPS)-induced RAW264.7 cells or 10 ng/mL of recombinant transforming growth factor-β1 (TGF-β1)-induced fibroblasts. The pro-inflammatory cytokines and markers of M1 macrophages were measured in RAW264.7 cells, and the migration and markers of fibroblast differentiation were measured in fibroblasts. In rats, 50 µg of MVs or Smad7-MVs were used to treat the TGF-β1-induced animals. The pathology of tunica albuginea (TA), the markers of M1 macrophages and fibroblast differentiation in the TA were measured.
RESULTS: The MVs or Smad7-MVs treatment suppressed the LPS-induced macrophage M1 polarization and TGF-β1-induced fibroblast differentiation. Moreover, the Smad7-MVs treatment decreased the fibroblast differentiation compared with the MVs treatment. In the TGF-β1-induced TA of rats, MVs or Smad7-MVs treatment ameliorated the TA fibrosis by suppressing the macrophage M1 polarization and fibroblast differentiation. There was no significance on the M1-polarized macrophages between the MVs treatment and the Smad7-MVs treatment. Meanwhile, the Smad7-MVs treatment had an edge in terms of suppressing the fibroblast differentiation in the TGF-β1-induced PD model compared with the MVs treatment.
CONCLUSIONS: This study demonstrated that Smad7-MVs treatment had advantages over MVs treatment in suppressing of fibroblast differentiation in a model of PD.

BACKGROUND: Peyronie\'s disease (PD) is a common penile disorder characterized by the formation of fibrous noncompliant hard nodules in the tunica albuginea of the penis. Collagenase Clostridium histolyticum (CCH) is an injectable drug that treats PD by enzymatically degrading plaque interstitial collagen. CCH has been used in patients with varying curvature, as well as in the acute and stable phases of the disease, through a variety of treatment regimens and combinations. We carried out a systematic review and meta-analysis to assess the efficacy of CCH combination therapies for PD.
METHODS: We selected 4 observational comparative studies and 3 randomized controlled trials including 532 participants from the PubMed, Embase, and Cochrane databases (until December 2023) to evaluate the efficacy of CCH combination therapies for PD. The primary outcome was clinical efficacy as evaluated by improvement in penile curvature and penile length, as well as by scores on the Peyronie\'s Disease Questionnaire (PDQ) for symptom bother, penile pain, and psychological symptoms. Continuous data were represented by mean difference (MD) and 95% CI. All data were analyzed by Review Manager version 5.3.
RESULTS: For penile length (MD, 0.81 cm; 95% CI, 0.17-1.45; P = .01), PDQ symptom bother (MD, -1.02; 95% CI, -1.83 to -0.21; P = .01), and PDQ penile pain (MD, -0.93; 95% CI, -1.50 to -0.36; P = .001), CCH combination therapy showed significantly greater improvements vs CCH monotherapy. However, in the other indicators, penile curvature and PDQ psychological symptoms, there was no significant difference between the therapies.
CONCLUSIONS: This meta-analysis supports that CCH combination therapies can partially increase penile length and ameliorate symptom bother and penile pain to some extent. However, CCH combination therapies still need to be evaluated through more high-quality research.

Penis cavernosa fibrosis is an important cause of refractory erectile dysfunction.Its exact pathogenesis remains incompletely elucidated, and conventional treatment is not effective, seriously affecting the quality of life, physical and mental health of men. With the deepening of research, the progress of two-dimensional shear wave elastography (2D-SWE) and molecular imaging provides the possibility for the early diagnosis, grading and staging of cavernous fibrosis. Studies on stem cell therapy, energy-based treatments, targeted therapy, and traditional Chinese medicine show promising applications in the anti-penile cavernous fibrosis. This article reviews the research progress in the diagnosis and treatment of penile cavernosis fibrosis.

