Abstract Background Conflicting results on testicular stiffness in varicocele and the lack of a standardized measurement protocol hinder clinical staging. In this study, we aimed to investigate the effects of probe frequency and region of interest (ROI) size selection on testicular stiffness measurements and to evaluate the testicular parenchymal stiffness and volume changes in patients with varicocele compare with healthy controls under standardized conditions. Results Shear wave elastography (SWE) was first performed on 62 testes from 31 healthy men, with two probe frequencies (SL10–2 and SL15–4) and four ROI sizes (4, 6, 8, and 10 mm), to assess the impact on SWE measurements. Based on the lowest variability settings, testicular volume and stiffness were compared in 76 patients with varicoceles and 68 healthy controls. Different SWE values were obtained with the two probes and four ROI sizes (p < 0.05). The SL15–4 probe showed lower variability, with the lowest coefficient of variation at the 4 mm ROI. The median testicular SWE value was 2.03 (1.97–2.07) kPa in the control group and 2.01 (1.87–2.07), 1.77 (1.53–1.98), and 1.51 (1.45–1.63) kPa in the Grade I, II, and III varicocele groups, respectively. SWE values were significantly lower in varicocele patients and decreased with increasing grade. The median testicular volumes were 13.08 (12.06–15.70) mL in the control group and 12.26 (10.70–15.15), 13.06 (11.34–14.72), and 11.84 (11.26–12.86) mL in the Grade I, II, and III varicocele groups, respectively. No significant difference in volume was observed between varicocele and control groups (p = 0.387). Conclusion Probe frequency and ROI size influence testicular SWE measurements, and caution should be exercised when comparing SWE results. Our study showed that testicular stiffness was decreased in patients with varicocele without significant changes in testicular volume, suggesting the presence of subtle structural alterations. SWE may provide complementary information by detecting changes in testicular parenchymal in patients with varicocele.

Background:The association between prostate volume (PV) and lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH) is inconsistent, as significant symptoms frequently occur even with small prostates. Although ultrasonography noninvasively ascertains anatomical parameters, such as intravesical prostatic protrusion (IPP) and bladder neck angle (BNA), their predictive value across different prostate sizes remains unclear. We aimed to examine the association between prostatic anatomical parameters and the severity of LUTS in patients with BPH across different PV categories, and to develop a predictive model for voiding dysfunction based on these anatomical parameters. Methods:This retrospective study included 257 patients with BPH who visited The First Affiliated Hospital of Jinan University for LUTS between January 2023 and March 2024. Transrectal ultrasound was used to measure the PV, IPP, BNA, prostatic urethral angle (PUA), prostatic urethral length (PUL) and other anatomical parameters. Patients were stratified by PV (<30 vs. ≥30 mL). The International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Qmax) were recorded. Prostatic anatomical parameters were correlated with the LUTS severity using Spearman's rank correlation analysis, followed by linear regression modeling to quantify these associations. Predictive models were constructed based on the parameters identified by logistic regression. Receiver operating characteristic (ROC) curves were utilized to determine optimal cutoff values and evaluate model performance. Results:Of 257 patients with BPH, 91 (35.4%) and 166 (64.6%) belonged to the large-volume and small-volume groups, respectively. Multivariable linear regression revealed that, in small prostates, PUL (β=0.20), BNA (β=0.12) and age (β=0.11) independently predicted the International Prostate Symptom Score total score (IPSS-t), whereas PUL (β=-0.29) and BNA (β=-0.09) predicted Qmax. For large prostates, IPP (β=0.29), age (β=0.14), BNA (β=0.09), and PUA (β=0.08) predicted IPSS-t, whereas IPP (β=-0.21) and PUA (β=-0.09) predicted Qmax. Logistic regression demonstrated that the combination of IPP, BNA, and PUA constituted a significant predictor of voiding dysfunction (Qmax <10 mL/s) in patients with large PV. In the large-volume group, the combined model achieved an area under the curve (AUC) of 0.94 [95% confidence interval (CI): 0.90-0.99], which indicated robust discriminative power. Conclusions:Volume-stratified analysis provides a more precise assessment of prostate anatomical parameters in BPH. A model integrating IPP, BNA, and PUA demonstrates favorable accuracy in predicting voiding dysfunction specifically in large‑volume BPH. These findings underscore the clinical utility of ultrasonographic anatomical assessment and support volume‑stratified management. Prospective multicenter validation is required to translate this tool into practice.

Background Bladder cancer is the most common urological malignancy. Bladder cancer has limited therapeutic options, especially in advanced stages. Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a promising target for cancer therapy. However, the role of autophagy in modulating ferroptosis remains incompletely understood.Methods We investigated the anti-tumor effects of JS-K, a nitric oxide-releasing prodrug, in bladder cancer through integrated cell, animal, and patient data studies. In vitro experiments with T24 and UM-UC-3 cells were used to explore how JS-K influences cancer cell survival and the interplay between autophagy and ferroptosis. In vivo, a BALB/c nude mouse tumor model provided a system to examine tumor response and tissue-level changes. To extend these findings to the clinical setting, we analyzed LC3B expression and its associations with ferroptosis-related genes, patient prognosis, and the tumor immune microenvironment.Results JS-K induced mitochondrial damage, lipid peroxidation, reactive oxygen species accumulation, and intracellular iron overload in bladder cancer cells in a concentration-dependent manner. These changes were accompanied by downregulation of GPX4 and SLC7A11 and upregulation of FTH1 and TFR1, indicative of ferroptosis. Inhibition or knockdown of the autophagy marker LC3B reversed these effects, establishing the role of autophagy in mediating ferroptosis. In xenograft models, JS-K suppressed tumor growth, an effect abrogated by LC3B silencing. Integrated transcriptomic and single-cell analyses revealed a strong correlation between LC3B and ferroptosis-related genes, with CISD1 identified as a key prognostic marker.Conclusions JS-K induces autophagy-dependent ferroptosis in bladder cancer cells and significantly suppresses tumor progression. Targeting the autophagy-ferroptosis axis offers a novel therapeutic strategy for bladder cancer treatment.

To determine the predictive value of bladder neck angle (BNA) for trial without catheter (TWOC) following acute urinary retention (AUR) due to benign prostatic obstruction (BPO), and to evaluate its role in predicting response to conservative therapy in patients with lower urinary tract symptoms (LUTS). