Background: The complex etiology and pathogenesis underlying Chronic Non-Bacterial Prostatitis (CNP), coupled with the existence of a Blood Prostate Barrier (BPB), contribute to a lack of specificity and poor penetration of most drugs. Emodin (EMO), a potential natural compound for CNP treatment, exhibits commendable anti-inflammatory, anti-oxidant, and anti-fibrosis properties but suffers from the same problems as other drugs. Methods: By exploiting the recognition properties of lactoferrin (LF) receptors that target intestinal epithelial cells (NCM-460) and prostate epithelial cells (RWPE-1), a pathway is established for the transrectal absorption of EMO to effectively reach the prostate. Additionally, hyaluronic acid (HA) is employed, recognizing CD44 receptors which target macrophages within the inflamed prostate. This interaction facilitates the intraprostatic delivery of EMO, leading to its pronounced anti-inflammatory effects. A thermosensitive hydrogel (CS-Gel) prepared from chitosan (CS) and β-glycerophosphate disodium salt (β-GP) was used for rectal drug delivery with strong adhesion to achieve effective drug retention and sustained slow release. Thus, we developed a triple-targeted nanoparticle (NPs)/thermosensitive hydrogel (Gel) rectal drug delivery system. In this process, LF, with its positive charge, was utilized to load EMO through dialysis, producing LF@EMO-NPs. Subsequently, HA was employed to encapsulate EMO-loaded LF nanoparticles via electrostatic adsorption, yielding HA/LF@EMO-NPs. Finally, HA/LF@EMO-NPs lyophilized powder was added to CS-Gel (HA/LF@EMO-NPs Gel). Results: Cellular assays indicated that NCM-460 and RWPE-1 cells showed high uptake of both LF@EMO-NPs and HA/LF@EMO-NPs, while Raw 264.7 cells exhibited substantial uptake of HA/LF@EMO-NPs. For LPS-induced Raw 264.7 cells, HA/LF@EMO-NPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways. Tissue imaging corroborated the capacity of HA/LF-modified formulations to breach the BPB, accumulating within the gland's lumen. Animal experiments showed that rectal administration of HA/LF@EMO-NPs Gel significantly reduced inflammatory cytokine expression, oxidative stress levels and fibrosis in the CNP rats, in addition to exerting anti-inflammatory effects by inhibiting the NF-κB signaling pathway without obvious toxicity. Conclusion: This triple-targeted NPs/Gel rectal delivery system with slow-release anti-inflammatory, anti-oxidant, and anti-fibrosis properties shows great potential for the effective treatment of CNP. Graphical

Evidence shows that chronic prostatitis/chronic pelvic pain syndrome hugely impacts the body and mind. The central mechanisms in patients with CP/CPPS resulted in increased attention as neuroimaging techniques developed. This review investigated the study design and major neuroimaging findings in CP/CPPS patients to provide comprehensive evidence. Seven databases were searched and screened: PubMed, EMBASE/SCOPUS, Cochrane Library Database, China National Knowledge Infrastructure, VIP, Wanfang, and China Biology Medicine disc. Nine studies were eventually included in the analysis. The results demonstrate that the insula, anterior cingulate gyrus, postcentral gyrus, and precuneus are significantly associated with CP/CPPS patients’ pain feelings and cause dysregulation of painful emotions, lowering patients’ tolerance to stimulus.

Previous studies had illustrated the significant neural pathological changes in patients with psychogenic erectile dysfunction (pED), while few works focused on the neural underpinning of the psychosocial status in patients with pED. This study aimed to investigate the associations among the altered cerebral activity patterns, impaired erectile function, and the disrupted psychosocial status in patients with pED. Thirty-two patients with pED and 28 healthy controls (HCs) were included. The amplitude of low-frequency fluctuations (ALFF), region-of-interest-based functional connectivity (FC), as well as Pearson correlation analyses and mediation analyses between neuroimaging outcomes and clinical outcomes were performed. Compared to HCs, patients with pED manifested lower erectile function, disrupted psychosocial status, as well as decreased ALFF in the left dorsolateral prefrontal cortex (dlPFC) and reduced FC between the left dlPFC and left angular gyrus, and left posterior cingulate cortex (PCC) and precuneus, which belonged to the default mode network (DMN). Moreover, both the ALFF of the left dlPFC and FC between the left dlPFC and left PCC and precuneus were significantly correlated with the sexual function and psychosocial status in patients with pED. The disrupted psychosocial status mediated the influence of atypical FC between dlPFC and DMN on decreased erectile function. This study widened our understanding of the important role of psychosocial disorders in pathological neural changes in patients with pED.

Background: Low-intensity extracorporeal shockwave therapy (LI-ESWT) may be a successful complementary treatment approach for erectile dysfunction (ED). In this study, we aimed to review and summarize the research evidence from systematic reviews (SRs)/meta-analyses (MAs) regarding the clinical effectiveness of LI-ESWT for ED. Methods: Studies on LI-ESWT for ED were searched using eight electronic databases from establishment of each database to 31 June 2021 with the language restrictions of Chinese and English. All articles were screened, and qualifying data were recorded based on the inclusion criteria. Methods including: the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2); the Risk of Bias in Systematic Reviews (ROBIS); the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); and Grading of Recommendations, Assessment Development, and the Evaluation (GRADE) were used by two independent raters to assess methodological quality, risk of bias, reporting quality, and SR evidence of quality, respectively. Results: Eight SRs/MAs met all inclusion criteria. Seven reviews were rated as critically low on overall confidence and one review was low on confidence based on the AMSTAR-2 appraisal tool. While most PRISMA criteria were met, the major reporting flaws were in relation the financial statements not being included, along with no protocol registrations. Three SRs/MAs were classed as low risk regarding bias as measured by the ROBIS tool. Based on the GRADE method, only one SRs/MAs of high-quality evidence and seven SRs/MAs of moderate-quality evidence were found. The present research results supported LI-ESWT as a complementary therapy for ED patients, but the evidence should be considered carefully due to the methodological flaws identified. Discussion: Our results showed that LI-ESWT as an adjunctive therapy has benefits for ED patients. There were no obvious side effects, and the number of shockwave treatments and energy flux density (EFD) would affect the IIEF-EF, EHS and PSV scores. However, due to the limited sample size and the quality of reporting evidence, our conclusions may not be fully representative.

Introduction Erectile dysfunction (ED) is the most common male sexual disorder that severely impacts the sexual performance and quality of life of men. As the main subtype of ED, psychogenic ED (pED) has been demonstrated to be a genitourinary disease and also associated with alterations in both brain structure and function. However, the scattered neuroimaging evidence from individual studies has not yet been integrated, and the central pathological alterations associated with pED remain unclear. The objective of this systematic review is to integrate and assess the evidence of the impact of pED on brain structure and function. Methods and analysis Five databases (PubMed, EMBASE, Web of Science, China Biology Medicine Database and China National Knowledge Infrastructure (CNKI)) will be systematically searched from inception to 1 October 2019 (the anticipated completion date of this review), with language restricted to English and Chinese. Studies focusing on the structural or functional alterations in patients with pED will be retrieved. The study selection process will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline and quality assessment will be conducted with a customised checklist. After data extraction, a qualitative review will be performed to synthesise the structural and functional brain alterations as well as the correlations between the altered cerebral structures and functions and the clinical characteristics of patients with pED. If the collected data make it feasible, an activation likelihood estimation meta-analysis will also be launched. Ethics and dissemination Ethical approval is not required as primary data will not be collected. This review will be published in a peer-reviewed journal and presented at conferences. PROSPERO registration number CRD42019117206.