Background:Chronic inflammation is closely associated with the most common and socially significant prostate conditions,including benign prostatic hyperplasia(BPH),prostate cancer(PCa),and prostatitis syndromes.NIHcat...Background:Chronic inflammation is closely associated with the most common and socially significant prostate conditions,including benign prostatic hyperplasia(BPH),prostate cancer(PCa),and prostatitis syndromes.NIHcategory IV prostatitis(histologic prostatitis,HP)is defined as asymptomatic chronic inflammation of the prostate.The presence of lymphoid follicles,referred to as tertiary lymphoid structures(TLSs),along with benign lympho-epithelial lesions(BLELs),is among the key histological indicators of immune inflammation and can be assessed relatively easily.This study aimed to quantitatively assess TLSs and BLELs,as well as their relationship with the severity of HP.Methods:We investigated TLSs and BLELs in 110 prostatic specimens,including inflammatory and normal tissues,within the context of common prostate pathologies such as BPH and PCa.HP was graded as low-grade(LG)or high-grade(HG)based on the severity of inflammation.Results:TLSs were observed in 51 out of 110 cases(46.4%),while BLELs were identified in 78 cases(70.44%).Both TLSs and BLELs co-occurred in 45 cases(40.9%).Statistical analysis revealed a significant correlation between the presence of TLSs,BLELs(individually or combined),and HG-HP(p<0.001).Conclusions:This study is the first to quantitatively evaluate the immunopathologic patterns in the inflamed human prostate by analyzing the presence and cooccurrence of TLSs and BLELs.Their formation,likely triggered by antigenic stimuli and external factors,indicates a chronic inflammatory microenvironment.The strong association between TLSs,BLELs,and HG-HP underscores their potential role in HP aggressiveness.These findings suggest that TLSs and BLELs may be crucial contributors to the pathophysiology and morphogenesis of NIH-category IV prostatitis.Furthermore,TLS/BLEL formation may represent a hallmark of tissue autoimmunity,reflecting the immune or autoimmune phase of this prostatitis subtype.展开更多
Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a complex disease that is often accompanied by mental health disorders.However,the potential mechanisms underlying the heterogeneous clinical presentation of...Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a complex disease that is often accompanied by mental health disorders.However,the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain.This study analyzed widely targeted metabolomic data of expressed prostatic secretions(EPS)and plasma to reveal the underlying pathological mechanisms of CP/CPPS.A total of 24 CP/CPPS patients from The Second Nanning People’s Hospital(Nanning,China),and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University(Nanning,China)were enrolled.The indicators related to CP/CPPS and psychiatric symptoms were recorded.Differential analysis,coexpression network analysis,and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS.The crucial links between EPS and plasma were further investigated.The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals.Pathway analysis revealed dysregulation of amino acid metabolism,lipid metabolism,and the citrate cycle in EPS.The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes.Moreover,the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS.Overall,metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage,energy metabolism abnormalities,neurological impairment,and immune dysregulation.These alterations may be associated with chronic pain,voiding symptoms,reduced fertility,and depression in CP/CPPS.This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.展开更多
The aim of this study is to observe the therapeutic effect of Inonotus Obliquus Polysaccharide(IOP)on chronic nonbacterial prostatitis(CNP)and its effect on the helper T cells(Th17)and regulatory T cells(Treg)immune i...The aim of this study is to observe the therapeutic effect of Inonotus Obliquus Polysaccharide(IOP)on chronic nonbacterial prostatitis(CNP)and its effect on the helper T cells(Th17)and regulatory T cells(Treg)immune imbalance.The CNP rat models established by injecting Xiaozhiling injection were randomly divided into the model group,cernilton(40 mg/kg,i.g.)group and low-dose(35 mg/kg,i.g.),medium-dose(70 mg/kg,i.g.)and high-dose(140 mg/kg,i.g.)groups,with the same volume of saline injected into the same site as the control group.The prostate’s wet weight and body mass served as the basis for calculating the prostate index.The serum level of prostate-specific antigen(PSA)was detected by ELISA and the histopathology of prostate tissue was detected by HE staining.The protein expression of Foxp3,ROR-γt and STAT3 in rat prostatic tissue was determined by Western blot.The levels of Th17 and Treg cells infiltrated into the spleen were measured by flow cytometry.The results showed that treatment with IOP significantly reduced the levels of prostate index and serum PSA,and attenuated the pathological injury of the prostate tissue induced by CNP.With respect to samples induced by CNP alone,IOP treatment repressed the increased mRNA levels of IL-6,IL-17,IL-21,IL-23,ROR-γt and STAT3 in prostate tissue,while increasing the mRNA levels of IL-10,TGF-βand Foxp3 in prostate tissue.Meanwhile,IOP treatment attenuated the upregulation of the protein expression levels of ROR-γt and STAT3 in prostate tissue.Additionally,the protein expression of Foxp3 in prostate tissue was increased in the IOP-treated group.Flow cytometry analysis further demonstrated that IOP treatment regulated the balance between Th17 and Treg cells in the spleen in rat with CNP.Our study is the first to elucidate that IOP has significant therapeutic effects on CNP through regulation of Th17/Treg balance.Collectively,the study provides evidence for the potential of IOP to treat CNP.展开更多
