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
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
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
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
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
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: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
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Objective To observe the clinical effects of chronic non-bacterial prostatitis treated with warm needling moxibustion. Methods One hundred and twenty-five cases were randomly divided into warm needling moxibustion gro...Objective To observe the clinical effects of chronic non-bacterial prostatitis treated with warm needling moxibustion. Methods One hundred and twenty-five cases were randomly divided into warm needling moxibustion group （42 cases）, acupuncture group （41 cases） and western medicine group （42 cases）. Of which, in warm needling moxibustion group, acupuncture combined with warming acupuncture were provided①puncture on Shènshū（肾俞 BL 23）, Gānshū （肝俞BL 18） and Zhìbiān （秩边BL 54） without retention of needles,②Guānyuán （关元CV 4）, Zhō ngjí （ 中极CV 3）, Yīnlíngquán （ 阴陵 GB 34） and Sānyīnjiāo （三阴交 SP 6） ,with warming acupuncture, once a day; in acupuncture group, the prescriptions and needling technique were the same as those in warm needling moxibustion group, without moxibustion; in western medicine group, Cernilton was applied twice a day, one pill for each time. After one course treatment, the therapeutic effects and NIH-Chronic Prostatitis Symptom Index （NIH-CPSI） of 3 groups were compared. Results The total effective rate was 88. 10% in warm needling moxibustion group, 63.41% in acupuncture group, and 66.67% in western medicine group. The clinical effect in warm needling moxibustion group was superior to that in either acupuncture group or western medicine group （both P〈0.05）. The score of NIH-CPSI was 11.92 ±7.11 in warm needling moxibustion group, 16.08±6.83 in acupuncture group, and 15.66±5.88 in western medicine group. The score of each group was obviously reduced （both P〈0.01 ） after treatments, in which, the reduction in warm needling moxibustion group was most obvious （both P〈0.0t）. Conclusion A good therapeutic effect of chronic non-bacterial prostatitis was received by warm needling moxibustion.展开更多
Aim: To assess the efficacy and safety of anal submucosal injection (ASI) of amikacin in chronic bacterial prostatitis (CBP). Methods: Fifty male outpatients with CBP were randomly divided into two groups. Thirty case...Aim: To assess the efficacy and safety of anal submucosal injection (ASI) of amikacin in chronic bacterial prostatitis (CBP). Methods: Fifty male outpatients with CBP were randomly divided into two groups. Thirty cases of ASI group were given amikacin 400 mg daily by ASI for ten times and the other twenty cases of intramuscular injection (IM) group were given the same drug dally by IM. All patients were evaluated with NIH-Chronic prostatitis symptom index (NIH-CPSI), the bacteria culture of the expressed prostate secretion (EPS), proctoscopic examination, rectal biopsy and the clinical manifestation were checked at pretreatment and on day 7 and 90 after cessation of therapy. Results: The cure rate, apparent effective rate and effective rate of ASI group and IM group were 33.3% vs 5% (P<0.05), 43.3% vs 10% (P<0.05) and 16.7% vs 20% (P>0.05), respectively. The score of NIH-CPSI in both of ASI group and IM group decreased significantly 7 days after cessation of therapy, both ASI and IM of amikacin could relieve symptoms within a short time. However, 3 months after cessation of therapy the score of NIH-CPSI in ASI group continued down in spite of no significant differences compared with 7 days after cessation of therapy, but the score of IM group was rebound nearly closed to level of pretreatment at 23.8±8.5 and significantly higher than that of ASI group. The amount of white blood cell (WBC) of EPS in ASI group increased slightly at 7 days after cessation of therapy without significant difference with pretreatment (P>0.05), but it significantly decreased at 3 months after cessation of therapy, the amount of WBC of EPS in ASI group was lower than that of IM group at 3 months after cessation of therapy (P<0.05). Proctoscopic examination of anal canal were normal after ASI therapy and the rectum biopsy showed no obvious histopathologic abnormality at the site of injection except mild focal submucosal infiltration of lymphocytes and plasma cells at 7 days after cessation of therapy which disappeared on 3 months after cessation of therapy. All patients had no evident complications. Conclusion: ASI could be recommended as a new safe, effective, painless method of antibiotics administration in the treatment of CBP.展开更多
