HER2 expression in upper tract urothelial carcinoma and the relationship with clinicopathological characteristics-an analysis of 155 patients in Southwest China.

OBJECTIVE: We aimed to evaluate the expression of HER2 in patients with upper tract urothelial carcinoma (UTUC) in Southwest China by using a relatively large cohort, and to determine the relationship between HER2 expression and clinicopathological characters. MATERIALS AND METHODS: We retrospectively enrolled the clinical data of 155 UTUC patients who have undergone radical nephroureterectomy (RNU) from March 2019 to September 2022. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest (Scores of 0 or 1 + were considered as negative and 2 + or 3 + as positive). Tumor molecular phenotype was classified by the panel of CK20, CK5/6, and CD44. RESULTS: HER2 was overexpressed in 55 (35.5%) patients. It was associated with pathologic characteristics such as grade (p = 0.017), tumor molecular phenotype (p < 0.001) and Ki-67 expression (p = 0.017). On univariate and multivariable logistic regression analysis, HER2 overexpression remained associated with higher grade (HR, 10.6; 95% CI 1.0-112.6; p = 0.050) and luminal molecular phenotype (HR, 8.0; 95% CI 1,6-38.4; p = 0.010). During disease progression after nephroureterectomy, the phenotype of the tumor might change and a switch phenomenon in phenotype after recurrence in the bladder was reported. CONCLUSION: According to our study, in Southwest China, one-third of UTUC patients overexpressed HER2. Tumors with high grade or luminal phenotype tended to be HER2 positive. HER2 may represent a promising target for therapy in UTUC.

Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications.

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.

Current treatment for male infertility: an umbrella review of systematic reviews and meta-analyses.

This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration (n = 36), sperm morphology (n = 26), and sperm motility (n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% (n = 48), 25.6% (n = 23), and 21.1% (n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.

Transperineal 3-Core Magnetic Resonance Imaging Ultrasound Fusion Targeted Plus Laterally 6-Core Systematic Biopsy in Prostate Cancer Diagnosis.

INTRODUCTION: It is important to explore strategies reducing the number of SB cores taken to minimize biopsy-related morbidity and patient's discomfort during biopsy. This study aims to optimize prostate biopsy procedures by reducing the number of systematic biopsy (SB) cores while preserving cancer detection rates in the era of combined biopsy. PATIENTS AND METHODS: We prospectively recruited patients with ≥1 magnetic resonance imaging (MRI) lesions and they underwent transperineal combined 12-core SB+3-core targeted prostate biopsy (TB, reference standard). New strategy was defined as a laterally 6-core SB+3-core TB. Patients were served as their own control. Detection rates for overall prostate cancer (PCa) and clinically significant PCa (csPCa) were compared among the standard SB, MRI-TB, 6-core SB +3-core TB, and reference standard. Pathology consistency was assessed using the Kappa test. RESULTS: A total of 204 men were included, of which 111 (54.41%) and 92 (45.10%) harbored overall PCa and csPCa. Referenced combined biopsy detected significantly 6.86% (P = .0005) or 4.90% (P = .0044) more csPCa than performing only SB or 3-core TB, but was comparable to the new biopsy strategy. (45.10% vs. 43.14%, P = .1336) Similar results persisted when limiting patients in biopsy-naïve men or stratified by Prostate Imaging Reporting and Data System scores, PSAD, and index lesion parameters. Additionally, performing 6-core SB+3-core TB demonstrated high consistency with reference standard in grade group distribution (Kappa coefficient: 0.952 for all, 0.961 for biopsy-naïve men) and achieved superior sensitivity of 95.7% (All: 95% CI: 89.2%-99.8%) and 96.9% (Biopsy-naïve: 95% CI: 91.1%-99.7%), respectively. CONCLUSIONS: The 6-core SB+3-core TB approach maintains expected detection rates while reducing the total core count, offering a promising alternative to the reference standard, which may help to tailor transperineal combined biopsy procedures.

The Impact of Prostate Volume on Prostate Cancer Detection: Comparing Magnetic Resonance Imaging with Transrectal Ultrasound in Biopsy-naïve Men.

