1.Mechanism of the regulation of prostate cancer stem cells by CAF:Based on the Wnt/β-catenin and SDF-1/CXCR4 pathways
Haoran CHEN ; Xudong ZHU ; Jiazheng WANG ; Yafei CHEN ; Yilin WANG ; Hao LIU
National Journal of Andrology 2025;31(10):867-873
Objective To investigate the mechanism by which cancer-associated fibroblast(CAF)in the tumor microenvironment regulate key pathways in prostate cancer stem cells(PCSCs).Methods An in vitro co-culture system of CAF and PCSC was established to observe the effects of CAF on PCSC proliferation and sphere formation.Prostate cancer stem cells were treated with CAF conditioned medium pre-treated with Wnt inhibitor DKK-1 and SDF-1 neutralizing anti-body(MAB310).Western blot was used to detect the expression of β-catenin,CXCR4,CD133 and CD44 in PCSCs.And PCR was used to detect the expression of β-catenin,CXCR4,TCF,and LEF mRNA.TOPflash/FOPflash dual-luciferase reporter assays were conducted to detect the effects of SDF-1 on Wnt/β-catenin signaling activity in PCSCs.Results ELISA results showed that the secretion of Wnt3a and SDF-1 in CAF supernatant was significantly higher than that in WPMY-1 cells(P<0.05).The A value of PCSCs co-cultured with CAF at a 1∶6 ratio was significantly higher than that of the PCSC-only group(P<0.0 1),and CAF promoted sphere formation in PCSCs(P<0.05).Western blot results showed that CAF-CM significantly increased the relative expression of β-catenin,CXCR4,CD133 and CD44 in PCSCs(P<0.01).Compared to CAF-CM,CAFanti-Wnt-CM significantly reduced the expression of β-catenin,CD133 and CD44(P<0.01).CAFanti-SDF-1-CM also significantly inhibited the expression of CXCR4,β-catenin,CD133 and CD44(P<0.01).PCR results showed that CAFanti-SDF-1-CM inhibited the expression of β-catenin,CXCR4 and downstream Wnt signaling effectors TCF and LEF(P<0.01).Dual-luciferase reporter assay results showed that luciferase activity in the CAFanti-SDF-1-CM group was significantly lower than that in the CAF-CM group(P<0.05).Conclusion CAF reg-ulates the stemness of PCSCs through the Wnt/β-catenin and SDF-1/CXCR4 pathways.CXCR4 may enhance the mainte-nance of stemness by activating β-catenin.
2.Construction of a high-efficiency risk-prediction model for urinary tract infection after BPH surgery based on machine learning algorithm
Guiping FU ; Xiao LIU ; Zhengdong HONG ; Dongping ZHOU
National Journal of Andrology 2025;31(10):874-880
Objective To explore the risk factors for urinary tract infection(UTI)after benign prostatic hyperpla-sia(BPH)surgery,and construct a high-efficiency risk-prediction model based on machine learning algorithms(MLA).Methods This retrospective study included 200 cases of BPH surgically treated in Xinyu Hospital of Traditional Chinese Medicine from May 2020 to April 2023.Twenty-three cases were included in the UTI group,and 177 were enrolled into the non-UTI group.The relevant data were collected and analyzed for the statistically significant factors by univariate logistic analysis by using the SPSS software,MLA-based logistic regression,back-propagation(BP)neural networks and decision classification and regression tree(CRT).And the predictive values of the models established via different algorithms using the area under the receiver operating characteristic curve(AUC)were compared.We assessed the prediction accuracy of the models and identified one with the best prediction efficiency based on the mean absolute error(MAE).Results Univariate analysis indicated statisti-cally significant differences between the UTI and non-UTI groups in age,comorbid diabetes mellitus(DM),urinary catheter-in-dwelling time,prostate volume,preoperative catheterization,preoperative IPSS(P<0.05).The independent predictive varia-bles for UTI after BPH surgery were shown to be age,IPSS,comorbid DM and prostate volume by the method of multivariate lo-gistic regression model(P<0.05).Age,urinary catheter-indwelling time,prostate volume and IPSS were assessed as the influ-ence factors by the CRT model(P<0.05),and prostate volume,IPSS,age and urinary catheter-indwelling time were assessed as the influence factors by the BP neural network model(P<0.05).Among the 3 risk-prediction models,the one constructed with the BP neural networks exhibited the best prediction efficiency(AUC:0.992,the optimal truncation value:0.912,corre-sponding sensitivity and specificity:0.957 and 0.955).Conclusion The risk-prediction model constructed by MLA and BP neural networks based on the characteristic factors of age,preoperative urinary retention catheterization,urinary catheter-indwell-ing time,IPSS and comorbid DM has a high predictive value for UTI after BPH surgery which can be applied to the identification and management of such high-risk population.