The expressed prostatic secretions （EPSs） of men with chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS）, infertile men and normal men were subjected to microbiological study. EPSs were collected from the ...The expressed prostatic secretions （EPSs） of men with chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS）, infertile men and normal men were subjected to microbiological study. EPSs were collected from the subjects, which included 26 normal men, 11 infertile patients and 51 CP/CPPS patients. DNA was extracted from each specimen, and the V3 regions of the 16S rRNA genes were amplified using universal bacterial primers. The results showed that the EPS 16S rRNA gene-positive rate in the CP/CPPS and infertile patients was much higher than in the normal men, but without any difference among the three patient groups. The denaturing gradient gel electrophoresis （DGGE） method was used to characterize the EPS bacterial community structure of the prostate fluid from patients with CP/CPPS or infertility issues. Principal component analysis （PCA） and partial least squares （PLS） analyses of PCR-DGGE profiles revealed that the EPS bacterial community structure differed among the three groups. Three bands were identified as the key factors responsible for the discrepancy between CP/CPPS patients and infertile patients （P〈O.05）. Two bands were identified as priority factors in the discrepancy of category IliA and category IIIB prostatitis patients （P〈O.05）. According to this research, the ecological balance of the prostate and low urethra tract, when considered as a microenvironment, might play an important role in the maintenance of a healthy male reproductive tract.展开更多
We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category Ⅱ chronic bacterial prostatitis （CBP）. The aim of this study is to retrospectively compare the microbi...We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category Ⅱ chronic bacterial prostatitis （CBP）. The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin （500 rag, thrice-weekly） with a once-daily 500- or 750-mg dose of ciprofloxacin （Cipro-500 or Cipro-750 cohort, respectively）. Combined administration of azithromycin （1500 mg week^-1） with ciprofloxacin at the rate of 750 mg day^- 1 for 4 weeks rather than at 500 mg day^- 1 for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen （PSA） were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction （ED） at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation.展开更多
We studied the efficacy of culture-specific antibiotic therapy for chronic bacterial prostatitis （CBP） patients with or without prostatic calculi. This study included 101 patients （21-62 years old） who met the con...We studied the efficacy of culture-specific antibiotic therapy for chronic bacterial prostatitis （CBP） patients with or without prostatic calculi. This study included 101 patients （21-62 years old） who met the consensus criteria for CBP （National Institutes of Health category II）. According to the results of transrectal ultrasonography （TRUS）, all patients were divided into two groups： Group 1, CBP with prostatic calculi, n=39; Group 2, CBP without prostatic calculi, n=62. All patients received optimal antimicrobial therapy for 4 weeks and followed up for a minimum of 3 months （range： 3-8 months）. In addition to expressed prostatic secretions （EPS） and urine culture, all patients were asked to complete the National Institutes of Health Chronic Prostatitis Symptom Index （NIH-CPSI） and the subjective global assessment （SGA）. The microbiological eradication rate at the end of treatment were 32/39 （82.1%） and 54/62 （87.1%）, while the rates for continued eradication at the end of study were 17/39 （43.6%） and 45/62 （72.6%） in Group I and Group 2 （P〈0.01）, respectively. We observed a decrease in the total NIH-CPSI score median values from 24 to 19 in Group I and from 24 to 11 in Group 2. The pain subscore （P〈0.01）, urinary sunscore （P〈0.05） and quality of life （QoL; P〈0.05） as well as the total NIH-CPSI score （P〈0.01） were significantly improved after antimicrobial treatment in Group 2 compared to Group 1. Response, defined as a decrease of the NI H-CPSI total score by at least 50%, was seen in Group I versusGroup 2 in 38.5% and 58.1% （P〈0.01）, respectively. Our results showed that prostatic calculi influence the antimicrobial efficacy in men with CBP, There was a noticeable decrease in the cure rate of CBP patients with prostatic calculi due to relapse after antimicrobial therapy.展开更多