Background and objective: This study aimed to determine the difference in prostate volume (PV) derived from transrectal ultrasound (TRUS) and multiparametric magnetic resonance imaging (mpMRI), and to further investigate the role of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD in prostate cancer (PCa) detection in biopsy-naïve men. Methods: Patients who underwent an initial prostate biopsy within 3 mo after mpMRI between January 2016 and December 2021 were analyzed retrospectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of both TRUS-PSAD and mpMRI-PSAD for PCa detection were calculated and compared. The Pearson correlation coefficient, Bland-Altman plot, and receiver operating characteristic curve were also utilized to explore the interests of this study. Key findings and limitations: The median prostate-specific antigen level of 875 patients was 9.79 (interquartile range [IQR]: 7.09-13.50) ng/ml. The median mpMRI-PV and TRUS-PV were 41.92 (IQR: 29.29-60.73) and 41.04 (IQR: 29.24-57.27) ml, respectively, demonstrating a strong linear correlation (r = 0.831, 95% confidence interval: 0.809, 0.850; p < 0.01) and sufficient agreement. No significant difference was observed in terms of the sensitivity, specificity, PPV, and NPV between TRUS-PSAD and mpMRI-PSAD for any PCa and clinically significant PCa (csPCa) detection. The overall discriminative ability of TRUS-PSAD for detecting PCa or non-PCa, as well as csPCa and non-csPCa, was comparable with that of mpMRI-PSAD, and similar results were also observed in the subsequent analysis stratified by mpMRI-PV quartiles, prostate-specific antigen level, and age. The limitations include the retrospective and single-center nature and a lack of follow-up information. Conclusions and clinical implications: TRUS-PV and MRI-PV exhibited a strong linear correlation and reached sufficient agreement. The efficiency of TRUS-PSAD and mpMRI-PSAD for PCa detection was comparable. TRUS could be used for PV estimation and dynamic monitoring of PSAD, and TRUS-PSAD could effectively guide clinical decision-making and optimize diagnostic strategies. Patient summary: In this work, prostate volume (PV) derived from transrectal ultrasound (TRUS) exhibited a strong linear correlation with the PV derived from multiparametric magnetic resonance imaging (mpMRI). The efficiency of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD for the detection of prostate cancer was comparable. TRUS could be used for PV estimation and TRUS-PSAD could help in clinical decision-making and optimizing diagnostic strategies.

Preoperative Systemic Inflammation Score Predicts the Prognosis of Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy.

Background: To investigate the prognostic significance of systemic inflammation score (SIS) in upper tract urothelial carcinoma (UTUC) in patients undergoing radical nephroureterectomy (RNU). Methods: A total of 313 UTUC patients who underwent RNU at West China Hospital from May 2014 to June 2019 were retrospectively analyzed. The predictive value of SIS for relevant endpoints, including overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS), was assessed by Kaplan-Meier curves and the Cox proportional hazards model. Results: According to inclusion and exclusion criteria, 218 UTUC patients were ultimately included in this cohort study. Statistical analysis shows that increased SIS was significantly associated with higher TNM stage (p = 0.017), lower BMI (p = 0.037), absence of hemoglobin (p < 0.001), and pathologic necrosis (p = 0.007). Kaplan-Meier survival curves clearly visually stratified survival for the three outcomes. After adjusting for tumor grade, the multivariate Cox proportional hazards model results showed that SIS was an independent risk factor for poor OS and CSS (HR = 1.89, 95% CI: 1.11-3.21, p = 0.0183, HR = 1.89, 95% CI: 1.07-3.33, p = 0.0285) in the advanced group. Conclusions: SIS was an independent risk factor for OS and CSS after RNU in patients with high-grade UTUC. It may be a novel and conducive tool for preoperative risk stratification and guiding individualized therapy for high-risk UTUC patients.

Utilization trend of prebiopsy multiparametric magnetic resonance imaging and its impact on prostate cancer detection: Real-world insights from a high-volume center in southwest China.