3.Correlation between Gleason grade and free prostate-specific antigen,serum ferritin and uric acid levels in patients with prostate cancer
Haocheng ZHANG ; Meimei TAO ; Jiong ZHANG ; Yuhang QIAN ; Chunmei LIAO ; Peng WANG ; Genqiang LANG ; Lin LI ; Xiaojun DENG
National Journal of Andrology 2025;31(10):881-884
Objective To discuss the correlation between free prostate specific antigen(fPSA),serum ferritin(SF),blood uric acid(SUA)levels and Gleason grading in patients with prostate cancer(PCa).Methods The clinical data of 61 patients with prostate biopsy treated in 411 Hospital of Shanghai University from January to December of 2023 were retrospectively analyzed.According to the results of puncture,the patients were divided into benign prostatic hyperpla-sia(BPH)group(31 cases)and PCa group(30 cases).The levels of fPSA,SF and SUA in patients and Gleason grade in biopsy cases were analyzed.The correlation between fPSA,SF and SUA levels and Gleason grade was analyzed by the method of Spearman.And the diagnostic efficacy of fPSA,SF and SUA levels on PCa was analyzed by receiver operating characteristic curve(ROC).Results The levels of fPSA,SF and SUA in PCa group were significantly higher than those in BPH group(P<0.05).There were statistically significant differences in levels of fPSA SF and SUA in PCA patients with different Gleason grades(P<0.05).With the specificity reaching 96.08%and sensitivity reaching 94.35%,the ar-ea under the curve(AUC)of the combined fPSA,SF and SUA levels in the diagnosis of PCa was 0.982,which was higher than that of the single fPSA,SF and SUA levels(P<0.05).SF and SUA levels in PCa patients were positively correlated with Gleason grade(P<0.05),while fPSA levels were not correlated with Gleason grade(P>0.05).Conclusion The levels of SF and SUA in PCa patients are positively correlated with Gleason grade,which can be used as an important index to predict Gleason grade in PCa patients.
4.Causal relationship between periodontal disease and prostate cancer:A two-sample bidirectional Mendelian randomization analysis in two races
Xiaoxu JIN ; Jing LIU ; Xiaodong ZHAO ; Wenyi HUANG ; Ning DONG ; Shihao WANG ; Mengfei MA ; Yulin ZHOU ; Yuhao CHEN ; Jinlu SUN ; Jie DONG ; Jun HU ; Song XU
National Journal of Andrology 2025;31(10):885-890
Objective The aim of this study is to discuss the causal relationship between periodontal disease(PD)and prostate cancer(PCa).Methods A two-sample bidirectional Mendelian randomization(MR)analysis based on publicly statistical data from genome-wide association studies(GWAS)was conducted.MR Egger,weighted medium,simple mode and weighted mode were supplemented,while inverse variance weighted analysis(IVW)was the main method of analysis.Heterogeneity testing,pleiotropy testing and leave-one-out testing were used to assess the sensitivity and stabili-ty.Results The results of MR analysis showed that PD had no significant impact on the occurrence of PCa:East Asian(IVW,PD:OR=1.07,P=0.48);European(IVW,PD:OR=1.00,P=0.37,periodontitis:OR=1.03,P=0.14,chronic gingivitis:OR=0.99,P=0.37,chronic periodontitis:OR=1.03,P=0.22).The reverse MR analysis also did not show a causal relationship between PCa and PD:East Asian(IVW,PD:OR=0.97,P=0.22);European(IVW,PD:OR=0.84,P=0.44,periodontitis:OR=1.01,P=0.75,chronic gingivitis:OR=0.93,P=0.23,chronic periodontitis:OR=0.99,P=0.80).The results of other analysis were consistent with those of IVW analysis.Conclusions The results of our two-sample bidirectional MR analysis do not support a causal relationship between PD and PCa.
