Prostate Volume Growth Rate Changes over Time:Results from Men 18 to 92 Years Old in a Longitudinal Community-based Study

Previous investigations have shown that changes in total prostate volume（TPV） are highly variable among aging men,and a considerable proportion of aging men have a stable or decreasing prostate size.Although there is an abundance of literature describing prostatic enlargement in association with benign prostatic hyperplasia,less is known about the appropriate age cut-off points for TPV growth rate.In this community-based cohort study,TPV was examined once a year in men who had consecutive health checkup,during a follow-up of 4 years.A total of 5058 men（age 18–92 years old） were included.We applied multiple regression analyses to estimate the correlation between TPV growth rate and age.Overall,3232（63.9%） men had prostate growth,and 1826（36.1%） had a stable or decreased TPV during the study period.The TPV growth rate was correlated negatively with baseline TPV（r= –0.32,P〈0.001）.Among 2620 men with baseline TPV 〈15 cm^3,the TPV growth rate increased with age（β=0.98,95% CI：0.77%–1.18%） only up to 53 years old.Among 2188 men with baseline TPV of 15–33.6 cm3,the TPV growth rate increased with age（β=0.84,95% CI,0.66%–1.01%） only up to 61 years old after adjusting for factors of hypertension,obesity,baseline TPV,diabetes mellitus and dyslipidemia.In this longitudinal study,the TPV growth rate increased negatively with baseline TPV,only extending to a certain age and not beyond.Further research is needed to identify the mechanism underlying such differences in prostate growth.

A nomogram based on age, prostate-specific antigen level, prostate volume and digital rectal examination for predicting risk of prostate cancer

Nomograms for predicting the risk of prostate cancer developed using other populations may introduce sizable bias when applied to a Chinese cohort. In the present study, we sought to develop a nomogram for predicting the probability of a positive initial prostate biopsy in a Chinese population. A total of 535 Chinese men who underwent a prostatic biopsy for the detection of prostate cancer in the past decade with complete biopsy data were included. Stepwise logistic regression was used to determine the independent predictors of a positive initial biopsy. Age, prostate-specific antigen （PSA）, prostate volume （PV）, digital rectal examination （DRE） status, % free PSA and transrectal ultrasound （TRUS） findings were included in the analysis. A nomogram model was developed that was based on these independent predictors to calculate the probability of a positive initial prostate biopsy. A receiver-operating characteristic curve was used to assess the accuracy of using the nomogram and PSA levels alone for predicting positive prostate biopsy. The rate for positive initial prostate biopsy was 41.7% （223/535）. The independent variables used to predict a positive initial prostate biopsy were age, PSA, PV and DRE status. The areas under the receiver-operating characteristic curve for a positive initial prostate biopsy for PSA alone and the nomogram were 79.7% and 84.8%, respectively. Our results indicate that the risk of a positive initial prostate biopsy can be predicted to a satisfactory level in a Chinese population using our nomogram. The nomogram can be used to identify and counsel patients who should consider a prostate biopsy, ultimately enhancing accuracy in diagnosing prostate cancer.

Prostate volume as an independent predictor of prostate ：ancer in men with PSA of 10-50 ng ml-1

Prostate volume （PV） has been shown to be associated with prostate cancer （PCa） detection rates in men with a prostate-specific antigen （PSA） in the ＇grey zone＇ （2.0-10.0 ng ml-1）. However, the PSA ＇grey zone＇ in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10-50 ng ml-1, Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians （〈60 and ≥60 ml）, were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk （odds ratio, 0.02; P〈0.001） compared to other variables. The PCa rates in men with PVs measuring 〈60 and ≥ 60 ml in the 10-19.9 ng ml-1 PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20-50 ng ml- 1 were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10-50 ng ml-1. In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10-50 ng ml-1 regarding their PCa risks.