BACKGROUND: Data on the utilization and effects of prebiopsy prostate multiparametric magnetic resonance imaging (mpMRI) to support its routine use in real-world setting are still scarce. OBJECTIVE: To evaluate the change of clinical practice of prebiopsy mpMRI over time, and assess its diagnostic accuracy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 6168 patients who underwent primary prostate biopsy (PBx) between January 2011 and December 2021 and had prostate-specific antigen (PSA) values ranging from 3 to 100 ng/mL. INTERVENTION: Prebiopsy MRI at the time of PBx. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed general linear regression and to elucidate trends in the annual use of prebiopsy mpMRI and conducted multivariable logistic regression to evaluate the potential benefits of incorporating prebiopsy mpMRI for prostate cancer (PCa) detection. RESULTS AND LIMITATIONS: The utilization of prebiopsy mpMRI significantly increased from 9.2% in 2011 to 75.0% in 2021 (p < 0.001). In addition, prebiopsy mpMRI significantly reduced negative PBx by 8.6% while improving the detection of clinically significant PCa (csPCa) by 7.0%. Regression analysis showed that the utilization of prebiopsy mpMRI was significantly associated with a 48% (95% confidence interval [CI]: 1.19-1.84) and 36% (95% CI: 1.12-1.66) increased PCa detection rate in the PSA 3-10 ng/mL and 10-20 ng/mL groups, respectively; and a 34% increased csPCa detection rate in the PSA 10-20 ng/mL group (95% CI: 1.09-1.64). The retrospective design and the single center cohort constituted the limitations of this study. CONCLUSIONS: Our study demonstrated a notable rise in the utilization of prebiopsy mpMRI in the past decade. The adoption of this imaging technique was significantly associated with an increased probability of detecting prostate cancer. PATIENT SUMMARY: From 2011 to 2021, we demonstrated a steady increase in the utilization of prebiopsy mpMRI among biopsy-naïve men. We also confirmed the positive impact of prebiopsy mpMRI utilization on the detection of prostate cancer.

The Prognostic Value of Preoperative Naples Prognostic Score in Upper Tract Urothelial Carcinoma Patients after Radical Nephroureterectomy.

This study aims to determine the prognostic value of preoperative Naples prognostic score (NPS) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). We conducted a retrospective study about UTUC patients at West China Hospital from January 2015 to June 2019. The X-Tile program was used to identify the optimal cutoff value of NPS. Overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were the endpoints of interest. Kaplan-Meier curves were used to estimate survival and Cox proportional hazard model was used for risk assessment. A total of 237 UTUC patients after RNU were identified and the threshold of NPS was determined to be 2. Preoperative high-NPS was associated with inferior OS (p = 0.004), CSS (p = 0.002) and PFS (p = 0.008), especially in locally advanced UTUC patients. Preoperative NPS was an independent predictor for OS (HR: 1.78; 95% CI: 1.08, 2.93), CSS (HR: 1.87; 95% CI: 1.11, 3.14) and PFS (HR: 1.60; 95% CI: 1.02, 2.50). The addition of NPS into the predictive model consisting of predictors from multivariate Cox regression resulted in better prediction performance. Preoperative NPS was a novel and reliable predictor for survival in UTUC patients after RNU, and should be further explored.

Survival impact of variant histology in patients with upper tract urothelial carcinoma after radical nephroureterectomy.

OBJECTIVE: To investigate the prognostic impact of variant histology (VH) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). MATERIALS AND METHODS: Data from 635 UTUC patients who underwent RNU at our institution from May 2003 to June 2019 were retrospectively acquired and analyzed. After propensity score matching (PSM), we investigated the impact of VH on overall survival (OS) and cancer-specific survival (CSS) by using cumulative incidence plots with the log-rank test, Cox regression models, and competing risk regression models. RESULTS: Overall, 121 (19.1%) patients were diagnosed with VH, including 68 (10.7%) with squamous cell differentiation (SCD) and 28 (4.4%) with adenocarcinoma differentiation (AD). After PSM, the presence of VH was significantly associated with worse OS (HR 1.70, 95% CI 1.25-2.32) and CSS (HR 1.64, 95% CI 1.17-2.31) only in locally advanced UTUC patients (pT>2). In the subgroup analysis, SCD revealed inferior outcomes (OS: HR 1.81, 95% CI 1.28-2.57; CSS: HR 1.73, 95% CI 1.18-2.54) compared with pure urothelial carcinoma (pUC), whereas AD conferred comparable outcomes. In addition, compared with pUC patients, SCD patients with extensive squamous components had significantly decreased OS (HR 4.17, 95% CI 1.84-9.44) and CSS (HR 1.10, 95% CI 0.61-1.99), whereas those with regional squamous components had similar survival outcomes. CONCLUSION: For UTUC patients after RNU, the presence of VH is associated with aggressive clinicopathological features and inferior survival outcomes. However, the survival outcomes of localized UTUC patients (pT≤2) with VH, and patients with the AD or regional SCD subtype are comparable to those of patients with pUC.