Background:Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain.Proinflammatory T helper 17(Th17)cells are essenti...Background:Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain.Proinflammatory T helper 17(Th17)cells are essential for triggering the development of CP/CPPS.High-salt diet(HSD)consumption has been found to cause an accumulation of sodium chloride in peripheral organs,inducing autoimmune responses via the Th17 cell axis.It is currently unknown whether HSD affects the etiology and course of CP/CPPS.Methods:Patients diagnosed with CP/CPPS were evaluated with the National Institutes of Health Chronic Prostatitis Symptom Index scoring system,and the correlation between the symptoms of CP/CPPS with HSD was analyzed.The experimental autoimmune prostatitis(EAP)mouse was established and the mice were fed either a normal-salt diet(NSD)or HSD for 6 weeks to investigate the impact of HSD on CP/CPPS.Then,16S ribosomal RNA sequencing and untargeted metabolomics were introduced to detect the differences in the gut microflora composition and metabolite profiles between NSD-fed and HSD-fed mice,followed by fecal microbiota transplantation,5-hydroxyindole acetic acid(5-HIAA)supplementation,aryl hydrocarbon receptor(AHR)inhibition,and in vitro Th17 differentiation experiments,which were performed to explore the mechanisms underlying HSD-aggravated CP/CPPS.Finally,chromatin immunoprecipitation assay and quantitative polymerase chain reaction were conducted to validate whether AHR can serve as a transcription factor by interacting with the serum and glucocorticoid-regulated kinase 1(Sgk1)promoter in CD4^(+)T cells.Results:Increased salt consumption had a positive correlation with symptom scores of CP/CPPS patients,which was validated by feeding EAP mice with HSD,and HSD worsened the prostate inflammation and tactile allodynia in EAP mice through promoting the differentiation of CD4^(+)T cells to Th17 cells.HSD exacerbated EAP by significantly reducing the relative abundance of beneficial gut microflora,such as Lactobacillaceae,and gut microbiota metabolite 5-HIAA,which is related to tryptophan metabolism.The prostate inflammation,tactile allodynia,and proportion of Th17 cells in mice that received fecal suspensions from the EAP^(+)HSD group were significantly more severe or higher than those in mice that received fecal suspensions from the EAP^(+)NSD group.However,5-HIAA supplementation ameliorated the symptoms of EAP caused by HSD through inhibiting the differentiation of CD4^(+)T cells to Th17 cells,while AHR inhibition abrogated the protective effects of 5-HIAA supplementation on EAP mice fed a HSD through promoting the differentiation of CD4^(+)T cells to Th17 cells.Mechanistically,it has been revealed that the SGK1/forkhead box protein O1(FOXO1)pathway was significantly activated during cytokine-induced Th17 cell differentiation,and AHR has been shown to inhibit SGK1 transcription by interacting with the Sgk1 promoter in CD4^(+)T cells to inhibit FOXO1 phosphorylation,consequently restoring the equilibrium of Th17 cell differentiation.Conclusions:Our findings indicated that high salt intake represented a risk factor for the development of CP/CPPS as it promoted the differentiation of CD4^(+)T cells to Th17 cells through the 5-HIAA/AHR/SGK1/FOXO1 axis,which might be a potential therapeutic target for CP/CPPS.展开更多
OBJECTIVE:To investigate the protective effects of Guilong prescription(归龙方,GL)on chronic prostatitis(CP)and unravel the underlying mechanisms of its pharmacological effects.METHODS:The composition of GL was determ...OBJECTIVE:To investigate the protective effects of Guilong prescription(归龙方,GL)on chronic prostatitis(CP)and unravel the underlying mechanisms of its pharmacological effects.METHODS:The composition of GL was determined via linear ion trap/electrostatic field orbital trap tandem highresolution mass spectrometry,and the identified compounds were performed network pharmacological analysis to predict possible pathways of the effects of GL on CP.A CP rat model was established by carrageenan,and rats were randomly assigned into a Control group,Sham group,CP group,GL low dose(3.5 g/kg)group,GL medium dose(7 g/kg)group,and GL high dose(14 g/kg)group.Hematoxylin-eosin staining of the prostate,and prostate blood-perfusion measured by laser speckle contrast analysis were used to evaluate the efficacy of GL.Expression of intercellular cell adhesion molecule-1(ICAM-1)and induce nitric oxide synthase(i NOS)were determined by immunohistochemistry,and the content of interferon-γ(IFN-γ),interleukin-1β(IL-1β),interleukin-4(IL-4),interleukin-10(IL-10),chemokine ligand 1(CXCL1)and tumor necrosis factor-α(TNF-α)were determined by electro-chemiluminescence assays.The expression of p38 mitogen-activated protein kinase(p38 MAPK),phosphatidylinositol 3-kinase(PI3K),ribosomeassociated complex-alpha serine/threonine-protein kinase(Akt),nuclear factor-κ-gene binding p65(NF-κB p65),inhibitor of NF-κB-α(IκBα),glycogen synthase kinase-3β(GSK-3β),and their phosphorylated forms were tested by Western blot.RESULTS:In GL,a total of 48 compounds were identified,including 14 flavonoids,14 alkaloids,11 carboxylic acids,4 lactones,2 glycosides,2 terpenoids and 1 aldehyde.Network pharmacological analysis suggested that the mechanism of GL may be related to PI3K-Akt signaling pathway and cytokine expression.After treatment with GL,inflammatory pathological changes in the prostate of rats were significantly improved,and blood perfusion of the prostate was significantly decreased.GL reduced the expression of IFN-γ,CXCL1,TNF-α,IL-1β,i NOS,ICAM-1,p38 MAPK,p-p38 MAPK,PI3K,p-PI3K,NF-κB,p-NF-κB,IκBα,p-IκBα,GSK-3β,p-GSK-3β,p-Akt in CP rats,and increased the expression of IL-4 and IL-10 in CP rats.CONCLUSION:The chemical compositions of GL were first identified.GL can improve pathological changes in the prostate and recover the prostate blood perfusion of CP rats.The possible mechanisms of GL on CP involve increasing the expression of anti-inflammatory cytokines IL-4 and IL-10,inhibiting pro-inflammatory cytokines TNF-α,IL-1β,and IFN-γ,and down regulating the expression of CXCL1,i NOS,and ICAM-1 via inhibiting PI3K-Akt and NF-κB signaling pathway.展开更多
Prostatitis is a common genitourinary disease characterized by a complex pathogenesis involving infection,inflammation,oxidative stress,and immune dysfunction.The p38MAPK signaling pathway plays a key role in inflamma...Prostatitis is a common genitourinary disease characterized by a complex pathogenesis involving infection,inflammation,oxidative stress,and immune dysfunction.The p38MAPK signaling pathway plays a key role in inflammation and stress response,and inhibition of this pathway can reduce the expression of inflammatory factors,thereby alleviating prostatitis.Studies have shown that traditional Chinese medicine can effectively treat prostatitis by regulating p38MAPK pathway.In this study,the role of p38MAPK in prostatitis is discussed through literature review,which provides a new scientific basis for the treatment of traditional Chinese medicine.展开更多