The combination of levofloxacin and a1 adrenergic antagonist treatment is the current preferred choice for both bacterial and non-bacterial prostatitis. The aim of this study is to explore the influence of a1 adrenerg...The combination of levofloxacin and a1 adrenergic antagonist treatment is the current preferred choice for both bacterial and non-bacterial prostatitis. The aim of this study is to explore the influence of a1 adrenergic antagonists on the pharmacokinetics of levofloxacin using rat models with acute bacterial prostatitis （ABP） induced by direct injection with Escherichia coil （ATCC25922）, A total of 96 model rats were randomly assigned into two groups： the experimental group （treated with both tamsulosin and levofloxacin, n=48） and the control group （treated with levofloxacin and solvents, n=48）. Six rats from each group were euthanized to collect blood, liver, kidney and prostate samples at the time points of 0. 125, 0.25, 0.5, 1,2, 4, 8 and 12 h after drug administration. The levofloxacin concentrations were detected by high performance liquid chromatography （HPLC）, and the pharmacokinetic parameters were calculated using the 3p97 software program. There were no obvious differences （P〉0.05） between the experimental and control groups in the major pharmacokinetic parameters of levofloxacin, including the halftime （t1/2）, time to peak （tpeak）, clearance rate （CL）, maximum concentration （Cmax） and area under the curve （AUC0-12）, in the plasma or in the hepatic and kidney tissues of the model rats. However, in the prostatic tissues, tamsulosin increased the Cmax, prolonged the t1/2 and decreased the CL of levofloxacin （P〈0.05）. These results indicate that tamsulosin may enhance the effect of levofloxacin in the treatment of bacterial prostatitis without changing the drug concentration in the liver and kidney.展开更多
The urinary, psychosocial, organ-specific, infection, neurological/systemic and tenderness （UPOINT） phenotype system has been validated to be an effective phenotype system in classifying patients with chronic prosta...The urinary, psychosocial, organ-specific, infection, neurological/systemic and tenderness （UPOINT） phenotype system has been validated to be an effective phenotype system in classifying patients with chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS） in western populations. To validate the utility of the UPOINT system and evaluate the effect of multimodal therapy based on the UPOINT system in Chinese patients with CPICPPS, we performed this study. Chinese patients with CP/CPPS were prospectively offered multimodal therapy using the UPOINT system and re-examined after 6 months. A minimum 6-point drop in National Institutes of Health-Chronic Prostatitis Symptoms Index （NIH-CPSI） was set to be the primary endpoint. Finally, 140 patients were enrolled in the study. The percentage of patients with each domain was 59.3%, 45.0%, 49.3%, 22.1%, 37.9%, and 56.4% for the UPOINT, respectively. The number of positive domains significantly correlated with symptom severity, which is measured by total NIH-CPSI scores （r = 0.796, P 〈 0.001）. Symptom duration was associated with a greater number of positive domains （r = 0.589, P〈 0.001）. With 6 months follow-up at least, 75.0% （105/140） had at least a 6-point improvement in NIH-CPSI after taking the therapy. All NIH-CPSI scores were significantly improved from original ones： pain 10.14 ± 4.26 to 6.60 ± 3.39, urinary 6.29 ± 2.42 to 3.63 ± 1.52, quality of life 6.56 ± 2.44 to 4.06 ± 1.98, and total 22.99 ± 7.28 to 14.29 ±5.70 （all P〈 0.0001）. Our study indicates that the UPOINT system is clinically feasible in classifying Chinese patients with CP/CPPS and directing therapy.展开更多
Levofloxacin is a synthetic fluoroquinolone that is usually used to treat chronic bacterial prostatitis. We investigated the safety and efficacy of levofloxacin compared with ciprofloxacin for the treatment of chronic...Levofloxacin is a synthetic fluoroquinolone that is usually used to treat chronic bacterial prostatitis. We investigated the safety and efficacy of levofloxacin compared with ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients. This was a multicenter, open-label, randomized controlled non-inferiority trial. Four hundred and seventy-one patients with clinical symptoms/ signs were enrolled into the study, and 408 patients were microbiologically confirmed chronic bacterial prostatitis, who were randomized to either oral levofloxacin （500 mg q,d.） or ciprofloxacin （500 mg b.i^d.） for 4 weeks. Bacterial clearance rate, clinical symptoms/signs, adverse reactions and disease recurrence were assessed. The clinical symptoms and signs （including dysuria, perineal discomfort or pain） and bacteria cultures in 209 patients treated with levofloxacin and 199 patients treated with ciprofloxacin were similar. The most common bacteria were Escherichia cofiand Staphylococcus aureus. One to four weeks after the end of 4 weeks treatment, the bacterial clearance rate （86.06% vs. 60.03%; P〈O.05） and the clinical efficacy （including clinical cure and clinical improvement（93.30% vs. 71.86%; P〈0.05）） were significantly higher in the levofloxacin-treated group than in the ciprofloxacin-treated group. The microbiological recurrence rate was significantly lower in the levofloxacin-treated group than in the ciprofloxacin-treated group （4.00% vs. 19.25%; P〈0.05）. Rates of adverse events and treatment-related adverse events were slightly lower in the levofloxacin-treated group than in ciprofloxacin-treated group. Levofloxacin showed some advantages over ciprofloxacin in terms of clinical efficacy and disease recurrence, with a low rate of adverse events, for the treatment of chronic bacterial prostatitis in Chinese patients.展开更多