Development and validation of a multimorbidity risk prediction nomogram among Chinese middle-aged and older adults: a retrospective cohort study.

OBJECTIVES: The aim of this study is to establish a self-simple-to-use nomogram to predict the risk of multimorbidity among middle-aged and older adults. DESIGN: A retrospective cohort study. PARTICIPANTS: We used data from the Chinese Longitudinal Healthy Longevity Survey, including 7735 samples. MAIN OUTCOME MEASURES: Samples' demographic characteristics, modifiable lifestyles and depression were collected. Cox proportional hazard models and nomogram model were used to estimate the risk factors of multimorbidity. RESULTS: A total of 3576 (46.2%) participants have multimorbidity. The result showed that age, female (HR 0.80, 95% CI 0.72 to 0.89), chronic disease (HR 2.59, 95% CI 2.38 to 2.82), sleep time (HR 0.78, 95% CI 0.72 to 0.85), regular physical activity (HR 0.88, 95% CI 0.81 to 0.95), drinking (HR 1.27 95% CI 1.16 to 1.39), smoking (HR 1.40, 95% CI 1.26 to 1.53), body mass index (HR 1.04, 95% CI 1.03 to 1.05) and depression (HR 1.02, 95% CI 1.01 to 1.03) were associated with multimorbidity. The C-index of nomogram models for derivation and validation sets were 0.70 (95% CI 0.69 to 0.71, p=0.006) and 0.71 (95% CI 0.70 to 0.73, p=0.008), respectively. CONCLUSIONS: We have crafted a user-friendly nomogram model for predicting multimorbidity risk among middle-aged and older adults. This model integrates readily available and routinely assessed risk factors, enabling the early identification of high-risk individuals and offering tailored preventive and intervention strategies.

Transperineal magnetic resonance imaging targeted biopsy versus transrectal route in the detection of prostate cancer: a systematic review and meta-analysis.

PURPOSE: Magnetic resonance imaging (MRI) has deeply altered the prostate biopsy strategy to detect prostate cancer. However, it is still debatable whether the detection rate differs between transrectal (TR) and transperineal (TP) MRI-targeted biopsy (MRI-TB). To compare the effectiveness of these two methods for detecting both overall prostate cancer (PCa) and clinically significant PCa (csPCa), We performed a review and meta-analysis. METHODS: Until January 2023, we conducted a thorough search of Cochrane, Embase, Ovid, and PubMed. In total, 1482 references were identified, and 15 records were finally included. For PCa and csPCa discovered by TP and TR MRI-TB, we combined the relative sensitivity (RR) with 95% confidence intervals (CI). The RR between the TP and TR routes was established. RESULTS: Our study included 8826 patients in total and revealed that TP MRI-TB detected more PCa (RR 1.25 [95% CI 1.12, 1.39], p < 0.0001). In patients who underwent TP MRI-TB and TR MRI-TB at the same time or separately, TP MRI-TB had a greater detection rate of csPCa in per-patient analysis (one cohort (RR 1.33 [95% CI 1.09, 1.63], p = 0.005); two cohorts (RR 1.37 [95% CI 1.16, 1.61], p = 0.0002)). However, the detection rate of csPCa between the TP route and the TR route was comparable in per-lesion analysis (RR 0.91 [95% CI 0.76, 1.08], p = 0.28). Additionally, in the prostate's anterior region, we found that TP MRI-TB detected more csPCa (per-lesion (RR 1.52 [95% CI 1.04, 2.23], p = 0.03); per-patient (RR 2.55 [95% CI 1.56, 4.16], p = 0.0002)). CONCLUSION: According to this comprehensive study, TP MRI-TB is more effective than TR MRI-TB at detecting PCa and csPCa. Significant results persisted for detecting csPCa located in the anterior zone. The results need to be taken carefully notwithstanding the heterogeneity among the included studies.