Androgen deprivation therapy(ADT)can negatively affect sexual function,and only a minority of patients report sexual activity.We reviewed the existing literature regarding the proportion of men who remained sexually a...Androgen deprivation therapy(ADT)can negatively affect sexual function,and only a minority of patients report sexual activity.We reviewed the existing literature regarding the proportion of men who remained sexually active during and after ADT.The PubMed database was searched for studies published over the past 20 years.We selected and reviewed randomized clinical trials that provided sexual function data at baseline and during and after ADT.The primary outcome measure was the sexual function.Studies assessed sexual function using quality of life patient-reported outcome measures,which included sexual potency/activity evaluation.Information from 2947 patients was analyzed in this review.The median age of patients was 70 years.At baseline,a median of 49.9%(95%confidence interval[Cl]:49.1%-50.7%)of the patients reported being sexually active.At 6 months,12 months,and 2 years or later of ADT treatment,a median of 10.3%(95%Cl:10.2%-10.5%),8.9%(95%Cl:8.6%-9.2%),and 8.3%(95%Cl:8.2%-8.5%)of the patients reported being sexually active,respectively.Considering that half of the patients were sexually active at baseline,it seems probable that more than 10%of the patients who were sexually active before starting ADT remained sexually active when undergoing ADT.In conclusion,despite the common belief that ADT eliminates sexual activity,this analysis found that approximately 1 in 10 men are sexually active when on ADT,and this proportion is likely increased in men who are sexually active before starting ADT.Attention to sexual activity should not be dismissed in men on ADT.展开更多
Objective:Current research highlights periodontal disease as a systemic inflammatory condition that may influence extra-oral diseases such as prostatic diseases,which prompted us to explore the potential association.T...Objective:Current research highlights periodontal disease as a systemic inflammatory condition that may influence extra-oral diseases such as prostatic diseases,which prompted us to explore the potential association.To evaluate whether periodontal disease is associated with an increased risk of prostatic disease,including prostate cancer,benign prostatic hyperplasia(BPH),and prostatitis.Methods:A systematic search of observational studies concerning the relationship between periodontal disease and prostatic disease was performed in online databases PubMed,Embase,Web of Science,Scopus,CENTRAL,CNKI,and WanFang.Searches were conducted from database inception to 31 July 2025.Pooled hazard ratio(HR)or odds ratio(OR)with 95%confidence intervals(CIs)were synthesized.Subgroup analysis was used to detect the origin of heterogeneity,sensitivity analysis was employed to evaluate the robustness of the results,and publication bias analyses were also performed.R software was used to perform statistical analyses.Results:Sixteen studies that met the preset criteria were included in this study.In the pooled analysis,periodontal disease was associated with increased risk of prostate cancer(HR=1.23,95%CI:1.16-1.29,p<0.001)or BPH(OR=1.55,95%CI:1.41-1.70,p<0.001).Sensitivity analysis confirmed the robustness of the results.No obvious publication biaswas found in the meta-analysis.Only one cohort study reported that chronic periodontitis increases the risk of prostatitis(HR=2.521,95%CI:1.685-4.005,p<0.001).The effect of periodontal treatment on prostatic disease is still unclear.Conclusions:The systematic review and meta-analysis identified an observational association between periodontal disease and increased risks of prostate cancer and BPH.Because all included studies were observational,these results indicate association rather than causation,and further prospective and mechanistic studies are required to clarify temporality and causality.展开更多
Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype ...Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.展开更多
Background:Prostate cancer is a common malignancy,with many men on active surveillance for localized,low-risk disease also experiencing lower urinary tract symptoms(LUTS)from benign prostatic hyperplasia(BPH).Water Va...Background:Prostate cancer is a common malignancy,with many men on active surveillance for localized,low-risk disease also experiencing lower urinary tract symptoms(LUTS)from benign prostatic hyperplasia(BPH).Water Vapor Thermal Therapy(WVTT)is a minimally invasive BPH treatment,but its safety and efficacy in this setting are unclear.Case Description:We report three men with localized PCa on active surveillance who underwent WVTT for LUTS.Conclusions:WVTT appears safe and potentially effective in treating LUTS,especially in those with lower-risk disease and smaller prostate volumes.Further research is needed to confirm safety,efficacy,and optimal patient selection.展开更多
Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advanc...Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advancements,transurethral approaches continue to pose risks such as urethral strictures and urinary incontinence due to mechanical and thermal stress.To address these limitations,the Suprapubic Transvesical Adenoma Resection of the Prostate(STARP)was developed,offering a direct suprapubic route that bypasses the urethra entirely.Recent studies have validated STAR-P as both feasible and safe,emphasizing advantages such as enhanced visualization of the urinary sphincter,minimized urethral trauma,effective hemostasis,and reduced operative stress.The procedure utilizes specially designed instrumentation,including a large-caliber bipolar resectoscope(42 Fr),allowing the efficient removal of substantial adenoma tissue in fewer resection passes compared to traditional methods.Objectives:This article provides a comprehensive,step-by-step description of the STAR-P technique.The primary objective is to detail patient selection criteria,preoperative assessments,procedural steps including mini-open suprapubic access,specialized instrumentation usage,resection techniques,and postoperative management protocols.Highlighting technical considerations and procedural innovations aims to inform urologists about the potential benefits of STAR-P,particularly in patients at higher risk for urethral complications or those with large prostate volumes.By documenting the procedural intricacies and outcomes clearly and thoroughly,we seek to encourage informed adoption of STAR-P as an alternative,effective surgical approach for managing benign prostatic hyperplasia,thus contributing to the evolving landscape ofminimally invasive urological surgery.展开更多
Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated...Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated with dynamic real-time low-dose rate(LDR)brachytherapy using Iodine 125(I^(125)).Methods:We retrospectively reviewed 499 patients with localized prostate cancer treated with I^(125) LDR realtime brachytherapy between 2003 and 2021.The mean patient age was 65 years(range:45–84 years).Based on the National Comprehensive Cancer Network(NCCN)risk classification,230 patients(46.1%)were categorized as low risk,235(47.1%)as intermediate risk,and 34(6.8%)as high risk.Gleason scores were distributed as follows:3+3 in 283 cases(56.7%),3+4 in 157 cases(31.5%),4+3 in 46 cases(9.2%),and 4+4 in 13 cases(2.6%).The mean follow-up was 70.5 months.Results:Tumor relapse was observed in 47 patients(9.4%)over a mean follow-up period of 6.26 years(SD 4.16).Local recurrence within the prostate occurred in 20 cases(4%).Patients with nadir PSA<0.2 ng/mL at 5 years of follow-up had a significantly lower incidence of tumor recurrence(3%)compared to those with a nadir PSA>0.2 ng/mL(21.9%)(p=0.0001).Biochemical relapse-free(BRFS)rates at 5,10 and 15 years were 96%,91.5% and 88.9%,respectively.When stratified by NCCCN risk groups,5-year BRFS was 96% in low risk,98% in intermediate risk and 85% in high risk patients(p=0.003).Inmultivariate analysis,only age at the time of brachytherapy(p=0.009),initial PSA(p=0.007)and Gleason grade(p=0.007)were significantly associated with tumor recurrence.Cancer-specific survival and overall survival were 99.8% and 98.0%,respectively.Conclusions:LDR with I^(125) has excellent longterm oncological outcomes for patients with low and intermediate-risk prostate cancer,in particular,patients achieving a nadir PSA<0.2 ng/mL at 5 years post-treatment.展开更多
Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated signi...Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.展开更多
Prostatic carcinoma(PCa)has become one of the most common cancers among men worldwide,with both incidence and mortality rates steadily rising.Although current treatments are effective in the early stages of PCa,many c...Prostatic carcinoma(PCa)has become one of the most common cancers among men worldwide,with both incidence and mortality rates steadily rising.Although current treatments are effective in the early stages of PCa,many cases eventually progress to castration-resistant prostate cancer(CRPC),and led to treatment failure.To develop new therapeutic strategies to ameliorate the survival of PCa patients then has pressed the need on medicinal researchers.Of traditional Chinese medicinal herbs,Angelica gigas Naka(AGN),and its major pyranocoumarins were broadly reported on the effect of anti-PCa.However,existing reviews mainly focus on decursin(D),decursinol angelate(DA),and decursinol(DOH),without fully exploring other coumarins in AGN.Moreover,most reviews discuss general anticancer effects,with limited emphasis on PCa specifically.This review made a comprehensive summary of the coumarin components of AGN,and depicted the anti-PCa effects and mechanisms,giving a solid research support for drug discovery and development.This review also featured pharmacokinetic advantages and therapeutic potential of DOH,in order to suggest possibilities to overcome the in vivo transformation limitations of D and DA,and shed light on CRPC treatment.We also recommend future studies focus on more in vivo evidence,safety and toxicity evaluation,and clinical validation in humans.展开更多
Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly can...Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.展开更多
Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim ...Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.展开更多
Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(P...Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.展开更多
文摘Background:Chronic inflammation is closely associated with the most common and socially significant prostate conditions,including benign prostatic hyperplasia(BPH),prostate cancer(PCa),and prostatitis syndromes.NIHcategory IV prostatitis(histologic prostatitis,HP)is defined as asymptomatic chronic inflammation of the prostate.The presence of lymphoid follicles,referred to as tertiary lymphoid structures(TLSs),along with benign lympho-epithelial lesions(BLELs),is among the key histological indicators of immune inflammation and can be assessed relatively easily.This study aimed to quantitatively assess TLSs and BLELs,as well as their relationship with the severity of HP.Methods:We investigated TLSs and BLELs in 110 prostatic specimens,including inflammatory and normal tissues,within the context of common prostate pathologies such as BPH and PCa.HP was graded as low-grade(LG)or high-grade(HG)based on the severity of inflammation.Results:TLSs were observed in 51 out of 110 cases(46.4%),while BLELs were identified in 78 cases(70.44%).Both TLSs and BLELs co-occurred in 45 cases(40.9%).Statistical analysis revealed a significant correlation between the presence of TLSs,BLELs(individually or combined),and HG-HP(p<0.001).Conclusions:This study is the first to quantitatively evaluate the immunopathologic patterns in the inflamed human prostate by analyzing the presence and cooccurrence of TLSs and BLELs.Their formation,likely triggered by antigenic stimuli and external factors,indicates a chronic inflammatory microenvironment.The strong association between TLSs,BLELs,and HG-HP underscores their potential role in HP aggressiveness.These findings suggest that TLSs and BLELs may be crucial contributors to the pathophysiology and morphogenesis of NIH-category IV prostatitis.Furthermore,TLS/BLEL formation may represent a hallmark of tissue autoimmunity,reflecting the immune or autoimmune phase of this prostatitis subtype.