The influence of prostate volume on cancer detection in the Chinese population

In western populations, prostate volume （PV） has been proven to be one of the strongest predictors of detecting prostate cancer （PCa） in biopsies. We performed this study in a biopsy cohort, to evaluate associations among the prostate volume, prostate-specific antigen （PSA） and PCa detection in the Chinese population. Between the years, 2007-13, 1486 men underwent prostate biopsy at Huashan Hospital, Fudan University, Shanghai, China. The study population was divided into two groups for analysis according to total PSA （tPSA） range （4 ng m1-1 〈tPSA 〈20 ng m1-1 and tPSA 〉20 ng ml-1）. PV, age, tPSA, digital rectal examination （DRE） and transrectal ultrasound （TRUS） results were also included in the analysis. Although the positive biopsy rates decreased in both tPSA range groups, the downtrend was more pronounced in the 4 ng ml-2 〈tPSA 〈20 ng m1-1 group; therefore, we focused on 853 men in this group with increasing PV. In multivariate logistic regression analysis, only DRE was found to be associated with PCa in four PV groups （P 〈 0.05） and tPSA did not show a good predictive ability when PV exceeded 50 ml （P 〉 0.05）. Further, it may suggest that with increasing PV, the cancer detection rate decreased in men with different tPSA, DRE and TRUS nodule statuses （all P values for trends were 〈0.001）. Our study indicates that in tPSA ranging from 4 to 20 ng ml-1, the use of PV ranges of 0-35 ml, 35-50 ml and 〉50 ml might be taken into consideration for the biopsy decision-making in the Chinese population.

A novel equation and nomogram including body weight for estimating prostate volumes in men with biopsy-proven benign prostatic hyperplasia

Anthropometric measurements, e.g., body weight （BW）, body mass index （BMI）, as well as serum prostate-specific antigen （PSA） and percent-free PSA （%fPSA） have been shown to have positive correlations with total prostate volume （TPV）. We developed an equation and nomogram for estimating TPV, incorporating these predictors in men with benign prostatic hyperplasia （BPH）. A total of 1852 men, including 1113 at Tokyo Medical and Dental University （TMDU） Hospital as a training set and 739 at Cancer Institute Hospital （CIH） as a validation set, with PSA levels of up to 20 ng m1-1, who underwent extended prostate biopsy and were proved to have BPH, were enrolled in this study. We developed an equation for continuously coded TPV and a logistic regression-based nomogram for estimating a TPV grater than 40 mh Predictive accuracy and performance characteristics were assessed using an area under the receiver operating characteristics curve （AUC） and calibration plots. The final linear regression model indicated age, PSA, %fPSA and BW as independent predictors of continuously coded TPV. For predictions in the training set, the multiple correlation coefficient was increased from 0.38 for PSA alone to 0.60 in the final model. We developed a novel nomogram incorporating age, PSA, %fPSA and BW for estimating TPV greater than 40 mh External validation confirmed its predictive accuracy, with AUC value of 0.764. Calibration plots showed good agreement between predicted probability and observed proportion. In conclusion, TPV can be easily estimated using these four independent predictors.

Correlation of PSA Density to Prostate Cancer Based on Prostate Volume by 3.0 T MRI

Purpose: Prostate specific antigen levels can be normalized by the prostate volume to give a prostate specific antigen density (PSAd). Magnetic resonance imaging (MRI) can more accurately determine prostate zonal anatomy and prostate volumes compared to transrectal ultrasound, and hence may lead to more accurate PSAd measurements. Methods: Imaging and pathology of men undergoing prostate MRI from April 2007 to May 2009 were reviewed in this retrospective study. 73 patients were included for analysis, of which 45 had prostate cancer and 28 did not have cancer. Total, transitional zone, and peripheral zone values were determined by ultrasound prolate ellipse, MRI prolate ellipse, and MRI segmentation methods. Results: The study population showed an average PSA of 6.3 ng/mL, with the control mean PSA (8.8 ng/mL) being greater than the cancer group (5.3 ng/mL). Transrectal ultrasound underestimated the prostate volume (mean 27.7 mL versus MRI volume of 38.3 mL, p ≤ 0.001). No difference was seen between cancer and control populations using PSAd. PSAd correctly categorized low (Gleason < 7) and high-grade cancers (Gleason ≥ 7) in patients with malignancy. Conclusion: Transrectal ultrasound underestimates prostate volumes and hence is inaccurate in calculating PSAd. MRI more accurately depicts PSAd, however PSAd is unable to differentiate between patients with cancer and benign disease such as BPH or prostatitis.