This study aims to validate our hypothesis that acid-sensing ion channels （ASICs） may contribute to the symptom of pain in patients with chronic prostatitis （CP）. We first established a CP rat model, then isolated...This study aims to validate our hypothesis that acid-sensing ion channels （ASICs） may contribute to the symptom of pain in patients with chronic prostatitis （CP）. We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASICla was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASICla on the Ca2＋ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium （[Ca~＊]i） intensity. The effect of ASICla on the p38/mitogen-activated protein kinase （MAPK） signaling pathway was also determined. ASICla was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASICla expression increased [Ca2＋]i intensity in the dorsal horn neurons of rat spinal cord. ASICla also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASICla knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.展开更多
We compared the potential phenotypic properties of coryneform bacteria associated with chronic prostatitis syndrome （CPS）, such as secretory inhibitor of lysozyme （SIL） and secretory inhibitor of platelet microbic...We compared the potential phenotypic properties of coryneform bacteria associated with chronic prostatitis syndrome （CPS）, such as secretory inhibitor of lysozyme （SIL） and secretory inhibitor of platelet microbicidal protein （SIPMP）. A total of 110 clinical isolates of coryneform bacteria isolated from the seminal fluid of healthy men and men with CPS were tested. SIPMP production was tested by inhibiting platelet microbicidal protein （PMP） bioactivity against Bacillus subtilis, and was expressed as percentage of inhibition of PMP bactericidal activity. SIL production was tested by inhibiting lysozyme activity against Micrococcus lysodeikticus and was expressed in microgram per millilitre of inactivated lysozyme. A significantly higher proportion of CPS strains （58.7% vs. 19.2 %） was SIPMP-positive compared with non-CPS strains （P 〈 0.01）. Of the CPS strains tested, 77.8% were SIL-positive compared with 34% of the non- CPS isolates （P 〈 0.05）. These results suggest that the diagnosis of CPS should not rely solely on classical parameters, for example, the identification and counting of microorganisms, but the functional significance of these parameters must be estimated, possibly by the concentration of different bacterial substrains, detection of opportunistic microorganisms with pathogenic properties, such as pronounced resistance to the cationic antimicrobial peptides, and/or the ability to inhibit the antimicrobial host defence factors.展开更多
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.
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.
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.
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 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supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
文摘Objective To observe the clinical effects of chronic non-bacterial prostatitis treated with warm needling moxibustion. Methods One hundred and twenty-five cases were randomly divided into warm needling moxibustion group （42 cases）, acupuncture group （41 cases） and western medicine group （42 cases）. Of which, in warm needling moxibustion group, acupuncture combined with warming acupuncture were provided①puncture on Shènshū（肾俞 BL 23）, Gānshū （肝俞BL 18） and Zhìbiān （秩边BL 54） without retention of needles,②Guānyuán （关元CV 4）, Zhō ngjí （ 中极CV 3）, Yīnlíngquán （ 阴陵 GB 34） and Sānyīnjiāo （三阴交 SP 6） ,with warming acupuncture, once a day; in acupuncture group, the prescriptions and needling technique were the same as those in warm needling moxibustion group, without moxibustion; in western medicine group, Cernilton was applied twice a day, one pill for each time. After one course treatment, the therapeutic effects and NIH-Chronic Prostatitis Symptom Index （NIH-CPSI） of 3 groups were compared. Results The total effective rate was 88. 10% in warm needling moxibustion group, 63.41% in acupuncture group, and 66.67% in western medicine group. The clinical effect in warm needling moxibustion group was superior to that in either acupuncture group or western medicine group （both P〈0.05）. The score of NIH-CPSI was 11.92 ±7.11 in warm needling moxibustion group, 16.08±6.83 in acupuncture group, and 15.66±5.88 in western medicine group. The score of each group was obviously reduced （both P〈0.01 ） after treatments, in which, the reduction in warm needling moxibustion group was most obvious （both P〈0.0t）. Conclusion A good therapeutic effect of chronic non-bacterial prostatitis was received by warm needling moxibustion.
