A novel clinically significant prostate cancer prediction system with multiparametric MRI and PSA: P.Z.A. score.

PURPOSE: This study aims to establish and validate a new diagnosis model called P.Z.A. score for clinically significant prostate cancer (csPCa). METHODS: The demographic and clinical characteristics of 956 patients were recorded. Age, prostate-specific antigen (PSA), free/total PSA (f/tPSA), PSA density (PSAD), peripheral zone volume ratio (PZ-ratio), and adjusted PSAD of PZ (aPSADPZ) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The nomogram was established, and discrimination abilities of the new nomogram were verified with a calibration curve and area under the ROC curve (AUC). The clinical benefits of P.Z.A. score were evaluated by decision curve analysis and clinical impact curves. External validation of the model using the validation set was also performed. RESULTS: The AUCs of aPSADPZ, age, PSA, f/tPSA, PSAD and PZ-ratio were 0.824, 0.672, 0.684, 0.715, 0.792 and 0.717, respectively. The optimal threshold of P.Z.A. score was 0.41. The nomogram displayed excellent net benefit and better overall calibration for predicting the occurrence of csPCa. In addition, the number of patients with csPCa predicted by P.Z.A. score was in good agreement with the actual number of patients with csPCa in the high-risk threshold. The validation set provided better validation of the model. CONCLUSION: P.Z.A. score (including PIRADS(P), aPSADPZ(Z) and age(A)) can increase the detection rate of csPCa, which may decrease the risk of misdiagnosis and reduce the number of unnecessary biopsies. P.Z.A. score contains data that is easy to obtain and is worthy of clinical replication.

Aberrant FBXW7-mediated ubiquitination and degradation of ZMYND8 enhances tumor progression and stemness in bladder cancer.

ZMYND8, an epigenetic regulator, was identified as a common oncogene across various tumors. However, little was reported about the association between ZMYND8 and bladder cancer. Besides, aberrant mechanisms that contribute to abnormal ZMYND8 expressions still remain unclear. In the current study, we first found that ZMYND8 protein levels were significantly elevated in Bca samples versus normal tissues, but not the mRNA levels. We then utilized the Cell Counting Kit-8 (CCK-8) assay, clone formation assay and transwell analysis to confirm that ZMYND8 could remarkably promote the tumor progression in vitro, including growth capacity and migration. Bioinformatic predictive analysis revealed that E3 ubiquitin ligase FBXW7 interacts directly with ZMYND8 and degrades ZMYND8 in a polyubiquitination manner. Low FBXW7 was a hazard factor for promoting and depending on accumulated ZMYND8 proteins to promote Bca progression. Gene set enrichment analysis (GSEA) further indicated that ZMYND8 was notably associated with stemness process, which was well functionally validated. Lastly, ZMYND8 deficiency was observed to inhibit tumor growth of Bca in vivo, revealing a promising translational significance in Bca treatment. In conclusion, our study for the first time provided evidence for a novel mechanism of FBXW7/ZMYND8 axis in Bca, providing therapeutic vulnerability for individualized cancer treatment.

Data-driven translational prostate cancer research: from biomarker discovery to clinical decision.

Prostate cancer (PCa) is a common malignant tumor with increasing incidence and high heterogeneity among males worldwide. In the era of big data and artificial intelligence, the paradigm of biomarker discovery is shifting from traditional experimental and small data-based identification toward big data-driven and systems-level screening. Complex interactions between genetic factors and environmental effects provide opportunities for systems modeling of PCa genesis and evolution. We hereby review the current research frontiers in informatics for PCa clinical translation. First, the heterogeneity and complexity in PCa development and clinical theranostics are introduced to raise the concern for PCa systems biology studies. Then biomarkers and risk factors ranging from molecular alternations to clinical phenotype and lifestyle changes are explicated for PCa personalized management. Methodologies and applications for multi-dimensional data integration and computational modeling are discussed. The future perspectives and challenges for PCa systems medicine and holistic healthcare are finally provided.

lncRNA MIR503HG functioned as a tumor suppressor and inhibited cell proliferation, metastasis and epithelial-mesenchymal transition in bladder cancer.