基金supported by the National Natural Science Foundation of China(No.81770759 and No.82270806)Innovation Project of Guangxi Graduate Education(No.YCBZ2022094).
文摘Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a complex disease that is often accompanied by mental health disorders.However,the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain.This study analyzed widely targeted metabolomic data of expressed prostatic secretions(EPS)and plasma to reveal the underlying pathological mechanisms of CP/CPPS.A total of 24 CP/CPPS patients from The Second Nanning People’s Hospital(Nanning,China),and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University(Nanning,China)were enrolled.The indicators related to CP/CPPS and psychiatric symptoms were recorded.Differential analysis,coexpression network analysis,and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS.The crucial links between EPS and plasma were further investigated.The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals.Pathway analysis revealed dysregulation of amino acid metabolism,lipid metabolism,and the citrate cycle in EPS.The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes.Moreover,the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS.Overall,metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage,energy metabolism abnormalities,neurological impairment,and immune dysregulation.These alterations may be associated with chronic pain,voiding symptoms,reduced fertility,and depression in CP/CPPS.This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
基金Shanxi Province Traditional Chinese Medicine Administration Research Project(Grant No.2022ZYYC094)Science and technology innovation project of universities in Shanxi Province(Grant No.2022L342)+1 种基金Shanxi Leader Team of Medical Science&Technology Innovations(Grant No.2020TD02)Discipline Construction Project of Chinese Medicine Chemistry(Grant No.2024XKJS-25).
文摘The aim of this study is to observe the therapeutic effect of Inonotus Obliquus Polysaccharide(IOP)on chronic nonbacterial prostatitis(CNP)and its effect on the helper T cells(Th17)and regulatory T cells(Treg)immune imbalance.The CNP rat models established by injecting Xiaozhiling injection were randomly divided into the model group,cernilton(40 mg/kg,i.g.)group and low-dose(35 mg/kg,i.g.),medium-dose(70 mg/kg,i.g.)and high-dose(140 mg/kg,i.g.)groups,with the same volume of saline injected into the same site as the control group.The prostate’s wet weight and body mass served as the basis for calculating the prostate index.The serum level of prostate-specific antigen(PSA)was detected by ELISA and the histopathology of prostate tissue was detected by HE staining.The protein expression of Foxp3,ROR-γt and STAT3 in rat prostatic tissue was determined by Western blot.The levels of Th17 and Treg cells infiltrated into the spleen were measured by flow cytometry.The results showed that treatment with IOP significantly reduced the levels of prostate index and serum PSA,and attenuated the pathological injury of the prostate tissue induced by CNP.With respect to samples induced by CNP alone,IOP treatment repressed the increased mRNA levels of IL-6,IL-17,IL-21,IL-23,ROR-γt and STAT3 in prostate tissue,while increasing the mRNA levels of IL-10,TGF-βand Foxp3 in prostate tissue.Meanwhile,IOP treatment attenuated the upregulation of the protein expression levels of ROR-γt and STAT3 in prostate tissue.Additionally,the protein expression of Foxp3 in prostate tissue was increased in the IOP-treated group.Flow cytometry analysis further demonstrated that IOP treatment regulated the balance between Th17 and Treg cells in the spleen in rat with CNP.Our study is the first to elucidate that IOP has significant therapeutic effects on CNP through regulation of Th17/Treg balance.Collectively,the study provides evidence for the potential of IOP to treat CNP.
基金supported by the National Natural Science Foundation of China(82300872 and 82170787)the Anhui Provincial Natural Science Foundation(2408085Y038)+3 种基金the Supporting Projects for Innovative Leading Talents(T000529)the Distinguished Young Scholar of Anhui Colleges(2021-108-10)the Science Foundation for Outstanding Young Scholar of Anhui Colleges(2022AH020073)the Sanming Project of Medicine in Shenzhen Nanshan(SZSM20210300).
