Evaluating the Role of Morphological Parameters in the Prostate Transition Zone in PHI-Based Predictive Models for Detecting Gray Zone Prostate Cancer.

Background: The early detection of clinically significant prostate cancer (csPCa) through the integration of multidimensional parameters presents a promising avenue for improving survival outcomes for this fatal disease. This study aimed to assess the contribution of prostate transition zone (TZ) to predictive models based on the prostate health index (PHI), with the goal of enhancing early detection of csPCa in the prostate-specific antigen (PSA) gray zone. Methods: In this observational cross-sectional study, a total of 177 PSA gray zone patients (total prostate-specific antigen [tPSA] level ranging from 4.0 to 10.0 ng/mL) were recruited and received PHI detections from August 2020 to March 2022. Prostatic morphologies especially the TZ morphological parameters were measured by transrectal ultrasound (TRUS). Results: Univariable logistic regression indicated prostatic morphological parameters including total prostate volume (PV) indexes and transitional zone volume indexes were all associated with csPCa (P < .05), while the multivariable analysis demonstrated that C-reactive protein (CRP), PHI, PHI density (PHID), and PHI transition zone density (PHI-TZD) were the 4 independent risk factors. The receiver-operating characteristic (ROC) curve analysis suggested that integrated predictive models (PHID, PHI-TZD) yield area under the curves (AUCs) of 0.9135 and 0.9105 in csPCa prediction, which shows a relatively satisfactory predictive capability compared with other predictors. Moreover, the PHI-TZD outperformed PHID by avoiding 30 patients' unnecessary biopsies while maintaining 74.36% specificity at a sensitivity of 90%. Decision-curve analysis (DCA) confirmed the comparable performance of the multivariable full-risk prediction models, without the inclusion of the net benefit, thereby highlighting the superior diagnostic efficacy of PHID and PHI-TZD in comparison with other diagnostic models, in both univariable and multivariable models. Conclusion: Our data confirmed the value of prostate TZ morphological parameters and suggested a significant advantage for the TZ-adjusted PHI predictive model (PHI-TZD) compared with PHI and PHID in the early detection of gray zone csPCa under specific conditions.

Cofilin-1 induces acute kidney injury via the promotion of endoplasmic reticulum stress-mediated ferroptosis.

Ischemia-reperfusion injury (IRI) leads to acute kidney injury (AKI), which poses serious threat to public health and society. Many clinical studies were conducted to evaluate several biomarkers in AKI, among which Cofilin-1 remains to be a very promising one. To explore the potential mechanism of Cofilin-1 in AKI, we established an oxygen-glucose-deprivation (OGD)-induced AKI cell model. The overexpression and knock-down Cofilin-1 were used for gain- and loss-of-function. Pharmacological inhibitors were employed to study the related pathways. The results showed that Cofilin-1 was significantly upregulated in AKI cells, knocking down Cofilin-1 protected cells against the effect of OGD treatment and alleviated AKI phenotypes. Overexpression of Cofilin-1 might induce AKI by triggering ferroptosis, inhibiting NF-κB signaling or ER stress pathway attenuated Cofilin-1 induced lipid peroxidation and AKI. We also validated our findings in IRI-induced AKI mouse models in vivo. Our work elucidated that Cofilin-1 might induce AKI via promoting ER stress-mediated ferroptosis and argues it as a biomarker for early diagnosis of AKI. We also expect to offer novel insights on future therapeutic interventions.

The association between body mass index and testosterone deficiency in aging Chinese men with benign prostatic hyperplasia: results from a cross-sectional study.

BACKGROUND AND OBJECTIVES: Evidence has supported obesity as a risk factor for both benign prostate hyperplasia (BPH) and hypogonadism. In this paper, we performed a retrospective study and discussed the prevalence of testosterone deficiency (TD) and its relationship to body mass index (BMI) in aging Chinese men with BPH who have surgical intervention. MATERIAL AND METHODS: We reviewed the clinical data by age, BMI, medical history, serum prostate-specific antigen (PSA) levels, serum total testosterone (TT) levels, biochemical analysis, and transrectal ultrasound. BMI and other variables were considered to be independent variables in an effort to evaluate any potential associations between these factors and TD status using non-adjusted and multivariate-adjusted regression models. RESULTS: Of the 795 BPH participants, 27.2% (216) patients had TD. After adjusting for all potential covariates, there was a similar J-shaped relationship between BMI and TD, with an inflection point of 19.2 kg/m2. The effect sizes and the confidence intervals on the left and right sides of this inflection point were 0.6 (0.4-1.0) (p = .043) and 1.2 (1.1-1.3) (p < .001), respectively. CONCLUSION: Nearly one-third of the aging Chinese BPH patients had TD in this study. The association between BMI and TD is not simple. A J-shaped curve correlation was detected. BMI was positively correlated with TD when it was over 19.2 kg/m2 and inversely correlated with TD when it was below 19.2 kg/m2. Long-term prospective studies are needed to confirm these findings.