5.Effect of bladder neck preservation during transurethral thulium laser enucleation of the prostate on stress urinary incontinence and retrograde ejaculation
Qi ZHANG ; Guobin WENG ; Xuping YAO ; Gang WANG ; Jianjun HUANG
National Journal of Andrology 2025;31(10):891-896
Objective To evaluate the effects of bladder neck preservation on postoperative stress urinary inconti-nence and retrograde ejaculation in patients undergoing transurethral thulium laser enucleation of the prostate(ThuLEP).Methods The clinical data of 203 patients who underwent ThuLEP in our hospital from September 2021 to December 2023 were retrospectively analyzed.According to the operation method,the patients were divided into bladder neck preservation group(n=95)and non-bladder neck preservation group(n=108).The occurrence of postoperative stress urinary inconti-nence and retrograde ejaculation of the two groups were compared.Results The differences between the patients of two groups in operative time(110[80,130]min vs 110[90,140]min),hospital stay(8[8,8]d vs 8[8,8]d),in-dwelling catheter time(7[7,7]h vs 7[7,7]h),and hemoglobin decline(9[6,14]g/L vs 8[4,13]g/L)were not statistically significant(P>0.05).There were no statistically significant differences between the two groups at 3 months postoperatively in maximum flow rate(20[18,21]mL/s vs 19[18,20]mL/s),scores of International Prostate Symp-tom Scale(5[4,6]vs 5[4,5]),post-void residual urine volume(0[0,8]mL vs 0[0,7.5]mL)and quality of life(2[1,3]vs 2[1,3])(P>0.05).The differences in the rates of postoperative stress urinary incontinence(2.1%vs 9.3%)and retrograde ejaculation(49.4%vs 74.5%)between the two groups were statistically significant(P<0.05).Conclusion Bladder neck preservation during ThuLEP reduces the incidence of postoperative stress urinary incontinence and retrograde ejaculation.
6.Effects of tri(2-chloroethyl)phosphate on reproductive function of male mice:Based on non-targeted metabolomics
Yang XU ; Yaofu LIN ; Wen LI ; Baohao LIU ; Guanjun LÜ ; Baosong WANG ; Jing LIU
National Journal of Andrology 2025;31(10):897-903
Objective To investigate the effects of organophosphate flame retardant tri(2-chloroethyl)phosphate(TCPP)on reproductive function in male mice by the approach of non-targeted metabolomics.Methods A total of twelve 6-week-old SPF male CD-1 mice were randomly divided into control group and TCPP group,with 6 mice in each group.TCPP group was given TCPP(at the dose of 100 mg/kg/d)intragastrically,and control group was intragastrically adminis-trated with the same amount of corn oil(solvent control).After 6 weeks,the mice were killed,and the sperm were isolated from the epididymis.The sperm concentration and viability were analyzed.Testicular tissue sections were stained with he-matoxylin,and ki67 expression was detected by immunohistochemistry.Non-targeted metabolomics was used to detect the difference of metabolites in testicular tissue between the two groups,and to analyze the difference of metabolites and related pathway changes between the two groups.Results Compared with control group,the total sperm motility of mice in TCPP treatment group was significantly decreased(P<0.05).HE staining showed irregular arrangement of spermatogenic tubule supporting cell layer in TCPP treatment group.The expression level of ki67 in testicular tissue of mice treated with TCPP was significantly decreased(P<0.05).Non-targeted metabolomics detected 266 up-regulated metabolites with statistical difference.And 554 down-regulated metabolites with statistical difference,among which the largest difference multiples were organic acids and amino acid metabolites.The pathways with the highest concentration of differential metabolites in-cluded purine metabolism,nucleotide metabolism,amino acid metabolism,cofactor synthesis,etc.,which were mainly re-lated to basic cell life activities,pathophysiology and chemical carcinogenesis.Conclusion TCPP can significantly re-duce sperm motility and ki67 expression in mice at the dosage of 100 mg/kg/d,which might be related to its influence on key metabolic pathways such as purine,amino acid and pyruvate.