An artificial intelligence method for predicting postoperative urinary incontinence based on multiple anatomic parameters of MRI.

Background: Deep learning methods are increasingly applied in the medical field; however, their lack of interpretability remains a challenge. Captum is a tool that can be used to interpret neural network models by computing feature importance weights. Although Captum is an interpretable model, it is rarely used to study medical problems, and there is a scarcity of data regarding MRI anatomical measurements for patients with prostate cancer after undergoing Robotic-Assisted Radical Prostatectomy (RARP). Consequently, predictive models for continence that use multiple types of anatomical MRI measurements are limited. Methods: We explored the energy efficiency of deep learning models for predicting continence by analyzing MRI measurements. We analyzed and compared various statistical models and provided reference examples for the clinical application of interpretable deep-learning models. Patients who underwent RARP at our institution between July 2019 and December 2020 were included in this study. A series of clinical MRI anatomical measurements from these patients was used to discover continence features, and their impact on continence was primarily evaluated using a series of statistical methods and computational models. Results: Age and six other anatomical measurements were identified as the top seven features of continence by the proposed model UINet7 with an accuracy of 0.97, and the first four of these features were also found by primary statistical analysis. Conclusions: This study fills the gaps in the in-depth investigation of continence features after RARP due to the limitations of clinical data and applicable models. We provide a pioneering example of the application of deep-learning models to clinical problems. The interpretability analysis of deep learning models has the potential for clinical applications.

The association between sex hormones and periodontitis among American adults: A cross-sectional study.

Introduction: After adulthood, as a person grows older, the secretion of sex hormones in the body gradually decreases, and the risk of periodontitis increases. But the relationship between sex hormones and periodontitis is still controversial. Methods: We investigated the association between sex hormones and periodontitis among Americans over 30 years old. 4,877 participants containing 3,222 males and 1,655 postmenopausal females who had had periodontal examination and detailed available sex hormone levels, were included in our analysis from the 2009-2014 National Health and Nutrition Examination Surveys cycles. We applied multivariate linear regression models to estimate the connection between sex hormones and periodontitis after converting sex hormones into categorical variables through tertile. Additionally, to ensure the stability of the analysis results, we carried out a trend test, subgroup analysis, and interaction test. Results: After fully adjusting the covariates, estradiol levels were not associated with periodontitis in both males and females with a P for trend = 0.064 and 0.064, respectively. For males, we found that sex hormone-binding globulin was positively associated with periodontitis (tertile3 vs tertile1: OR=1.63, 95% CI=1.17-2.28, p = 0.004, P for trend = 0.005). Congruously, free testosterone (tertile3 vs tertile1: OR=0.60, 95% CI=0.43-0.84, p = 0.003), bioavailable testosterone (tertile3 vs tertile1: OR=0.51, 95% CI=0.36-0.71, p < 0.001), and free androgen index (tertile3 vs tertile1: OR=0.53, 95% CI=0.37-0.75, p < 0.001) was found to be negatively associated with periodontitis. Moreover, subgroup analysis of age found a closer relationship between sex hormones and periodontitis in those younger than 50 years. Conclusion: Our research suggested that males with lower bioavailable testosterone levels affected by sex hormone-binding globulin were at a higher risk of periodontitis. Meanwhile, estradiol levels were not associated with periodontitis in postmenopausal women.

DOK3 promotes proliferation and inhibits apoptosis of prostate cancer via the NF-κB signaling pathway.