Bladder cancer is the most common malignancy with high recurrence. Currently, the long noncoding RNAs (lncRNAs) have been suggested to play vital roles in the pathogenesis of bladder cancer. The present study investigated the role of lncRNA MIR503 host gene (MIR503HG) in the pathogenesis of bladder cancer by using both in vitro and in vivo functional assays. The expression of MIR503HG was downregulated in bladder cancer tissues and cell lines. Low expression of MIR503HG was associated with advanced tumor stage, advanced histological grade, and lymph node metastasis. Ectopic expression of MIR503HG inhibited cell proliferation, cell growth, cell invasion, and migration, and also promoted cell apoptosis and inhibited cell cycle progression in SW780 cells. In parallel, T24 cells were used for loss-of-function studies. Knockdown of MIR503HG promoted the cancer cell proliferation and increased the migration and invasion abilities of T24 cells. In addition, knockdown of MIR503HG reduced the cell apoptotic rate in cancer cells and promoted cell cycle progression. Furthermore, MIR503HG overexpression decreased the epithelial-mesenchymal transition-related mRNA and protein levels of ZEB1, Snail, N-cadherin, and vimentin, with an increase in E-cadherin level. Consistently, knockdown of MIR503HG showed the opposite effects. In vivo xenograft, nude mice results showed that overexpression of MIR503HG suppressed the tumor growth and tumor metastasis. In conclusion, our results identified a novel lncRNA MIR503HG that exhibited significant antiproliferation, antimigration/invasion effects on bladder cancer cells both in vitro and in vivo, which may hold a therapeutic promise to treat bladder cancer.

Dual inhibition of BRD4 and PI3K by SF2523 suppresses human prostate cancer cell growth in vitro and in vivo.

Bromodomain-containing protein 4 (BRD4) and phosphatidylinositol 3-kinase (PI3K) are both key oncogenic proteins in human prostate cancer. In the current study, we examined the anti-prostate cancer cell activity by SF2523, a BRD4 and PI3K dual inhibitor. We showed that SF2523 potently inhibited survival and proliferation of the primary human prostate cancer cells. SF2523 induced profound apoptosis activation in prostate cancer cells. The dual inhibitor was yet non-cytotoxic to the prostate epithelial cells. At the molecular level, SF2523 downregulated BRD4-regulated genes (cyclin D1, c-Myc and androgen receptor) and almost blocked AKT-S6K1 activation in prostate cancer cells. In vivo, SF2523 intraperitoneal administration at the well-tolerated dose inhibited human prostate cancer xenograft growth in severe combined immunodeficient (SCID) mice. BRD4-regulated genes (cyclin D1, c-Myc and androgen receptor) and AKT-S6K1 activation were inhibited in SF2523-treated tumors. Together, dual inhibition of BRD4 and PI3K by SF2523 suppresses human prostate cancer cell growth in vitro and in vivo.

The Non-Peptide Vasopressin V1b Receptor Antagonist, SSR149415, Ameliorates Spermatogenesis Function in a Mouse Model of Chronic Social Defeat Stress.

To determine the effects of SSR149415 on testis and spermatogenesis in male mice subjected to chronic social defeat stress, C57BL/6 male mice were divided into two groups: Control and Stress. Then Stress group was subdivided into four subgroups administered water, SSR149415 (1 mg/kg/day), SSR149415 (10 mg/kg/day), SSR149415 (30 mg/kg/day), respectively. The behavioral alterations revealed by social interaction test and open field test were measured. The physical indices, including body weight and gonad weight (testis and epididymis) as well as testis/body weight and cauda epididymis/body weight were detected. Serum hormones, including testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined. Sperm count and abnormality as well as testicular histology structure were assessed. The germ cells apoptosis were also evaluated. Chronic social defeat stress-induced behavioral abnormality, as well as gonad atrophy (testis and epididymis) was significantly alleviated in stressed male mice exposed to SSR149415. Regressed serum testosterone levels and elevated serum FSH and LH levels exhibited by stressed male mice were observably reversed following SSR149415 administration. Chronic social defeat stress-induced damage in testicular histology structure and semen quality were also improved after SSR149415 administration. In addition, SSR149415 significantly reversed chronic social defeat stress-induced germ cells apoptosis. Overall, we provide clear evidence indicating the amelioration of chronic social defeat stress-induced behavioral abnormality and testicular dysfunction via SSR149415, promoting the development of drug-directed therapy against this disease. J. Cell. Biochem. 118: 3891-3898, 2017. © 2017 Wiley Periodicals, Inc.

Role of antibodies to human papillomavirus 16 in prostate cancer: A seroscreening by peptide microarray.