文摘Aim: To assess the efficacy and safety of anal submucosal injection (ASI) of amikacin in chronic bacterial prostatitis (CBP). Methods: Fifty male outpatients with CBP were randomly divided into two groups. Thirty cases of ASI group were given amikacin 400 mg daily by ASI for ten times and the other twenty cases of intramuscular injection (IM) group were given the same drug dally by IM. All patients were evaluated with NIH-Chronic prostatitis symptom index (NIH-CPSI), the bacteria culture of the expressed prostate secretion (EPS), proctoscopic examination, rectal biopsy and the clinical manifestation were checked at pretreatment and on day 7 and 90 after cessation of therapy. Results: The cure rate, apparent effective rate and effective rate of ASI group and IM group were 33.3% vs 5% (P<0.05), 43.3% vs 10% (P<0.05) and 16.7% vs 20% (P>0.05), respectively. The score of NIH-CPSI in both of ASI group and IM group decreased significantly 7 days after cessation of therapy, both ASI and IM of amikacin could relieve symptoms within a short time. However, 3 months after cessation of therapy the score of NIH-CPSI in ASI group continued down in spite of no significant differences compared with 7 days after cessation of therapy, but the score of IM group was rebound nearly closed to level of pretreatment at 23.8±8.5 and significantly higher than that of ASI group. The amount of white blood cell (WBC) of EPS in ASI group increased slightly at 7 days after cessation of therapy without significant difference with pretreatment (P>0.05), but it significantly decreased at 3 months after cessation of therapy, the amount of WBC of EPS in ASI group was lower than that of IM group at 3 months after cessation of therapy (P<0.05). Proctoscopic examination of anal canal were normal after ASI therapy and the rectum biopsy showed no obvious histopathologic abnormality at the site of injection except mild focal submucosal infiltration of lymphocytes and plasma cells at 7 days after cessation of therapy which disappeared on 3 months after cessation of therapy. All patients had no evident complications. Conclusion: ASI could be recommended as a new safe, effective, painless method of antibiotics administration in the treatment of CBP.
文摘The expressed prostatic secretions （EPSs） of men with chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS）, infertile men and normal men were subjected to microbiological study. EPSs were collected from the subjects, which included 26 normal men, 11 infertile patients and 51 CP/CPPS patients. DNA was extracted from each specimen, and the V3 regions of the 16S rRNA genes were amplified using universal bacterial primers. The results showed that the EPS 16S rRNA gene-positive rate in the CP/CPPS and infertile patients was much higher than in the normal men, but without any difference among the three patient groups. The denaturing gradient gel electrophoresis （DGGE） method was used to characterize the EPS bacterial community structure of the prostate fluid from patients with CP/CPPS or infertility issues. Principal component analysis （PCA） and partial least squares （PLS） analyses of PCR-DGGE profiles revealed that the EPS bacterial community structure differed among the three groups. Three bands were identified as the key factors responsible for the discrepancy between CP/CPPS patients and infertile patients （P〈O.05）. Two bands were identified as priority factors in the discrepancy of category IliA and category IIIB prostatitis patients （P〈O.05）. According to this research, the ecological balance of the prostate and low urethra tract, when considered as a microenvironment, might play an important role in the maintenance of a healthy male reproductive tract.
文摘We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category Ⅱ chronic bacterial prostatitis （CBP）. The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin （500 rag, thrice-weekly） with a once-daily 500- or 750-mg dose of ciprofloxacin （Cipro-500 or Cipro-750 cohort, respectively）. Combined administration of azithromycin （1500 mg week^-1） with ciprofloxacin at the rate of 750 mg day^- 1 for 4 weeks rather than at 500 mg day^- 1 for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen （PSA） were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction （ED） at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation.