BACKGROUND: DOK3 (Downstream of kinase 3) is involved primarily with immune cell infiltration. Recent research reported the role of DOK3 in tumor progression, with opposite effects in lung cancer and gliomas; however, its role in prostate cancer (PCa) remains elusive. This study aimed to explore the role of DOK3 in PCa and to determine the mechanisms involved. METHODS: To investigate the functions and mechanisms of DOK3 in PCa, we performed bioinformatic and biofunctional analyses. Samples from patients with PCa were collected from West China Hospital, and 46 were selected for the final correlation analysis. A lentivirus-based short hairpin ribonucleic acid (shRNA) carrier was established for silencing DOK3. A series of experiments involving the cell counting kit-8, bromodeoxyuridine, and flow cytometry assays were performed to identify cell proliferation and apoptosis. Changes in biomarkers from the nuclear factor kappa B (NF-κB) signaling pathway were detected to verify the relationship between DOK3 and the NF-κB pathway. A subcutaneous xenograft mouse model was performed to examine phenotypes after knocking down DOK3 in vivo . Rescue experiments with DOK3 knockdown and NF-κB pathway activation were designed to verify regulating effects. RESULTS: DOK3 was up-regulated in PCa cell lines and tissues. In addition, a high level of DOK3 was predictive of higher pathological stages and worse prognoses. Similar results were observed with PCa patient samples. After silencing DOK3 in PCa cell lines 22RV1 and PC3, cell proliferation was significantly inhibited while apoptosis was promoted. Gene set enrichment analysis revealed that DOK3 function was enriched in the NF-κB pathway. Mechanism experiments determined that knockdown of DOK3 suppressed activation of the NF-κB pathway, increased the expressions of B-cell lymphoma-2 like 11 (BIM) and B-cell lymphoma-2 associated X (BAX), and decreased the expression of phosphorylated-P65 and X-linked inhibitor of apoptosis (XIAP). In the rescue experiments, pharmacological activation of NF-κB by tumor necrosis factor-α (TNF-α) partially recovered cell proliferation after the knockdown of DOK3. CONCLUSION: Our findings suggest that overexpression of DOK3 promotes PCa progression by activating the NF-κB signaling pathway.

Combining clinical parameters and multiparametric magnetic resonance imaging to stratify biopsy-naïve men for an optimum diagnostic strategy with prostate-specific antigen 4 ng ml-1 to 10 ng ml-1.

We attempted to perform risk categories based on the free/total prostate-specific antigen ratio (%fPSA), prostate-specific antigen (PSA) density (PSAD, in ng ml-2), and multiparametric magnetic resonance imaging (mpMRI) step by step, with the goal of determining the best clinical diagnostic strategy to avoid unnecessary tests and prostate biopsy (PBx) in biopsy-naïve men with PSA levels ranging from 4 ng ml-1 to 10 ng ml-1. We included 439 patients who had mpMRI and PBx between August 2018 and July 2021 (West China Hospital, Chengdu, China). To detect clinically significant prostate cancer (csPCa) on PBx, receiver-operating characteristic (ROC) curves and their respective area under the curve were calculated. Based on %fPSA, PSAD, and Prostate Imaging-Reporting and Data System (PI-RADS) scores, the negative predictive value (NPV) and positive predictive value (PPV) were calculated sequentially. The optimal %fPSA threshold was determined to be 0.16, and the optimal PSAD threshold was 0.12 for %fPSA ≥0.16 and 0.23 for %fPSA <0.16, respectively. When PSAD <0.12 was combined with patients with %fPSA ≥0.16, the NPV of csPCa increased from 0.832 (95% confidence interval [CI]: 0.766-0.887) to 0.931 (95% CI: 0.833-0.981); the detection rate of csPCa was similar when further stratified by PI-RADS scores (P = 0.552). Combining %fPSA <0.16 with PSAD ≥0.23 ng ml-2 predicted significantly more csPCa patients than those with PSAD <0.23 ng ml-2 (58.4% vs 26.7%, P < 0.001). Using PI-RADS scores 4 and 5, the PPV was 0.739 (95% CI: 0.634-0.827) when further stratified by mpMRI results. In biopsy-naïve patients with PSA level of 4-10 ng ml-1, stratification of %fPSA and PSAD combined with PI-RADS scores may be useful in the decision-making process prior to undergoing PBx.

Urinary polycyclic aromatic hydrocarbon metabolites are positively related to serum testosterone levels of males and serum estradiol levels of females among U.S. adults.