Evidence is accumulating in estimating the potential role of human papillomavirus infection in prostate carcinogenesis. However, the results remain inconclusive. We measured the serostatus of antibodies to one of the high-risk human papillomaviruses, human papillomavirus 16, with a newly developed peptide microarray. Serum samples were collected from 75 untreated prostate cancer patients, along with 80 control subjects. We identified 12 peptides with significant differences in prostate cancer samples from all 241 peptides derived from human papillomavirus 16. Our results showed human papillomavirus 16 infection in 64.0% of prostate cancer serum samples, which is significantly different compared with the controls ( p < 0.01) because only 17.5% of the control serum was considered seropositive. The area under the receiver operator characteristic curve was 0.793 (95% confidence interval 0.721-0.864), indicating that the new microarray technique may have diagnostic value. The results showed an association between serological evidence for human papillomavirus 16 infection and risk of prostate cancer. The different serostatus of antibodies in the two subgroups indicated that human papillomavirus 16 infection might occur and play a potential role of progression in a minority of prostate cancer.

The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion.

Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of renal cell carcinoma (RCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 307 cases of RCC tissues and 34 normal renal tissues. The Cul1 expression was increased significantly in RCC and was correlated with renal carcinoma histology grade (P = 0.007), tumor size (P = 0.013), and pT status (P = 0.023). Also, we found that silencing of Cul1 leads to increased expression of p21 and p27 that could inhibit the cyclin D1 and cyclin E2 expressions and arrest cell cycle at the G1 phase. Furthermore, knockdown of Cul1 inhibits RCC cell migration and invasion abilities by up-regulating the expression of TIMP-1 which could inhibit the expression of MMP-9. Finally, using bioluminescence imaging, we found that Cul1 knockdown significantly reduced the tumor growth in vivo. Cul1 may constitute a potential therapeutic target in RCC.

Comparison of Treatment Outcomes of Different Spermatic Vein Ligation Procedures in Varicocele Treatment.

In this study, 4 different spermatic vein ligation procedures for varicocele (VC) treatment were compared based on recurrence rate, postoperative complications, and semen quality. Between January 2012 and May 2013, a total of 345 male patients with VC were recruited at The First Affiliated Hospital of Soochow University. Patients were performed by different ligation procedures, and they were divided into 4 groups: laparoscopic varicocelectomy group (LV group: n = 84), microscopic inguinal varicocelectomy group (MIV group: n = 85), microscopic retroperitoneal varicocelectomy group (MRV group: n = 86), and microscopic subinguinal varicocelectomy group (MSV group: n = 90). In MSV group, the operative time was 55 ± 6.9 minutes, which was significantly longer than LV, MIV, and MRV groups (P < 0.05). Recurrence rate in LV group was at 11.9%, the highest rate observed compared with the MIV, MRV, and MSV groups (P < 0.05). Scrotal edema and testicular atrophy in MSV group were markedly decreased (P < 0.05), and scrotal pain was relieved in almost all patients in the MSV group at a significantly higher rate than LV, MIV, and MRV groups (P < 0.05). Sperm concentration, sperm count of grades a + b, and sperm motility (%) in the MSV group were sharply higher than LV, MIV, and MRV groups (all P < 0.05). Our study indicates that MSV is the most beneficial of the 4 spermatic vein ligation procedures and may be offered as the first-line treatment for VC in infertile men.

Application of transrectal ultrasound-guided repeat needle biopsy in the diagnosis of prostate cancer in Chinese population: A retrospective study.

BACKGROUND: Transrectal ultrasound-guided repeat needle biopsy (TUGRNB) is widely used for diagnosis of prostate cancer (PCa). However, significance of TUGRNB in Chinese population was rarely reported. A retrospective study was conducted to evaluate the significance of TUGRNB applied in prediction of PCa in Chinese population. MATERIALS AND METHODS: A total of 960 from January 2009 to December 2012 were included. Repeat needle biopsy rate and PCa positive detection rate were evaluated. Relationship between prostate specific antigen (PSA) levels and PCa positive rates was analyzed. RESULTS: PCa positive detection rate after initial needle biopsy was 28.4%, which was lower than the rate of repeat needle biopsy (40%). The rate for immediate transurethral resection (TUR), surgery after initial needle biopsy, was 27.1%, however with a low PCa positive detection rate (0.66%). The repeat needle biopsy rate was lower compared with the initial biopsy rate (P < 0.05). Meanwhile, immediate TUR rate was significantly higher than that of the repeat needle biopsy rate (P < 0.05). Among the three groups, the PCa positive detection rate in repeat needle biopsy group was the highest. In subgroups with different PSA levels, the PCa positive rate increased with the elevation of PSA level. In cases with PSA > 20 ng/ml, PCa positive rate was significantly higher than those with PSA < 20 ng/ml (P < 0.05). CONCLUSION: PCa positive detection rate following repeat needle biopsy in Chinese population was higher, although the repeated needle biopsy rate was still in a low level. TUGRNB should attract more attention in the diagnosis of PCa.