The Effect of Prostate Volume on Robotic-assisted Radical Prostatectomy

Objective:To investigate the effect of prostate volume on robot-assisted radical prostatectomy.Methods:Clinical data of 75 patients underwent RARP in the Affiliated Hospital of Qingdao University were retrospectively analyzed.The patients were divided into 3 groups according to size of prostate.A total of 35 cases with prostate volume less than 30ml were recorded as group 1,27 cases with volume of 30 to 50 ml were recorded as group 2,and 13 cases with volume greater than 50ml were recorded as group 3.Age,BMI,preoperative PSA,operation time,intraoperative bleeding volume,postoperative drainage volume,indwelling time of catheter,indwelling time of drainage tube,total hospitalization time,pathological stage,surgical margin,urine control and biochemical recurrence were observed.Results:All operations were performed under Da Vinci robot assistance,and no patient was transferred to open surgery.There was no significant difference in age,preoperative PSA,BMI,operation time,intraoperative bleeding volume,postoperative drainage volume,indwelling time of catheter,total hospitalization time,pathological stage,rate of positive surgical margin and recovery of urinary continence between the groups.Indwelling time of drainage tube was longer in group with larger prostate,6.4(±4.5)days in group 1,6.3(±2.9)days in group 2 and 7.1(±2.5)days in group 3.Gleason score was lower in group with larger prostate,with statistical difference.Conclusion:Prostate volume had no significant effect on urinary control,rate of positive surgical margin and recurrence after RARP.Gleason score of pathological tissue was lower and indwelling time of drainage tube was longer in patients with larger prostate after RARP.Operation time and intraoperative bleeding volume of large prostate patients underwent RARP need to be further studied.RARP has certain advantages for patients with large prostate.

Free PSA performs better than total PSA in predicting prostate volume in Chinese men with PSA levels of 2.5–9.9 ng ml−1

This study investigated whether free prostate-specific antigen(fPSA)performs better than total PSA(tPSA)in predicting prostate volume(PV)in Chinese men with different PSA levels.A total of 5463 men with PSA levels of<10 ng ml^(−1) and without prostate cancer diagnosis were included in this study.Patients were classified into four groups:PSA<2.5 ng ml^(−1),2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1).Pearson/Spearman's correlation coefficient(r)and receiver operating characteristic(ROC)curves were used to evaluate the ability of tPSA and fPSA to predict PV.The correlation coefficient between tPSA and PV in the PSA<2.5 ng ml^(−1) cohort(r=0.422;P<0.001)was markedly higher than those of the cohorts with PSA levels of 2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1)(r=0.114,0.167,and 0.264,respectively;all P≤0.001),while fPSA levels did not differ significantly among different PSA groups.Area under ROC curve(AUC)analyses revealed that the performance of fPSA in predicting PV≥40 ml(AUC:0.694,0.714,and 0.727)was better than that of tPSA(AUC=0.545,0.561,and 0.611)in men with PSA levels of 2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1),respectively,but not at PSA levels of<2.5 ng ml^(−1)(AUC:0.713 vs 0.720).These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the"gray zone"(PSA levels of 2.5–9.9 ng ml^(−1)),but its performance was similar to that of tPSA at PSA levels of<2.5 ng ml^(−1).

Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts

BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.

Double-face urethroplasty in patients with obliterative bulbar strictures post-transurethral resection of the prostate mid-term outcomes in high-volume referral center