Background: It has been reported for several years that polycyclic aromatic hydrocarbons (PAHs) could disturb human endocrine function. However, there is still a short of consistent conclusion about the relationship between PAH exposure and levels of sexual hormones. The aim of our study is to explore whether exposure to PAHs and how PAHs affect the levels of serum testosterone (T) and estradiol (E2) in adults, hoping to fulfill the knowledge gap. Materials and methods: This study included adults aged 20 and above who participated in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. We included 10 PAH metabolites in this study. The levels of urinary PAH metabolites were log-transformed and divided into quartiles. The associations between PAH metabolites and both serum T levels of males and E2 levels of females were investigated using multivariate regression models. We furtherly calculated PAHs scores by sum of ranks across 10 PAHs metabolites, which represented the exposure levels of PAHs mixtures, and the association between PAHs scores and serum T and E2 levels were analyzed. Results: A total of 4,654 subjects were included in this study, including 2,460 males and 2,194 females. After adjusting for confounders, 2-hydroxynapthalene and 3-hydroxyfluorene were positively associated with serum T levels of males (p-value for trend=0.047, and p-value for trend=0.006, respectively), while 1-hydroxyphenanthrene was positively associated with serum E2 levels of females (p-value for trend=0.013). In the adjusted models, no significant association was found between PAHs scores and either T levels of males or E2 levels of females (p-value for trend=0.615, and p-value for trend=0.241, respectively). Conclusions: This study showed urinary 2-hydroxynapthalene and 3-hydroxyfluorene were associated with increased T levels of males, and urinary 1-hydroxyphenanthrene was associated with increased E2 levels of females. The observed association indicated disrupting effects of PAH exposure on reproductive health.

A single-sample mRNA molecular classification of bladder cancer predicting prognosis and response to immunotherapy.

Background: As an immunogenic cancer, crosstalk between cancer cells and immune cells has been gradually recognized in bladder cancer (BC). Several studies have emphasized the clinical significance of the molecular stratification of BC without highlighting the role of the immune microenvironment. Although immunotherapy acted as a prospective treatment, more precise molecular stratification should be established to select those sensitive to immunotherapy. Methods: To select specific immune genes forming subtypes indicating disparate prognoses, we performed bioinformatic analysis using BC transcriptomic profiles from six published datasets, with 408 BC samples in The Cancer Genome Atlas (TCGA) database and 295 individuals in International Cancer Genome Consortium (ICGC) database. Survival analyses were conducted using Kaplan-Meier curves, while Kruskal-Wallis tests were applied to test the differences among groups. Except for unsupervised clustering based on the differential expression of genes, we additionally performed binomial logistic regression, focusing on the mRNA level of a single sample. Results: Unsupervised clustering showed that 4 clusters captured the best segmentation. After validation with survival data and simplification using binomial logistic regression, we found that cluster B and cluster D showed worse survival outcomes (P=0.012). Considering the similar survival outcomes of these two clusters, we recombined and performed another survival analysis, which also showed significant survival differences (P=0.0041). Bonding with clinical data, a greater proportion of risk factors were assigned to the worse prognosis subtype, especially showing higher grades in the subtype (P<0.001). In addition, immune cell infiltration, single nucleotide polymorphism (SNP) and copy number variation (CNV) all showed differences between clusters, indicating changes in the immune microenvironment and mutation burden. Through phenotypical analysis, we found metabolism and proliferation phenotypes associated with the immune clusters and mutually exclusive in BC, of which proliferation contributed to worse outcomes. Using the tumor immune dysfunction and exclusion (TIDE) score, a worse immunotherapy benefit was predicted in clusters B&D, defined as the worse prognosis subtype. Conclusions: With this novel clustering criterion based on immune-related genes, we provide a better understanding of the immune microenvironment, further guiding the use of immunotherapy.

Blockade of integrin signaling reduces chemotherapy-induced premature senescence in collagen cultured bladder cancer cells.