Variation of prostatic morphology in Chinese benign prostatic hyperplasia patients of different age decades.

OBJECTIVE: Our study aimed to investigate the age-related growth in prostatic morphological parameters in Chinese benign prostatic hyperplasia (BPH) patients, and to find out the regularity of how these parameters change with aging. METHODS: Medical records of 1038 BPH patients were obtained from a retrospective database of first-visit men with BPH. Change regularity of prostatic anatomical factors with aging was analyzed. RESULTS: Patients were classified into four groups according to different age decades. All prostatic anatomical factors assessed in this research increased with age growth (p < .0001). However, these anatomical factors sustained stably when older than 70 years. By analyzing the detailed correlation between age and prostatic morphological parameters, transitional zone index (TZI) (Pearson r = 0.358, r2 = 0.128, p < .0001) and transitional zone width (TZW) (Pearson r = 0.344, r 2= 0.118, p < .0001) showed the best correlation coefficient with age. After adjusted the influence of cardiovascular disease (CVD) and diabetes mellitus (DM), the result remained still similarly. CONCLUSION: Prostatic morphological parameters increase progressively with age growth when patients were younger than 70 years, indicating reasonable interventions to be provided to BPH patients before 70 years. In addition, TZI and TZW are two practical, easy-to-measure prostatic parameters that are significantly associated with the growth of age compared to others.

The risk factors of Urethrocutaneous fistula after hypospadias surgery in the youth population.

BACKGROUND: The current research aims to evaluate the risk factors of urethrocutaneous fistula after hypospadias surgery among the youth in China. METHODS: One hundred twenty hypospadias patients were enrolled in our study. All of them were defined as Tanner 4 or 5. The information collected from the participants include age, urethral operation history, urinary comorbidities before operation, urine test before operation, body temperature before and after operation, type of surgical repair, chordee degree, urethral defect length and whether received vesicostomy after surgery or not. Independent t test, chi-square test and multivariate logistic regression were performed to evaluate the risk factor of urethrocutaneous fistula. RESULTS: Among the enrolled patients, 39 patients (32.5%) developed urethrocutaneous fistula after hypospadias repair. Our result showed significant association between the group with urethrocutaneous fistula and the group without urethrocutaneous fistula with respect to age, pyuria before operation, urethral defect length and the urethral operation history. The following logistic regression showed that urethral defect length and the urethral operation history were the risk factors of urethrocutaneous fistula. CONCLUSIONS: Urethral defect length and urethral operation history should be taken into consideration before undergoing hypospadias surgery since our study discovered that the risk of developing urethrocutaneous fistula after hypospadias repair is associated with urethral defect length and urethral operation history. Age, surgical procedure, type of surgical repair, chordee degree and other factors were not obviously related to the development of urethrocutaneous fistula.

Genetic variants in 5p13.2 and 7q21.1 are associated with treatment for benign prostatic hyperplasia with the α-adrenergic receptor antagonist.

BACKGROUND: The etiology of benign prostatic hyperplasia (BPH) has not been well established. The preferred medical treatment for many men with symptomatic benign prostatic hyperplasia is either an α-adrenergic receptor antagonist (α-blocker), or a 5α-reductase inhibitor. Single nucleotide polymorphism (SNP) is a powerful tool for successful implementation of individualized treatment. METHODS: Eighteen SNPs associated with drug efficacy in a Chinese population were genotyped in 790 BPH cases (330 aggressive and 460 non-aggressive BPH cases) and 1008 controls. All BPH patients were treated with α-adrenergic blockers for at least 9 months. We tested the associations between tagging single nucleotide polymorphism and BPH risk/aggressiveness, clinical characteristics at baseline, including the International Prostate Symptom Score (IPSS) and total prostate volume, and changes in clinical characteristics after treatment. RESULTS: There were nine SNPs associated with BPH risk, clinical progression and therapeutic effect. (1) There were nine tSNPs been chosen in CYP3A4, CYP3A5 and RANBP3L genes. (2) The SNP, rs16902947 in RANBP3L at 5p13.2 (p = .01), was significantly associated with BPH. (3) We found two SNPs, rs16902947 in RANBP3L at 5p13.2 (p = .0388) and rs4646437 in CYP3A4 at 7q21.1 (p = .0325), associated with drug effect. (4) Allele "G" for rs16902947 was found to be risk alleles for BPH risk (OR= 2.357, 95%CI 1.01-1.48). The "A" allele of rs4646437 was associated with lower IPSS at baseline (ß= -0.4232, p= .03255). CONCLUSIONS: rs16902947, rs16902947 and rs4646437 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.