Objective Incidences of post-transurethral resection of the prostate(post-TURP)strictures are between 2.2%and 9.8%.Stricture commonly occurs within the first 6 months.Our objective was to assess the outcomes of patients with obliterative strictures post-TURP that underwent a double-face urethroplasty.Methods This is a single-center prospective study of 17 patients with obliterative proximal bulbar stricture post-TURP who underwent double-face graft urethroplasty by two surgeons between January 2014 and January 2020.We defined post-TURP obliterative strictures as those patients who presented with complete or almost complete obstruction of the urethral lumen and who have had a history of acute urine retention.We have excluded patients with bladder neck contracture.Primary outcome was treatment success,defined as the no need for further treatments.Secondary outcome was post-urethroplasty continent rate.Results Seventeen patients were included in the study with median age of 66(interquartile range 40-77)years;median time of follow-up was 24(interquartile range 12-84)months;median stricture length was 4(interquartile range 2-6)cm.Of the 17 patients,15(88.2%)were successful.All patients were continent after urethroplasty.Conclusion With mid-term follow-up,treatment of obliterative proximal bulbar strictures with double-face buccal mucosa graft is a safe and effective procedure.Obliterative proximal bulbar strictures merit double-face urethroplasty with high-rate success and functional outcomes.

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models.Mechanistically,ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets,JNK1/2 and C-Jun,in both PCa cells and mouse models,in an enzyme-independent manner.Importantly,the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models.Moreover,we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples,suggesting a potential regulatory role of ASPA in modulating LYN signaling.Conclusions:Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

Transurethral prostate surgery in prostate cancer patients: A population-based comparative analysis of complication and mortality rates

Objective:Prostate cancer(PCa)patients might experience lower urinary tract symptoms as those diagnosed with benign prostatic hyperplasia(BPH).Some of them might be treated for their lower urinary tract symptoms instead of PCa.We aimed to test the effect of PCa versus BPH on surgical outcomes after transurethral prostate surgery,namely complication and mortality rates.Methods:Within the American College of Surgeons National Surgical Quality Improvement Program database(2011-2016),we identified patients who underwent transurethral resection of the prostate,photoselective vaporization,or laser enucleation.Patients were stratified according to postoperative diagnosis(PCa vs.BPH).Univariable and multivariable logistic regression models evaluated the predictors of perioperative morbidity and mortality.A formal test of interaction between diagnosis and surgical technique used was performed.Results:Overall,34542 patients were included.Of all,2008(5.8%)had a diagnosis of PCa.The multivariable logistic regression model failed to show statistically significant higher rates of postoperative complications in PCa patients(odds ratio:0.9,95%confidence interval:0.7-1.1;p=0.252).Moreover,similar rates of perioperative mortality(p=0.255),major acute cardiovascular events(p=0.581),transfusions(p=0.933),and length of stay of more than or equal to 30 days(p=0.174)were found.Additionally,all tests failed to show an interaction between post-operative diagnosis and surgical technique used.Conclusion:Patients diagnosed with PCa do not experience higher perioperative morbidity or mortality after transurethral prostate surgery when compared to their BPH counterparts.Moreover,the diagnosis seems to not influence surgical technique outcomes.

Icariin plus curcumol enhances autophagy through the mTOR pathway and promotes cathepsin B-mediated pyroptosis of prostate cancer cells

Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.

What benefit can be obtained from magnetic resonance imaging diagnosis with artificial intelligence in prostate cancer compared with clinical assessments?

The present study aimed to explore the potential of artificial intelligence(AI)methodology based on magnetic resonance(MR)images to aid in the management of prostate cancer(PCa).To this end,we reviewed and summarized the studies comparing the diagnostic and predictive performance for PCa between AI and common clinical assessment methods based on MR images and/or clinical characteristics,thereby investigating whether AI methods are generally superior to common clinical assessment methods for the diagnosis and prediction fields of PCa.First,we found that,in the included studies of the present study,AI methods were generally equal to or better than the clinical assessment methods for the risk assessment of PCa,such as risk stratification of prostate lesions and the prediction of therapeutic outcomes or PCa progression.In particular,for the diagnosis of clinically significant PCa,the AI methods achieved a higher summary receiver operator characteristic curve(SROC-AUC)than that of the clinical assessment methods(0.87 vs.0.82).For the prediction of adverse pathology,the AI methods also achieved a higher SROC-AUC than that of the clinical assessment methods(0.86 vs.0.75).Second,as revealed by the radiomics quality score(RQS),the studies included in the present study presented a relatively high total average RQS of 15.2(11.0–20.0).Further,the scores of the individual RQS elements implied that the AI models in these studies were constructed with relatively perfect and standard radiomics processes,but the exact generalizability and clinical practicality of the AI models should be further validated using higher levels of evidence,such as prospective studies and open-testing datasets.

Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression

Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.

Effects of heat stress and long photoperiod on the prostate of rats

Objective:To examine light and heat effects on the morphological,histological,and micrometric structure of the prostate of rats.Methods:Thirty adult male rats were divided into three groups.The control group was kept under 20℃-22℃ and an artificial 12 h/12 h day/night cycle;the temperature group was under normal light and at(42±1)℃ heat for 4 to 5 h daily,and the light group was exposed to 8 h/16 h day/night cycle with 20℃-22℃.Rats were weighed five times(at the beginning of the study and every seven days).Five milliliters(mL)of their peripheral blood were taken.The tissue staining was performed using the hematoxylin-eosin(H&E)stain and periodic acid-Schiff(PAS).In the following,tissue and cellular reactions to the PAS were examined.Results:Folds were located entirely on the surface of the anterior lobe and periphery of the other lobes.The secretory units in the anterior lobe were more than the lateral lobe.A strong reaction of the secretory cells to the PAS was observed.Testosterone serum levels of the light group also significantly increased compared to the control group(P<0.05).The most histometric changes of the lobes were established in the lateral lobes.Heat stress resulted in a significant decrease in testosterone levels and transformed prostate tissue.The epithelium and parenchyma to scaffold ratio in the temperature group decreased.Conclusions:Maximum and minimum changes in the ventral lobe happened under the ascent of temperature and light,respectively.The ventral lobe in the study of prostatic hyperplasia should be more considered.

Attention Guided Multi Scale Feature Fusion Network for Automatic Prostate Segmentation

The precise and automatic segmentation of prostate magnetic resonance imaging(MRI)images is vital for assisting doctors in diagnosing prostate diseases.In recent years,many advanced methods have been applied to prostate segmentation,but due to the variability caused by prostate diseases,automatic segmentation of the prostate presents significant challenges.In this paper,we propose an attention-guided multi-scale feature fusion network(AGMSF-Net)to segment prostate MRI images.We propose an attention mechanism for extracting multi-scale features,and introduce a 3D transformer module to enhance global feature representation by adding it during the transition phase from encoder to decoder.In the decoder stage,a feature fusion module is proposed to obtain global context information.We evaluate our model on MRI images of the prostate acquired from a local hospital.The relative volume difference(RVD)and dice similarity coefficient(DSC)between the results of automatic prostate segmentation and ground truth were 1.21%and 93.68%,respectively.To quantitatively evaluate prostate volume on MRI,which is of significant clinical significance,we propose a unique AGMSF-Net.The essential performance evaluation and validation experiments have demonstrated the effectiveness of our method in automatic prostate segmentation.

Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

MAPK9 as a therapeutic target:unveiling ferroptosis in localized prostate cancer progression

Background:Ferroptosis,a lipid peroxidation-mediated programmed cell death,is closely linked to tumor development,including prostate cancer(PCa).Despite established connections between ferroptosis and PCa,a comprehensive investigation is essential for understanding its impact on patient prognosis.Methods:A risk model incorporating four ferroptosis-related genes was developed and validated.Elevated risk scores correlated with an increased likelihood of biochemical recurrence(BCR),diminished immune infiltration,and adverse clinicopathological characteristics.To corroborate these results,we performed validation analyses utilizing datasets from both the Cancer Genome Atlas Cohort(TCGA)and the Gene Expression Synthesis Cohort(GEO).Moreover,we conducted further investigations into the pivotal gene identified in our model to explore its impact on tumor characteristics through cell proliferation and invasion assays,as well as animal studies conducted in vivo.Additionally,we conducted further experiments involving ferroptosis-related analysis to validate its association with ferroptosis.Results:The risk model demonstrated exceptional predictive capabilities for prognosis and therapeutic outcomes in PCa patients.Mitogen-activated protein kinase 9(MAPK9)emerged as a crucial gene within the model.In vivo and in vitro experiments explored MAPK9’s role in ferroptosis and its influence on tumor migration and proliferation.Conclusion:The findings provide a novel perspective for advancing ferroptosis exploration in PCa,bridging basic research and clinical applications.