文摘We studied the efficacy of culture-specific antibiotic therapy for chronic bacterial prostatitis （CBP） patients with or without prostatic calculi. This study included 101 patients （21-62 years old） who met the consensus criteria for CBP （National Institutes of Health category II）. According to the results of transrectal ultrasonography （TRUS）, all patients were divided into two groups： Group 1, CBP with prostatic calculi, n=39; Group 2, CBP without prostatic calculi, n=62. All patients received optimal antimicrobial therapy for 4 weeks and followed up for a minimum of 3 months （range： 3-8 months）. In addition to expressed prostatic secretions （EPS） and urine culture, all patients were asked to complete the National Institutes of Health Chronic Prostatitis Symptom Index （NIH-CPSI） and the subjective global assessment （SGA）. The microbiological eradication rate at the end of treatment were 32/39 （82.1%） and 54/62 （87.1%）, while the rates for continued eradication at the end of study were 17/39 （43.6%） and 45/62 （72.6%） in Group I and Group 2 （P〈0.01）, respectively. We observed a decrease in the total NIH-CPSI score median values from 24 to 19 in Group I and from 24 to 11 in Group 2. The pain subscore （P〈0.01）, urinary sunscore （P〈0.05） and quality of life （QoL; P〈0.05） as well as the total NIH-CPSI score （P〈0.01） were significantly improved after antimicrobial treatment in Group 2 compared to Group 1. Response, defined as a decrease of the NI H-CPSI total score by at least 50%, was seen in Group I versusGroup 2 in 38.5% and 58.1% （P〈0.01）, respectively. Our results showed that prostatic calculi influence the antimicrobial efficacy in men with CBP, There was a noticeable decrease in the cure rate of CBP patients with prostatic calculi due to relapse after antimicrobial therapy.
文摘The combination of levofloxacin and a1 adrenergic antagonist treatment is the current preferred choice for both bacterial and non-bacterial prostatitis. The aim of this study is to explore the influence of a1 adrenergic antagonists on the pharmacokinetics of levofloxacin using rat models with acute bacterial prostatitis （ABP） induced by direct injection with Escherichia coil （ATCC25922）, A total of 96 model rats were randomly assigned into two groups： the experimental group （treated with both tamsulosin and levofloxacin, n=48） and the control group （treated with levofloxacin and solvents, n=48）. Six rats from each group were euthanized to collect blood, liver, kidney and prostate samples at the time points of 0. 125, 0.25, 0.5, 1,2, 4, 8 and 12 h after drug administration. The levofloxacin concentrations were detected by high performance liquid chromatography （HPLC）, and the pharmacokinetic parameters were calculated using the 3p97 software program. There were no obvious differences （P〉0.05） between the experimental and control groups in the major pharmacokinetic parameters of levofloxacin, including the halftime （t1/2）, time to peak （tpeak）, clearance rate （CL）, maximum concentration （Cmax） and area under the curve （AUC0-12）, in the plasma or in the hepatic and kidney tissues of the model rats. However, in the prostatic tissues, tamsulosin increased the Cmax, prolonged the t1/2 and decreased the CL of levofloxacin （P〈0.05）. These results indicate that tamsulosin may enhance the effect of levofloxacin in the treatment of bacterial prostatitis without changing the drug concentration in the liver and kidney.
文摘The urinary, psychosocial, organ-specific, infection, neurological/systemic and tenderness （UPOINT） phenotype system has been validated to be an effective phenotype system in classifying patients with chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS） in western populations. To validate the utility of the UPOINT system and evaluate the effect of multimodal therapy based on the UPOINT system in Chinese patients with CPICPPS, we performed this study. Chinese patients with CP/CPPS were prospectively offered multimodal therapy using the UPOINT system and re-examined after 6 months. A minimum 6-point drop in National Institutes of Health-Chronic Prostatitis Symptoms Index （NIH-CPSI） was set to be the primary endpoint. Finally, 140 patients were enrolled in the study. The percentage of patients with each domain was 59.3%, 45.0%, 49.3%, 22.1%, 37.9%, and 56.4% for the UPOINT, respectively. The number of positive domains significantly correlated with symptom severity, which is measured by total NIH-CPSI scores （r = 0.796, P 〈 0.001）. Symptom duration was associated with a greater number of positive domains （r = 0.589, P〈 0.001）. With 6 months follow-up at least, 75.0% （105/140） had at least a 6-point improvement in NIH-CPSI after taking the therapy. All NIH-CPSI scores were significantly improved from original ones： pain 10.14 ± 4.26 to 6.60 ± 3.39, urinary 6.29 ± 2.42 to 3.63 ± 1.52, quality of life 6.56 ± 2.44 to 4.06 ± 1.98, and total 22.99 ± 7.28 to 14.29 ±5.70 （all P〈 0.0001）. Our study indicates that the UPOINT system is clinically feasible in classifying Chinese patients with CP/CPPS and directing therapy.