BACKGROUND: Penile induration disease, commonly known as Peyronie\'s disease (PD), is a connective tissue disorder that affects the penis, leading to the development of fibrous plaques, penile curvature, and erectile dysfunction. PD is a common male reproductive system disease with a complex etiology involving multiple genes, signaling pathways, and different phenotypes.
OBJECTIVE: The etiology and pathogenesis of PD remain poorly understood, hindering the development of effective treatment strategies. By understanding the underlying mechanisms of PD, we can pave the way for targeted therapies and improved patient outcomes.
METHODS: We reviewed the epidemiology and pathophysiology of PD. We performed database searches on Google Scholar, PubMed, Medline, and Web of Science from inception to September 2023. The literature reviewed included priapism guidelines, review articles, current trial studies, and various literature related to PD.
RESULTS: This article provides a comprehensive overview of the current research progress on the disease, focusing on its genetic factors, signaling pathways, cellular mechanisms, phenotypic manifestations, and therapeutic targets. It can help identify individuals at higher risk, aid in early detection and intervention, and provide insights into fibrosis and tissue remodeling. It can also reveal potential therapeutic targets, guide accurate diagnoses and treatment strategies, and address the impact of the disease on patients\' quality of life.
CONCLUSIONS: By integrating insights from genomics, molecular pathways, clinical phenotypes, and therapeutic potentials, our research aims to achieve a deeper and more comprehensive understanding of PD, propelling the field toward innovative strategies that enhance the lives of those affected by PD. The complex manifestations and pathogenesis of PD necessitate the use of multiple treatment methods for personalized care.

暂无摘要。

OBJECTIVE: The present study aims to explore the role of shear wave elastography (SWE) in the diagnosis of Peyronie disease (PD).
METHODS: A total of 59 PD patients and 59 age-matched healthy adult men were included in this study. The B-mode ultrasound (US) and SWE were performed for all subjects, and the Young modulus (YM) values of the corresponding regions of the penis in the PD and control groups were recorded and compared.
RESULTS: The mean age of the included PD patients and age-matched controls was 53.81 years (SD 9.52, range 32-73). On B-mode US evaluation, 41 (69.5%) of 59 included PD patients were found to have penile plaques, and the remaining 18 (30.5%) patients had no evidence of penile plaque. After evaluation using SWE, the YM values in the penile plaque region of these 41 patients with penile dysplasia were found to be significantly higher (60.29 kPa ± 19.95) than those outside the plaque (in the same patient) (21.05 kPa ± 4.58) and in the same penile region of the control group (20.59 kPa ± 4.65) (P < .001). In the remaining 18 PD patients, the results showed that the YM value of the abnormal penile region in the PD patients (56.67 kPa ± 13.52) was significantly higher than the YM value outside the abnormal penile region in the same patients (22.79 kPa ± 4.31) and in the same penile region in the control group (19.87 kPa ± 3.48) (P < .001; P < .001).
CONCLUSIONS: In conclusion, this study showed that SWE as a non-invasive technique is useful in identifying and differentiating penile plaques in PD patients and is a simple, rapid and complementary method to B-mode US.

BACKGROUND: The therapeutic role of extracorporeal shockwave therapy (ESWT) for Peyronie\'s disease (PD) has been controversial in a long term. We aimed to further evaluate the therapeutic effect of ESWT for PD on the basis of available high-quality studies.
METHODS: The PubMed, CENTRAL and Embase databases were searched for articles published from January 1st, 2000 to December 31, 2022. Only randomized controlled trials (RCTs) using ESWT to treat PD were included. Meta-analysis and forest plots were carried out using Review Manager 5.4.1 software, and outcomes were reviewed by 2 authors independently. Using the Risk of Bias assessment form (ROB-2) by Cochrane Collaboration for quality assessment. PRISMA 2020 guidelines were used in this article to achieve the quantitative and qualitative synthesis of data.
RESULTS: A total of four RCTs were included. 151 patients in the ESWT group and 150 patients in the control group. The meta-analysis results showed that ESWT could significantly reduce plaque size (OR 2.59, 95%CI 1.15 to 5.85, P = 0.02) and relieve pain (MD -1.55, 95%CI -2.46 to -0.64, P = 0.0008); but it has no significant effect on reducing the penile curvature (OR 1.93, 95%CI 0.87-4.26, P = 0.11) and improving sexual function (MD 2.6, 95%CI -1.63 to 6.83, P = 0.23), there is also no significant difference in complication rates between groups (OR 2.94, 95%CI 0.66 to 13.03, P = 0.16). The risk of bias of results is low. The limitations of this study are that the number of included studies is too small, some experimental outcomes are missing, and the expression of outcomes is not unified.
CONCLUSIONS: For PD, ESWT can be considered as a safe short-term treatment, which can reduce plaque size and relieve pain, but cannot improve penile curvature and sexual function. Its long-term efficacy remains to be discussed.
BACKGROUND: PROSPERO (ID: CRD42023436744).