Effects of Icariside II on corpus cavernosum and major pelvic ganglion neuropathy in streptozotocin-induced diabetic rats.

Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II) on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily). Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining) and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro) was greatly attenuated in the ICA II-treated group (p < 0.01). ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes.

[Continuous observation of changes in renal function after radical nephrectomy].

OBJECTIVE: To evaluate continuous change in renal function by various clinical factors after radical nephrectomy (RN). METHODS: Patients after RN from January 2007 to December 2011 in the First Affiliated Hospital to Soochow University were enrolled, 356 cases continuously enrolled throughout the follow-up process, because of lost, missing data and other material reasons, 185 cases meet the requirements, eventually, including 121 male and 64 female patients, aged from 30 to 88 years (average age: (58 ± 12) years). There were 34 diabetes mellitus, 82 hypertension patients. Open surgery for 132 cases, laparoscopic surgery for 53 cases. Continuous checked serum creatinine at 3, 6, 9, 12, 24, 36, 48, 60, 72 months after RN and calculated to estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease equation.Linear mixed models were carried out to analyze postoperative continuous change in eGFR in multivariate regression analysis postoperative risk factors for changes in renal function. RESULTS: Overall, there was a subsequent restoration of renal function over the follow-up period. The slope (ß) for the relationship between the eGFR and the time since RN was 0.099 (95%CI:0.07-0.13, P < 0.01) indicating that each month after RN was associated with an increase in eGFR of 0.099 ml×min(-1)×(1.73 m(2))(-1)×month(-1). The slope (ß) was different between the group with clinical factor and its reference group, but the difference in the next three groups with statistically significant after multivariate regression analysis:diabetic and non-diabetic mellitus patients with a slope (ß) of -0.02 and 0.12 (P < 0.01) .Hypertension and non-hypertensive patients with a slope (ß) of 0.08 and 0.11 (P < 0.05). Age ≤ 50 years, > 50-65 years and > 65 years patients with a slope (ß) of 0.15,0.09 and 0.05 (P < 0.05), respectively. There were 13 new-onset of chronic kidney disease (CKD) after RN, including 9 patients with CKD III and 4 patients with CKD IV. CONCLUSIONS: Renal function recover continuously during the follow-up period after RN. Preoperative predictors of an increase in eGFR after RN are young age, no diabetes mellitus, no hypertension.

Cost-effectiveness analysis of different anesthesia strategies for transperineal MRI/US fusion prostate biopsy.

This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (<40 ml), TIVA emerged as a more cost-effective strategy. While Chat-LA may generally be the most cost-effective and safer anesthesia method for TP-MUF-PB, personalization of anesthesia strategies is crucial, considering specific patient demographics such as age and prostate volume.

Randomized prospective trial of tubeless versus conventional minimally invasive percutaneous nephrolithotomy.

PURPOSE: To evaluate the effectiveness and safety of minimally invasive percutaneous nephrolithotomy (mPCNL) without nephrostomy drainage tubes. METHODS: We prospectively enrolled 32 eligible patients with kidney stones at our hospital. Patients were randomly assigned to a conventional mPCNL group (ureteric Double-J stents and nephrostomy drainage tubes) or a tubeless mPCNL group (ureteric catheter but no drainage tubes). A single experienced surgeon performed all operations. RESULTS: At baseline, the two groups had similar age, maximum stone diameter, and gender distribution. There were no significant differences in operation time, presence of postoperative fever, stone clearance, and level of postoperative serum hemoglobin. However, the tubeless mPCNL group had significantly shorter hospital stays (3 vs. 4 days, p = 0.032) and significantly less back pain (5 patients vs. 14 patients, p = 0.003) than the conventional mPCNL group. CONCLUSIONS: No significant differences were found between conventional and tubeless mPCNL in safety issues and stone clearance rate. However, patients treated with tubeless mPCNL had shorter hospitalization stays and were less likely to experience back pain.