文摘Background:Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain.Proinflammatory T helper 17(Th17)cells are essential for triggering the development of CP/CPPS.High-salt diet(HSD)consumption has been found to cause an accumulation of sodium chloride in peripheral organs,inducing autoimmune responses via the Th17 cell axis.It is currently unknown whether HSD affects the etiology and course of CP/CPPS.Methods:Patients diagnosed with CP/CPPS were evaluated with the National Institutes of Health Chronic Prostatitis Symptom Index scoring system,and the correlation between the symptoms of CP/CPPS with HSD was analyzed.The experimental autoimmune prostatitis(EAP)mouse was established and the mice were fed either a normal-salt diet(NSD)or HSD for 6 weeks to investigate the impact of HSD on CP/CPPS.Then,16S ribosomal RNA sequencing and untargeted metabolomics were introduced to detect the differences in the gut microflora composition and metabolite profiles between NSD-fed and HSD-fed mice,followed by fecal microbiota transplantation,5-hydroxyindole acetic acid(5-HIAA)supplementation,aryl hydrocarbon receptor(AHR)inhibition,and in vitro Th17 differentiation experiments,which were performed to explore the mechanisms underlying HSD-aggravated CP/CPPS.Finally,chromatin immunoprecipitation assay and quantitative polymerase chain reaction were conducted to validate whether AHR can serve as a transcription factor by interacting with the serum and glucocorticoid-regulated kinase 1(Sgk1)promoter in CD4^(+)T cells.Results:Increased salt consumption had a positive correlation with symptom scores of CP/CPPS patients,which was validated by feeding EAP mice with HSD,and HSD worsened the prostate inflammation and tactile allodynia in EAP mice through promoting the differentiation of CD4^(+)T cells to Th17 cells.HSD exacerbated EAP by significantly reducing the relative abundance of beneficial gut microflora,such as Lactobacillaceae,and gut microbiota metabolite 5-HIAA,which is related to tryptophan metabolism.The prostate inflammation,tactile allodynia,and proportion of Th17 cells in mice that received fecal suspensions from the EAP^(+)HSD group were significantly more severe or higher than those in mice that received fecal suspensions from the EAP^(+)NSD group.However,5-HIAA supplementation ameliorated the symptoms of EAP caused by HSD through inhibiting the differentiation of CD4^(+)T cells to Th17 cells,while AHR inhibition abrogated the protective effects of 5-HIAA supplementation on EAP mice fed a HSD through promoting the differentiation of CD4^(+)T cells to Th17 cells.Mechanistically,it has been revealed that the SGK1/forkhead box protein O1(FOXO1)pathway was significantly activated during cytokine-induced Th17 cell differentiation,and AHR has been shown to inhibit SGK1 transcription by interacting with the Sgk1 promoter in CD4^(+)T cells to inhibit FOXO1 phosphorylation,consequently restoring the equilibrium of Th17 cell differentiation.Conclusions:Our findings indicated that high salt intake represented a risk factor for the development of CP/CPPS as it promoted the differentiation of CD4^(+)T cells to Th17 cells through the 5-HIAA/AHR/SGK1/FOXO1 axis,which might be a potential therapeutic target for CP/CPPS.
基金National Major Scientific and the Technological Special Project:Establishment of a Clinically Oriented Preclinical Research and Development Technology Platform for New Chinese Medicines based on Famous Doctors'Prescriptions(No.2017ZX09301011)"Decoding Traditional Chinese Medicine"Project of Beijing University of Chinese Medicine:New Drugs Research and Development of Chinese Medicine based on Famous Doctors and Famous Prescriptions(No.90010961020020)the Horizontal Project:Preclinical Pharmacology and Pharmacodynamic Research of a New Chinese Medicine—Guilong Granules(No.2016110031007799)。
文摘OBJECTIVE:To investigate the protective effects of Guilong prescription(归龙方,GL)on chronic prostatitis(CP)and unravel the underlying mechanisms of its pharmacological effects.METHODS:The composition of GL was determined via linear ion trap/electrostatic field orbital trap tandem highresolution mass spectrometry,and the identified compounds were performed network pharmacological analysis to predict possible pathways of the effects of GL on CP.A CP rat model was established by carrageenan,and rats were randomly assigned into a Control group,Sham group,CP group,GL low dose(3.5 g/kg)group,GL medium dose(7 g/kg)group,and GL high dose(14 g/kg)group.Hematoxylin-eosin staining of the prostate,and prostate blood-perfusion measured by laser speckle contrast analysis were used to evaluate the efficacy of GL.Expression of intercellular cell adhesion molecule-1(ICAM-1)and induce nitric oxide synthase(i NOS)were determined by immunohistochemistry,and the content of interferon-γ(IFN-γ),interleukin-1β(IL-1β),interleukin-4(IL-4),interleukin-10(IL-10),chemokine ligand 1(CXCL1)and tumor necrosis factor-α(TNF-α)were determined by electro-chemiluminescence assays.The expression of p38 mitogen-activated protein kinase(p38 MAPK),phosphatidylinositol 3-kinase(PI3K),ribosomeassociated complex-alpha serine/threonine-protein kinase(Akt),nuclear factor-κ-gene binding p65(NF-κB p65),inhibitor of NF-κB-α(IκBα),glycogen synthase kinase-3β(GSK-3β),and their phosphorylated forms were tested by Western blot.RESULTS:In GL,a total of 48 compounds were identified,including 14 flavonoids,14 alkaloids,11 carboxylic acids,4 lactones,2 glycosides,2 terpenoids and 1 aldehyde.Network pharmacological analysis suggested that the mechanism of GL may be related to PI3K-Akt signaling pathway and cytokine expression.After treatment with GL,inflammatory pathological changes in the prostate of rats were significantly improved,and blood perfusion of the prostate was significantly decreased.GL reduced the expression of IFN-γ,CXCL1,TNF-α,IL-1β,i NOS,ICAM-1,p38 MAPK,p-p38 MAPK,PI3K,p-PI3K,NF-κB,p-NF-κB,IκBα,p-IκBα,GSK-3β,p-GSK-3β,p-Akt in CP rats,and increased the expression of IL-4 and IL-10 in CP rats.CONCLUSION:The chemical compositions of GL were first identified.GL can improve pathological changes in the prostate and recover the prostate blood perfusion of CP rats.The possible mechanisms of GL on CP involve increasing the expression of anti-inflammatory cytokines IL-4 and IL-10,inhibiting pro-inflammatory cytokines TNF-α,IL-1β,and IFN-γ,and down regulating the expression of CXCL1,i NOS,and ICAM-1 via inhibiting PI3K-Akt and NF-κB signaling pathway.