Which Stage of ADPKD Is More Appropriate for Decortication? A Retrospective Study of 137 Patients from a Single Clinic.

OBJECTIVE: To study retrospectively the efficacy of decortication in patients with different stages of ADPKD and to determine which stage for decortication is more appropriate. MATERIALS AND METHODS: We analyzed 137 patients with ADPKD from 2001 to 2010. All patients were divided into three stages. A total of 70 patients underwent decortication, and we studied intraoperative indicators and postoperative indicators at 1 and 3 years follow-up. RESULTS: In 70 patients who underwent decortication, significant differences were observed in operative duration and bleeding volume between patients with stage I and II ADPKD (P<0.05), but no significant differences were observed in intestinal recovery time, pain medication dose, and the days of postoperative hospitalization (P > 0.05). The total complication occurrence rate was significantly different between them (P < 0.05). The serum creatinine (Scr) levels in patients with stage I ADPKD were within normal limits 1 and 3 years postoperatively and did not differ significantly (P > 0.05). Scr levels were significantly decreased in patients with stage II ADPKD in the 1st postoperative year (P < 0.05), but these were not significant differences in the 3rd postoperative year (P > 0.05). In the 1st postoperative year, VAS value, blood pressure and renal volume significantly differed (P < 0.05). However, no significant differences were observed 3 years later (P > 0.05). CONCLUSIONS: Decortication in patients with stage I ADPKD can alleviate back pain symptoms and decrease blood pressure within 1 year, but the long-term efficacy is not ideal. Scr levels can be maintained within normal limits, suggesting that decortication does not lead to deterioration of renal function. For patients with stage II ADPKD, decortication can significantly improve renal function over the short term. However, after 3 years, renal function returns to the preoperative level, and surgical difficulties and complications also increase.

A Misdiagnosed Vaginal Leiomyoma: Case Report.

Leiomyomas are common benign tumors in the uterus. They are rarely seen in the vaginal wall leading to pressure symptoms on urinary tract. Here we present a case of a 44-year-old Chinese woman, who had accepted hysterectomy, with a painless paraurethral mass associated with local discomfort. A complete surgical excision was performed by vaginal route, and the histology report confirmed the diagnosis of benign leiomyoma.

Androgen receptor promotes the oncogenic function of overexpressed Jagged1 in prostate cancer by enhancing cyclin B1 expression via Akt phosphorylation.

UNLABELLED: The Jagged1, a Notch signaling pathway ligand, had been shown to have a positive correlation with prostate cancer development. Our study for Jagged1 expression in 218 prostate cancer tissue samples also supports this conclusion. However, the detailed molecular mechanism of Jagged1 in promoting the progression of prostate cancer is still unclear. Through cell proliferation examination, androgen receptor (AR) was found to promote the oncogenic function of Jagged1 to enhance the cell proliferation rate by comparing four prostate cancer cell lines, LNCaP, LAPC4, DU145, and PC3, which was further validated through analyzing the survival of 118 patients treated with androgen-deprivation therapy (ADT) with different expression levels of Jagged1 and AR. More importantly, our data showed that Jagged1 combined with AR could increase the phosphorylation level of Akt and, in turn, phosphorylated Akt plays an important role in regulating the expression level of cyclin B1 by interacting with AR and increasing the transcriptional activity of AR. These data indicate that prostate cancer progression regulated by Jagged1 can be dramatically enhanced by combining with AR through promoting Akt activity. IMPLICATIONS: This study could benefit our clinical treatments for patients with prostate cancer with overexpressed Jagged1 by targeting AR and Akt.

[Staged hypospadias surgery for adult males].