Urethral reconstruction using allogenic frozen-thawed bladder mucosa: an experimental study.

OBJECTIVE: To determine the feasibility and effectivity of allogenic frozen-thawed bladder mucosa for urethroplasty. METHODS: Bladder mucosa was harvested from 6 New Zealand rabbits. Changes in the bladder mucosa as seen by histological and electron microscope examination were compared between the frozen-thawed and fresh groups. Twelve urethral stricture models were established and randomly divided into two groups. In the test group, we performed urethroplasty with allogenic frozen-thawed bladder mucosa, and the same operation was done in the control group, but using fresh bladder mucosa. The result of retrograde urethrography and histological changes of the urethral sample were compared postoperatively. RESULTS: No obvious changes on histological and electron microscope examination were observed in the frozen-thawed bladder mucosa. Inflammation reaction of the surgical site in the test group was milder than that of the controls 2 weeks after surgery. The urethral epithelial cells grew well 2 weeks after surgery, but lots of epithelia were necrotic in the control group. The urethra of all rabbits in the test group had good continuity and the urethral lumen was large in the test group 2 months after surgery. There was a layer of urethral epithelium in the test group 2 months after surgery, whereas scar tissue was found in the control group. CONCLUSIONS: The freeze-thaw technique can maintain bladder mucosa structure and biological function. Frozen-thawed allogenic bladder mucosa may be a potential material for urethroplasty.

New model of PIRADS and adjusted prostatespecific antigen density of peripheral zone improves the detection rate of initial prostate biopsy: a diagnostic study.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

The effect of programmed cryopreservation on immunogenicity of bladder mucosa in New Zealand rabbits.

A significant reduction in immunogenicity has been observed in some frozen-thawed tissues after cryopreservation. The objective of this study was to evaluate the effects of programmed cryopreservation on immunogenicity of rabbit bladder mucosa and on the extent of immunological rejection caused by the allograft. This study would provide theoretical support for the application of allogenic frozen-thawed bladder mucosa in the treatment of urethral stricture. Forty-two adult male New Zealand rabbits were used in this study. The immunogenicity was detected by mixed lymphocyte reaction using the allograft of bladder mucosa (fresh and frozen-thawed) and spleen lymphocytes. Twelve urethral stricture models were established in New Zealand rabbits for substitution urethroplasty using the allograft of bladder mucosa, which were divided into fresh and frozen-thawed group. Two weeks after operation, lymphocyte proliferation was detected in both blood and spleen of recipient rabbits. At the same time, immunohistochemical staining of urethral allograft was performed and the expression of CD3, CD4 and CD8 were observed. The mRNA of bladder mucosa (fresh and frozen-thawed) was extracted and the expressions of RLA-I, RLA-II and RLA-III gene were detected by real-time PCR. By mixed lymphocyte reaction, we found that allogenic lymphocyte proliferation stimulated by frozen-thawed bladder epithelial cells was significantly weaker than that of the fresh cells. The blood and spleen lymphocytes from fresh bladder mucosa group showed significantly higher proliferation rate than frozen-thawed group. Compared with the fresh group, the expression of CD3+ and CD8+ T cells infiltrated in the operation locus of bladder mucosa urethroplasty was significantly decreased in the frozen-thawed group. However, the expressions of RLA genes did not change significantly after the freeze-thaw procedure. This study demonstrates for the first time that a programmed freeze-thaw procedure of rabbit bladder mucosa could reduce its immunogenicity in allogenic bladder mucosa urethroplasty and thus restrict the extent of immunological rejection, therefore, provides theoretical support for the application of frozen-thawed bladder mucosa in the treatment of urethral stricture.

Development and validation of a nomogram for predicting the overall survival of prostate cancer patients: a large population-based cohort study.