基金Supported by Natural Science Foundation of Hainan Province(820RC788).
文摘Prostatitis is a common genitourinary disease characterized by a complex pathogenesis involving infection,inflammation,oxidative stress,and immune dysfunction.The p38MAPK signaling pathway plays a key role in inflammation and stress response,and inhibition of this pathway can reduce the expression of inflammatory factors,thereby alleviating prostatitis.Studies have shown that traditional Chinese medicine can effectively treat prostatitis by regulating p38MAPK pathway.In this study,the role of p38MAPK in prostatitis is discussed through literature review,which provides a new scientific basis for the treatment of traditional Chinese medicine.
文摘Androgen deprivation therapy(ADT)can negatively affect sexual function,and only a minority of patients report sexual activity.We reviewed the existing literature regarding the proportion of men who remained sexually active during and after ADT.The PubMed database was searched for studies published over the past 20 years.We selected and reviewed randomized clinical trials that provided sexual function data at baseline and during and after ADT.The primary outcome measure was the sexual function.Studies assessed sexual function using quality of life patient-reported outcome measures,which included sexual potency/activity evaluation.Information from 2947 patients was analyzed in this review.The median age of patients was 70 years.At baseline,a median of 49.9%(95%confidence interval[Cl]:49.1%-50.7%)of the patients reported being sexually active.At 6 months,12 months,and 2 years or later of ADT treatment,a median of 10.3%(95%Cl:10.2%-10.5%),8.9%(95%Cl:8.6%-9.2%),and 8.3%(95%Cl:8.2%-8.5%)of the patients reported being sexually active,respectively.Considering that half of the patients were sexually active at baseline,it seems probable that more than 10%of the patients who were sexually active before starting ADT remained sexually active when undergoing ADT.In conclusion,despite the common belief that ADT eliminates sexual activity,this analysis found that approximately 1 in 10 men are sexually active when on ADT,and this proportion is likely increased in men who are sexually active before starting ADT.Attention to sexual activity should not be dismissed in men on ADT.
文摘Objective:Current research highlights periodontal disease as a systemic inflammatory condition that may influence extra-oral diseases such as prostatic diseases,which prompted us to explore the potential association.To evaluate whether periodontal disease is associated with an increased risk of prostatic disease,including prostate cancer,benign prostatic hyperplasia(BPH),and prostatitis.Methods:A systematic search of observational studies concerning the relationship between periodontal disease and prostatic disease was performed in online databases PubMed,Embase,Web of Science,Scopus,CENTRAL,CNKI,and WanFang.Searches were conducted from database inception to 31 July 2025.Pooled hazard ratio(HR)or odds ratio(OR)with 95%confidence intervals(CIs)were synthesized.Subgroup analysis was used to detect the origin of heterogeneity,sensitivity analysis was employed to evaluate the robustness of the results,and publication bias analyses were also performed.R software was used to perform statistical analyses.Results:Sixteen studies that met the preset criteria were included in this study.In the pooled analysis,periodontal disease was associated with increased risk of prostate cancer(HR=1.23,95%CI:1.16-1.29,p<0.001)or BPH(OR=1.55,95%CI:1.41-1.70,p<0.001).Sensitivity analysis confirmed the robustness of the results.No obvious publication biaswas found in the meta-analysis.Only one cohort study reported that chronic periodontitis increases the risk of prostatitis(HR=2.521,95%CI:1.685-4.005,p<0.001).The effect of periodontal treatment on prostatic disease is still unclear.Conclusions:The systematic review and meta-analysis identified an observational association between periodontal disease and increased risks of prostate cancer and BPH.Because all included studies were observational,these results indicate association rather than causation,and further prospective and mechanistic studies are required to clarify temporality and causality.
基金supported by the National Natural Science Foundation[Grant Number:82102788]Anhui Province Key Project for Clinical Medical Research Translation and Advancement[202204295107020031,202204295107020007]Anhui Provincial University Excellent Scientific Research and Innovation Team Project[2022AH010071].
文摘Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.