7.A multicenter retrospective histopathological analysis of testicular torsion-related orchiectomy specimens
Guoxiong LUO ; Qinjun SU ; Qiang ZHAO ; Donghong LIU ; Yajun XU ; Linling LIU ; Bin ZHANG ; Yindong KANG ; Dehui CHANG
National Journal of Andrology 2025;31(10):904-908
Objective This study aims to explore the correlation between the grade of testicular tissue damage and clinical features which is used to evaluate the viability of testicular tissue after the orchidopexy for testicular torsion.Methods We conducted a retrospective,multicenter analysis of pathological specimens obtained from patients who under-went unilateral orchiectomy due to testicular torsion.Tissue viability was reassessed by the Mikuz grading scale.The corre-lations among tissue viability,duration of torsion symptoms,the angle of torsion,preoperative Doppler ultrasound image and intraoperative testicular resuscitation methods were analyzed.Results Eighty-five pathological specimens were en-rolled from 4 medical centers.The age range was 18 years(IQR 14-33),with a median torsion angle of 480°(IQR 180°-1080°).The interval from the torsion onset to surgical intervention was 18 hours(IQR 9-84).In the subgroup analysis of different torsion durations,the distribution of Grade I injuries was as follows.The subgroup within 12 hours ac-counted for 37.5%.The subgroup between 12 to 24 hours accounted for 14.28%.And the subgroup between 24 to 48 hours ac-counted for 6.45%.The subgroup exceeding 48 hours only accounted for 3.13%.Four patients received orchiectomy due to pre-operative ultrasound image indicating necrosis,correlating with Mikuz grade 3 tissue damage.The decision was made based on the failure of color recovery of affected testis in 57 cases,revealing 12.28%with grade 1 and 35.89%with grade Ⅱ damage.Twenty-four cases were identified as an Arda score of 3,with 4.16%showing grade 1 and 20.83%showing grade Ⅱ Mikuz damage.The method of Arda's grading could be used to determine the vitality of testicular tissue more accurately compared to the post-resusci-tation color observation method(P=0.032).Conclusion Pathological reassessment provides a precise determination of tis-sue viability in the affected testis.In some instances,the testicular tissue damage can be found potentially reversible.
8.Clinical and imaging characteristics of granulomatous prostatitis:Report of 13 cases
Jinkai DONG ; Baobo ZHAO ; Shidong ZUO ; Lingsheng KONG ; Chenwei FU ; Xuechao LI ; Lijun CHEN
National Journal of Andrology 2025;31(10):909-914
Objective The aim of this study is to retrospectively analyze the clinical and imaging characteristics,treatment and prognosis of 13 patients with granulomatous prostatitis(GP),and to provide reference for the diagnosis and treatment for GP.Methods The clinical information of 13 GP patients extracted from electronic medical records including demographic characteristic risk factors,clinical symptoms,laboratory findings,imaging findings(ultrasound,CT,MRI,FDG-PET-CT),treatment and outcomes were analyzed retrospectively from January 2018 to August 2023 at our center.Results The average age of 13 patients with GP was(65.69±6.46)years.And the average score of IPSS was(23.40±5.8).Five patients appeared positive results,of which 11 cases received digital rectal examination.The average level of pre-biopsy tPSA was(23.28±44.94)μg/L with fPSA/tPSA ratio of 0.11±0.05 and PSAD of(0.55±1.07)μg/l/mL.The pre-biopsy mean MRI PI-RADS 2.0 was(4.6±0.6)in this group of patients.Extraprostatic invasion was shown on imaging in 4 patients.The average number of biopsy needles was(19.6±3.9),and the pathological results showed tuber-culous granulomas in 2 cases(15.4%)and non-specific granulomatous inflammation in 11 cases(84.6%).Five patients received local treatment of the prostate after pathological confirmation(PVP in 4 cases,TURP in 1 case),2 patients re-ceived anti-tuberculosis therapy,and 3 cases were given antibiotics.Average follow-up was(20.6±11.2)months,and the average tPSA were(6.94±4.96)μg/L at 3-6 months after biopsy and/or surgery,with no obvious signs of malignancy during the follow-up period.Conclusion GP is the great mimicker of prostate cancer clinically and radiologically.Pros-tate biopsy is the method for confirming the diagnosis.For patients who are considering biopsy-free radical prostatectomy,it is important to consider the possibility of GP.