文摘Levofloxacin is a synthetic fluoroquinolone that is usually used to treat chronic bacterial prostatitis. We investigated the safety and efficacy of levofloxacin compared with ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients. This was a multicenter, open-label, randomized controlled non-inferiority trial. Four hundred and seventy-one patients with clinical symptoms/ signs were enrolled into the study, and 408 patients were microbiologically confirmed chronic bacterial prostatitis, who were randomized to either oral levofloxacin （500 mg q,d.） or ciprofloxacin （500 mg b.i^d.） for 4 weeks. Bacterial clearance rate, clinical symptoms/signs, adverse reactions and disease recurrence were assessed. The clinical symptoms and signs （including dysuria, perineal discomfort or pain） and bacteria cultures in 209 patients treated with levofloxacin and 199 patients treated with ciprofloxacin were similar. The most common bacteria were Escherichia cofiand Staphylococcus aureus. One to four weeks after the end of 4 weeks treatment, the bacterial clearance rate （86.06% vs. 60.03%; P〈O.05） and the clinical efficacy （including clinical cure and clinical improvement（93.30% vs. 71.86%; P〈0.05）） were significantly higher in the levofloxacin-treated group than in the ciprofloxacin-treated group. The microbiological recurrence rate was significantly lower in the levofloxacin-treated group than in the ciprofloxacin-treated group （4.00% vs. 19.25%; P〈0.05）. Rates of adverse events and treatment-related adverse events were slightly lower in the levofloxacin-treated group than in ciprofloxacin-treated group. Levofloxacin showed some advantages over ciprofloxacin in terms of clinical efficacy and disease recurrence, with a low rate of adverse events, for the treatment of chronic bacterial prostatitis in Chinese patients.
基金This research was supported in part by grants from the National Natural Science Foundation of China （No. 81400757） National College Students Innovation and Entrepreneurship Training Program （No. 201510366009） and Anhui Provincial Natural Science Foundation （1508085QH 171 ）.
文摘This study aims to validate our hypothesis that acid-sensing ion channels （ASICs） may contribute to the symptom of pain in patients with chronic prostatitis （CP）. We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASICla was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASICla on the Ca2＋ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium （[Ca~＊]i） intensity. The effect of ASICla on the p38/mitogen-activated protein kinase （MAPK） signaling pathway was also determined. ASICla was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASICla expression increased [Ca2＋]i intensity in the dorsal horn neurons of rat spinal cord. ASICla also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASICla knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.
文摘We compared the potential phenotypic properties of coryneform bacteria associated with chronic prostatitis syndrome （CPS）, such as secretory inhibitor of lysozyme （SIL） and secretory inhibitor of platelet microbicidal protein （SIPMP）. A total of 110 clinical isolates of coryneform bacteria isolated from the seminal fluid of healthy men and men with CPS were tested. SIPMP production was tested by inhibiting platelet microbicidal protein （PMP） bioactivity against Bacillus subtilis, and was expressed as percentage of inhibition of PMP bactericidal activity. SIL production was tested by inhibiting lysozyme activity against Micrococcus lysodeikticus and was expressed in microgram per millilitre of inactivated lysozyme. A significantly higher proportion of CPS strains （58.7% vs. 19.2 %） was SIPMP-positive compared with non-CPS strains （P 〈 0.01）. Of the CPS strains tested, 77.8% were SIL-positive compared with 34% of the non- CPS isolates （P 〈 0.05）. These results suggest that the diagnosis of CPS should not rely solely on classical parameters, for example, the identification and counting of microorganisms, but the functional significance of these parameters must be estimated, possibly by the concentration of different bacterial substrains, detection of opportunistic microorganisms with pathogenic properties, such as pronounced resistance to the cationic antimicrobial peptides, and/or the ability to inhibit the antimicrobial host defence factors.