OBJECTIVE: To explore the necessity of staged hypospadias surgery for adult men in order to improve the success rate of operation. METHODS: We retrospectively analyzed 52 cases of hypospadias treated in our department from January 2004 to January 2012. The patients were adult males at the mean age of 22 years and all had a history of urethroplasty, with curvature of the penis and scar tissues on the penile skin. We removed the scarred fibrous tissues on the ventral cavernosa and cut off the urethral plate following foreskin-degloving. For those still with penile curvature, we straightened the penis by plication of the dorsal tunica albuginea, with the length of the anterior urethral defect > 50% of that of the penis after penis-straightening. The patients were assigned to group 1 (n = 20) to receive stage-I foreskin vascular pedicle flap urethroplasty and group 2 (n = 32) to undergo foreskin-shaping at the ventral aspect of the penis following penile straightening to prepare the urethra plate for stage-II Duplay urethroplasty after 6-12 months. RESULTS: The success rates of urethroplasty were 25 and 56.3% in groups 1 and 2, respectively, with the post-urethroplasty incidence rates of urinary fistula of 50 and 21.9%, urethral stricture of 15 and 9.4%, local wound infection of 30 and 25%, and urethral rupture of 20 and 12.5%. There were statistically significant differences between the two groups in the incidence of urinary fistula and the success rate of urethroplasty, but not in urethral stricture, local wound infection and urethral rupture. CONCLUSION: For adult hypospadias patients with a history of urethroplasty, especially those with obvious penile curvature, long urethral defect and insufficient foreskin, staged hypospadias surgery is preferable, which can dramatically increase the success rate of second-stage urethroplasty.

[Transurethral plasmakinetic enucleation of the prostate for benign prostatic hyperplasia].

OBJECTIVE: To evaluate clinical application of transurethral plasmakinetic enucleation of the prostate (PKEP) to the treatment of benign prostatic hyperplasia (BPH). METHODS: A total of 90 BPH patients, aged 59-83 (mean 71) years and with indication of surgery, underwent transurethral resection of the prostate (the TURP group, n=50) and transurethral plasmakinetic enucleation of the prostate (the PKEP group, n=40), respectively. We recorded and analyzed the preoperative prostate volume, IPSS, QOL and Qmax, operation time, intra- and post-operative bleeding and complications, postoperative continuous bladder irrigation, and IPSS, QOL and Qmax at 2 weeks and 6 months after surgery. RESULTS: The preoperative prostate volume and operation time were 58.9 g and 58.8 min in the TURP group versus 58.3 g and 93.0 min in the PKEP group. Mild transurethral resection syndrome (TURS) appeared in 2 TURP receivers, while no abnormality was found in electrocardiogram monitoring in those undergoing PKEP. Continuous bladder irrigation was necessitated in 3 and urgent incontinence of urine occurred in 4 cases of TURP, as compared with 1 and 4 cases in the PKEP group. None of the 90 patients needed blood transfusion. At 2 weeks before and after surgery and 6 months postoperatively, IPSS averaged 19.7, 11.6 and 5.1, QOL 4.6, 3.3 and 1.1, and Qmax 6.3, 13.0 and 18.1 ml/s in the TURP group versus 18.6, 8.4 and 4.9 (IPSS), 4.5, 2.7 and 1.1 (QOL) and 6.9, 14.2 and 19.0 ml/s (Qmax) in the PKEP group. There were significant differences in operation time, IPSS and QOL at 2 weeks postoperatively between the two groups, as well as in IPSS, QOL and Qmax at 6 months before and after surgery (P < 0.01). But no remarkable differences were found in preoperative prostate volume, IPSS, QOL and Qmax, 6-month postoperative IPSS and QOL, and Qmax at 2 weeks and 6 months after surgery between the two groups (P > 0.01). CONCLUSION: Transurethral PKEP is a safe, effective and thorough surgical method to be chosen for the treatment of BPH.

[Experience in treating advanced prostate cancer with bladder outlet obstruction].

BACKGROUND & OBJECTIVE: The incidence and discovery rate of prostate cancer is increased in recent years; with advanced age and multiple organs dysfunction, the advanced prostate cancer patients have poor quality of life. This study was to explore suitable treatment for these patients. METHODS: A total of 80 advanced prostate cancer patients with bladder outlet obstruction were treated by transurethral electrovaporization of the prostate (TVP), plus castration and antiandrogen therapy. Preoperative individualized preparation was performed for each patient. International prostatic symptom score (IPSS), maximum flow rate of urine (Q(max)), prostatic-special antigen (PSA), and ultrasonography were measured before and 3 months after operation. RESULTS: TVP were successful in all cases. Postoperative IPSS was significantly lower than preoperative IPSS in patients with or without urine retention (13+/-3 vs. 31+/-2, 11+/-3 vs. 31+/-2, P<0.01); postoperative Q(max) was significantly higher than preoperative Q(max) in patients with or without urine retention [(19.0+/-3.3) ml/s vs. 0, (19.4+/-2.7) ml/s vs. (8.9+/-3.4) ml/s, P<0.01]. Postoperative PSA was significantly lower than preoperative PSA [(80.4+/-133.4) mg/L vs. (0.1+/-0.4) mg/L, P<0.05]. The volume of prostate was obviously reduced. CONCLUSION: TVP plus castration and endocrine therapy is a safe and effective treatment for advanced prostate cancer patients with bladder outlet obstruction.