Background: Prostate cancer (PC) is the second most common malignant tumor, and its survival is of great concern. However, the assessment of survival risk in current studies is limited. This study is to develop and validate a nomogram for the prediction of survival in PC patients using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: A total of 153,796 PC patients were included in this cohort study. Patients were divided into a training set (n=107,657) and a testing set (n=46,139). The 3-, 5- and 10-year survival of the PC patients were regarded as the outcomes. Predictors based on the demographic and pathological data for survival were identified by multivariate Cox regression analysis to develop the predictive nomogram. Internal and subgroup validations were performed to assess the predictive performance of the nomogram. The C-index, time-dependent receiver operating characteristic (ROC) curves, and corresponding areas under the ROC curves (AUCs) were used to estimate the predictive performance of the nomogram. Results: Age at diagnosis, race, marital status, tumor node metastasis (TNM) stage, prostate specific antigen (PSA) status, Gleason score, and pathological stage were identified as significantly associated with the survival of PC patients (P<0.05). The C-index of the nomogram indicated a moderate predictive ability [training set: C-index =0.782, 95% confidence interval (CI): 0.779-0.785; testing set: C-index =0.782, 95% CI: 0.777-0.787]. The AUCs of this nomogram for the 3-, 5-, and 10-year survival were 0.757 (95% CI: 0.756-0.758), 0.741 (95% CI: 0.740-0.742), and 0.716 (95% CI: 0.715-0.717), respectively. The results of subgroup validation showed that all the AUCs for the nomogram at 3, 5, and 10 years were more than 0.70, regardless of marital status and race. Conclusions: We developed a nomogram with the moderate predictive ability for the long-term survival (3-, 5-, and 10-year survival) of patients with PC.

Prognostic significance of sarcopenia and systemic inflammation for patients with renal cell carcinoma following nephrectomy.

Background: To clarify the prognostic effect of preoperative sarcopenia and systemic inflammation, and to develop a nomogram for predicting overall survival (OS) of patients with renal cell carcinoma (RCC) following partial or radical nephrectomy. Methods: Patients with RCC following nephrectomy from the First Affiliated Hospital of Soochow University during January 2018 to September 2020 were included in this study. The relationship between sarcopenia and inflammatory markers was identified by logistic regression analysis. Then univariable Cox regression analysis, LASSO regression analysis and multivariable Cox regression analysis were analyzed sequentially to select the independent prognostic factors. Kaplan-Meier survival curves were applied to ascertain the prognostic value. Finally, the identified independent predictors were incorporated in a nomogram, which was internally validated and compared with other methods. Results: A total of 276 patients were enrolled, and 96 (34.8%) were diagnosed with sarcopenia, which was significantly associated with neutrophil-to-lymphocyte ratio (NLR). Sarcopenia and elevated inflammation markers, i.e., NLR, platelet-to-lymphocyte ratio (PLR) and the modified Glasgow Prognostic Score (mGPS), were independent factors for determining the OS. The model had good discrimination with Concordance index of 0.907 (95% CI: 0.882-0.931), and the calibration plots performed well. Both net reclassification index (NRI) and integrated discriminant improvement (IDI) exhibited better performance of the nomogram compared with clinical stage-based, sarcopenia-based and integrated "NLR+PLR+mGPS" methods. Moreover, decision curve analysis showed a net benefit of the nomogram at a threshold probability greater than 20%. Conclusions: Preoperative sarcopenia was significantly associated with NLR. A novel nomogram with well validation was developed for risk stratification, prognosis tracking and personalized therapeutics of RCC patients.

Comparison of MRI/US Fusion Targeted Biopsy and Systematic Biopsy in Biopsy-Naïve Prostate Patients with Elevated Prostate-Specific Antigen: A Diagnostic Study.

Purpose: This study aimed to compare the detection rate of prostate cancer (PCa) between targeted biopsy and systematic biopsy. Patients and Methods: A total of 671 patients who underwent both targeted biopsy and systematic biopsy were included in this study. The stratified analysis was conducted based on Prostate Imaging Reporting and Data System (PIRADS) scores, region of interest load (ROI-load). Results: There was no statistical difference in the detection rate of PCa patients between systematic biopsy and targeted biopsy (44.41% vs 45.6%, P>0.05), while the detection rate of targeted biopsy in clinically significant PCa (csPCa) patients was slightly higher than that of systematic biopsy (40.83% vs 38.15%, P=0.033). Stratified analysis indicated that targeted biopsy was more advantageous in csPCa patients with PIRADS score ≥ 4 and ROI-load > 5%. The comparison of diagnostic sensitivity of systematic biopsy and targeted biopsy demonstrated that targeted biopsy was more sensitive than systematic biopsy to diagnose PCa (Z=2.110, P=0.035) at ROI-load ≤ 5%. In addition, ROI-load may be a better targeted biopsy indicator than ROI diameter for the diagnosis of PCa (Z=2.168, P=0.030). Conclusion: MRI/US fusion targeted biopsy may be more suitable for PCa detection than systematic biopsy in patients with low ROI-load.