Background: Diminished sensitivity towards chemotherapy remains the major impediment to the clinical treatment of bladder cancer. However, the critical elements in control of chemotherapy resistance remain obscure. Methods: We adopted improved collagen gels and performed cytotoxicity analysis of doxorubicin (DOX) and mitomycin C (MMC) of bladder cancer cells in a 3D culture system. We then detected the expression of multidrug resistant gene ABCB1, dormancy-associated functional protein chicken ovalbumin upstream-transcription factor 1 (COUPTF1), cell proliferation marker Ki-67, and cellular senescence marker senescence-associated ß-galactosidase (SA-ß-Gal) in these cells. We further tested the effects of integrin blockade or protein kinase B (AKT) inhibitor on the senescent state of bladder cancer. Also, we examined the tumor growth and survival time of bladder cancer mouse models given the combination treatment of chemotherapeutic agents and integrin α2ß1 ligand peptide TFA (TFA). Results: Collagen gels played a repressive role in bladder cancer cell apoptosis induced by DOX and MMC. In mechanism, collagen activated the integrin ß1/AKT cascade to drive bladder cancer cells into a premature senescence state via the p21/p53 pathway, thus attenuating chemotherapy-induced apoptosis. In addition, TFA had the ability to mediate the switch from senescence to apoptosis of bladder cancer cells in xenograft mice. Meanwhile, TFA combined with chemotherapeutic drugs produced a substantial suppression of tumor growth as well as an extension of survival time in vivo. Conclusions: Based on our finding that integrin ß1/AKT acted primarily to impart premature senescence to bladder cancer cells cultured in collagen gel, we suggest that integrin ß1 might be a feasible target for bladder cancer eradication.

The role of prostate-specific antigen density and negative multiparametric magnetic resonance imaging in excluding prostate cancer for biopsy-naïve men: clinical outcomes from a high-volume center in China.

This study aimed to assess the role of prostate-specific antigen density (PSAD) and negative multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer for biopsy-naïve men based on a large cohort of the Chinese population. From a prostate biopsy database between March 2017 and July 2021, we retrospectively identified 240 biopsy-naïve patients with negative prebiopsy mpMRI (Prostate Imaging Reporting and Data System version 2 [PI-RADS v2] score <3). Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer (csPCa). Receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) were performed to assess the diagnostic accuracy. The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8% (201/240) and 90.8% (218/240), respectively. ROC curve analysis indicated that PSAD was the most promising predictor, with an AUC value of 0.786 (95% confidence interval [CI]: 0.699-0.874), and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa (odds ratio [OR]: 10.99, 95% CI: 2.75-44.02, P < 0.001). Combining negative mpMRI and PSAD below 0.20 ng ml-2 obviously increased the predictive value in excluding PCa (91.0%, 101/111) or csPCa (100.0%, 111/111). If a PSAD below 0.20 ng ml-2 was set as the criterion to omit biopsy, nearly 46.3% of patients (463 per 1000) with negative mpMRI could safely avoid unnecessary biopsy, with approximately 4.2% of patients (42 per 1000) at risk of missed diagnosis of PCa and no patients with csPCa missed. A PI-RADS v2 score <3 and a PSAD <0.20 ng ml-2 could be potential criteria for the Chinese population to omit prompt biopsy safely.

Impact of occupational exposure on job satisfaction and overall happiness among Chinese physicians and nurses: A cross-sectional study.

AIMS: This study aims to investigate the impact of occupational exposure on job satisfaction and overall happiness and to identify related factors of job satisfaction and overall happiness among physicians and nurses. BACKGROUND: Occupational exposure against physicians and nurses has become one of the most serious public health issues worldwide. METHODS: A cross-sectional study was conducted among physicians and nurses from 14 public tertiary hospitals using purposive sampling. Propensity score matching was used to compare job satisfaction and overall happiness among physicians and nurses with and without occupational exposure. Furthermore, binary logistic regression analysis was used to identify and analyse the influencing factors of job satisfaction and overall happiness. RESULTS: A total of 2139 physicians and nurses (55.59%) from 3791 participants had experienced occupational exposure hazards. Before matching, the job satisfaction and overall happiness among the physicians and nurses were 38.54% and 42.14%, respectively. Participants who experienced occupational exposure were more likely to develop job dissatisfaction (OR = 1.08, 95% confidence interval [CI]: 0.90-1.28) and overall unhappiness (OR = 1.24, 95% CI: 1.05-1.46) than those who did not. Participants' work experience, self-evaluated health status, satisfaction with the work environment, evaluation of doctor-patient relationship and stress were common factors affecting job satisfaction and overall happiness. CONCLUSIONS: Our findings suggest that physicians and nurses who experience occupational exposure are more likely to develop job dissatisfaction and overall unhappiness, especially if they have shorter work experience and a tense or neutral relationship with patients. IMPLICATIONS FOR NURSING MANAGEMENT: It is necessary to pay attention to the occupational exposure. When physicians and nurses experience occupational exposure, managers could provide support to prevent job dissatisfaction and unhappiness.