This study aimed to summarize the characteristics of the top 100 most-cited publications on Peyronie\'s disease (PD) research and to analyse past and current research hotspots and trends. The SCI-E database of the Web of Science Core Collection (WoSCC) provided us with the top 100 most-cited publications in PD research, from which we took the following information: general trend of publication, year of publication, nation/region, institution, journal, author, and keywords. VOSviewer (version 1.6.18) and Excel (version 2016) were used for information analysis. Through a standardized search, we ultimately found 1019 papers in the field of PD research, from which we extracted the 100 articles that had received the highest citations. The articles were published between 1949 and 2016. The United States is a major contributor to PD research (n = 67). The University of California, Los Angeles, was the institution with the largest number of articles (n = 11). These articles were published in 16 journals, with the largest number appearing in the Journal of Urology (n = 47). The author with the most articles was Levine LA (n = 9). Gelbard MK\'s articles had the highest citation frequency (n = 1158). Erectile dysfunction (n = 19) was the keyword with the highest frequency, indicating that PD-related erectile dysfunction was the leading focus of research in this field. Most of the keywords that have appeared in the past decade are related to the clinical treatment of PD. Therefore, we believe that improving patients\' erectile function to the greatest extent in clinical treatment is the frontier and hot spot of future research.

Peyronie\'s disease (PD) is a fibrotic disorder of the penis, but effective treatments are lacking. Here, we observed the effects of rat-derived bone marrow mesenchymal stem cells (BMSCs) injection in the active phase and chronic phase in a rat model of PD, and the possible mechanism was analysed with fibroblasts derived from rat penile tunica albuginea (TA).
Thirty-two male Sprague-Dawley rats were divided into four groups. In sham group, the rats were injected with 50 µL of vehicle. In the PD group, the rats were injected with 50 µg TGF-β1. In the PD + BMSCs early treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 106 BMSCs after 1 day. In the PD + BMSCs late treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 106 BMSCs after 28 days. Twenty-seven days after the last injection, the erectile function of the rats was measured, and then, penile fibrosis was analysed by histology and western blot. In vitro, fibroblasts derived from rat penile TA were used to identify a possible antifibrotic mechanism of BMSCs, and a Smad7 expression vector was used as a positive control. Fibroblasts were pretreated with the Smad7 expression vector or BMSCs for 48 h and then activated with 10 ng/mL TGF-β1 for 24 h. Cells viability was assessed, and Smad7, collagen 3, elastase-2B and osteopontin expression levels were analysed by immunofluorescence and western blot. Furthermore, fibroblasts were transfected with Smad7 siRNA or scramble control to observe whether the effects of BMSCs could be offset.
Erectile function obviously improved, and fibrosis of penile TA was prevented after BMSCs treatment compared with that in the rats with PD. Furthermore, the effects of BMSCs treatment in the active phase were better than those in the chronic phase. After cocultured with BMSCs, cell viability was not affected, Smad7 expression was upregulated, and collagen 3, elastase-2B and osteopontin levels were decreased in the TGF-β1-treated fibroblasts. After transfection with Smad7 siRNA, the antifibrotic effects of BMSCs were offset.
The antifibrotic effects of BMSCs treatment in the active phase of the PD rat model were better than those in the chronic phase. A possible mechanism of BMSCs treatment was related to increased Smad7 expression, suggesting a possible effective and safe procedure for the treatment of PD.

Hypoxia is one of the most important predisposing conditions for Peyronie\'s disease (PD) and the pathogenetic mechanism is yet to be completely elucidated. This study applied bioinformatic approaches to select candidate hypoxia-related genes involved in the pathogenesis of PD. The Gene Expression Omnibus (GEO) data set GSE146500 was introduced to compare the transcriptional profiling between normal and PD samples. The differential expression of hypoxia-related gene was determined with R software. On the selected candidate genes, further functional analyses were applied, including protein-protein interactions (PPIs), gene correlation, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A total of 66 candidate genes (24 candidates overexpressed in PD and 42 showing reduced expression in PD) were distinguished according to the differential expression between human fibroblast cells from normal and PD patients. The interactions among these candidate genes were recognized according to PPI analysis. The functional enrichment analyses revealed the potential modulatory functions of the candidate genes in some major biological processes, especially in glycolysis/gluconeogenesis and carbon metabolism. The findings would facilitate further study on the pathogenesis of PD, which might consequently promote the improvement of clinical strategies against PD.