9.Analysis of erectile dysfunction and its associated factors in male patients undergoing peritoneal dialysis
Xiaohui XU ; Man ZHANG ; Tingting ZHOU ; Juan NI
National Journal of Andrology 2025;31(10):915-920
Objective To investigate the prevalence proportion and influencing factors of erectile dysfunction in male patients receiving peritoneal dialysis(PD),and to provide a basis for clinical intervention.Methods A total of 170 male patients undergoing maintenance PD in Jinling Hospital from January to June 2025 were selected as the study subjects.And the international erectile function index-5 was used to evaluate sexual function of the patients.The general data,dialy-sis adequacy,nutritional status and other clinical indicators were collected.The logistic regression analysis was used to identify the influence factors of erectile dysfunction in the patients with PD.Results The incidence of erectile dysfunction in male patients with PD was 45.3%.And univariate analysis showed that age,education level,smoking history,dialysis-related symptoms and depressive status were significantly correlated with erectile dysfunction in male patients(all P<0.05).Ordered logistic regression analysis identified age,sleep duration,smoking history,albumin and total cholesterol as independent risk factors for erectile dysfunction in male patients with PD.Conclusion The incidence of erectile dys-function is relatively high in male patients with PD which is influenced by various physiological and psychological factors.Clinically,attention should be paid to patients' nutritional status,sleep quality,and other factors,with comprehensive in-terventions implemented to improve sexual function and overall quality of life.
10.Mechanisms of Wuzi Yuye Decoction in the treatment of diabetic oligoasthenozoospermia:Based on network pharmacology
Dandan HE ; Junjie WU ; Jinying SHEN ; Binbin ZHAO ; Jingyu ZHU ; Yi YU
National Journal of Andrology 2025;31(10):921-931
Objective The aim of this study is to systematically analyze the therapeutic mechanisms of Wuzi Yuye Decoction in diabetic oligoasthenozoospermia based on network pharmacology and animal experiments.Methods Active components and therapeutic targets of Wuzi Yuye Decoction were screened by integrating multiple databases,and their inter-section with diabetic oligoasthenozoospermia-related targets was obtained.Common targets were identified using the Venny platform,and protein-protein interaction(PPI)networks were constructed via the STRING database.And key targets were screened through topological analysis with Cytoscape.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed using the DAVID platform.A mouse model of diabetic oligoasthenozoospermia was established by high-fat diet combined with streptozotocin induction,followed by intervention with Wuzi Yuye Decoction.Body weight,testicular index,and sperm quality were assessed,while histopathological changes were evaluated by HE staining and transmission electron microscopy(TEM).In addition,ELISA,oxidative stress assays and Western blot were used to verify the changes in key pathway-related proteins.Results A total of 36 common targets were identified,including key nodes such as TNF,IL6 and IL1B.Enrichment analysis indicated that these targets were sig-nificantly involved in inflammatory responses,oxidative stress,autophagy-apoptosis regulation and reproduction-related pathways.Animal experiments confirmed that Wuzi Yuye Decoction markedly improved testicular mass and sperm motility in diabetic mice,reduced the levels of AGE,TNF-α,IL-6 and IL-1β in testicular tissues,alleviated oxidative stress damage,and restored autophagic flux and blood-testis barrier function by inhibiting the RAGE/NF-κB/mTOR signaling axis.Conclusion Wuzi Yuye Decoction improves the pathological progression of diabetic oligoasthenozoospermia by synergistically modulating multiple targets,including inflammation inhibition,antioxidant effects,autophagy regulation,and related pathways.

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