文摘Background:Prostate cancer is a common malignancy,with many men on active surveillance for localized,low-risk disease also experiencing lower urinary tract symptoms(LUTS)from benign prostatic hyperplasia(BPH).Water Vapor Thermal Therapy(WVTT)is a minimally invasive BPH treatment,but its safety and efficacy in this setting are unclear.Case Description:We report three men with localized PCa on active surveillance who underwent WVTT for LUTS.Conclusions:WVTT appears safe and potentially effective in treating LUTS,especially in those with lower-risk disease and smaller prostate volumes.Further research is needed to confirm safety,efficacy,and optimal patient selection.
文摘Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advancements,transurethral approaches continue to pose risks such as urethral strictures and urinary incontinence due to mechanical and thermal stress.To address these limitations,the Suprapubic Transvesical Adenoma Resection of the Prostate(STARP)was developed,offering a direct suprapubic route that bypasses the urethra entirely.Recent studies have validated STAR-P as both feasible and safe,emphasizing advantages such as enhanced visualization of the urinary sphincter,minimized urethral trauma,effective hemostasis,and reduced operative stress.The procedure utilizes specially designed instrumentation,including a large-caliber bipolar resectoscope(42 Fr),allowing the efficient removal of substantial adenoma tissue in fewer resection passes compared to traditional methods.Objectives:This article provides a comprehensive,step-by-step description of the STAR-P technique.The primary objective is to detail patient selection criteria,preoperative assessments,procedural steps including mini-open suprapubic access,specialized instrumentation usage,resection techniques,and postoperative management protocols.Highlighting technical considerations and procedural innovations aims to inform urologists about the potential benefits of STAR-P,particularly in patients at higher risk for urethral complications or those with large prostate volumes.By documenting the procedural intricacies and outcomes clearly and thoroughly,we seek to encourage informed adoption of STAR-P as an alternative,effective surgical approach for managing benign prostatic hyperplasia,thus contributing to the evolving landscape ofminimally invasive urological surgery.
文摘Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated with dynamic real-time low-dose rate(LDR)brachytherapy using Iodine 125(I^(125)).Methods:We retrospectively reviewed 499 patients with localized prostate cancer treated with I^(125) LDR realtime brachytherapy between 2003 and 2021.The mean patient age was 65 years(range:45–84 years).Based on the National Comprehensive Cancer Network(NCCN)risk classification,230 patients(46.1%)were categorized as low risk,235(47.1%)as intermediate risk,and 34(6.8%)as high risk.Gleason scores were distributed as follows:3+3 in 283 cases(56.7%),3+4 in 157 cases(31.5%),4+3 in 46 cases(9.2%),and 4+4 in 13 cases(2.6%).The mean follow-up was 70.5 months.Results:Tumor relapse was observed in 47 patients(9.4%)over a mean follow-up period of 6.26 years(SD 4.16).Local recurrence within the prostate occurred in 20 cases(4%).Patients with nadir PSA<0.2 ng/mL at 5 years of follow-up had a significantly lower incidence of tumor recurrence(3%)compared to those with a nadir PSA>0.2 ng/mL(21.9%)(p=0.0001).Biochemical relapse-free(BRFS)rates at 5,10 and 15 years were 96%,91.5% and 88.9%,respectively.When stratified by NCCCN risk groups,5-year BRFS was 96% in low risk,98% in intermediate risk and 85% in high risk patients(p=0.003).Inmultivariate analysis,only age at the time of brachytherapy(p=0.009),initial PSA(p=0.007)and Gleason grade(p=0.007)were significantly associated with tumor recurrence.Cancer-specific survival and overall survival were 99.8% and 98.0%,respectively.Conclusions:LDR with I^(125) has excellent longterm oncological outcomes for patients with low and intermediate-risk prostate cancer,in particular,patients achieving a nadir PSA<0.2 ng/mL at 5 years post-treatment.
文摘Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.
基金supported by the Natural Science Foundation of Guangdong Province(grant number 2021A1515011485)the Traditional Chinese Medicine Multidisciplinary Innovation Team Program of Liaoning Province(grant number LNZYYCXTD-JCCX-002)+1 种基金the Key Laboratory foundation of Ministry of Education for TCM Viscera State Theory and Applications of Liaoning University of Traditional Chinese Medicine(grant number.zyzx1807)“Three levels”Talent Construction Projects in Zhuhai College of Science and Technology.
文摘Prostatic carcinoma(PCa)has become one of the most common cancers among men worldwide,with both incidence and mortality rates steadily rising.Although current treatments are effective in the early stages of PCa,many cases eventually progress to castration-resistant prostate cancer(CRPC),and led to treatment failure.To develop new therapeutic strategies to ameliorate the survival of PCa patients then has pressed the need on medicinal researchers.Of traditional Chinese medicinal herbs,Angelica gigas Naka(AGN),and its major pyranocoumarins were broadly reported on the effect of anti-PCa.However,existing reviews mainly focus on decursin(D),decursinol angelate(DA),and decursinol(DOH),without fully exploring other coumarins in AGN.Moreover,most reviews discuss general anticancer effects,with limited emphasis on PCa specifically.This review made a comprehensive summary of the coumarin components of AGN,and depicted the anti-PCa effects and mechanisms,giving a solid research support for drug discovery and development.This review also featured pharmacokinetic advantages and therapeutic potential of DOH,in order to suggest possibilities to overcome the in vivo transformation limitations of D and DA,and shed light on CRPC treatment.We also recommend future studies focus on more in vivo evidence,safety and toxicity evaluation,and clinical validation in humans.
文摘Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.
文摘Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(Grant Number 242300421283)Major Science and Technology Project of Henan Province(221100310200)。
文摘Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.
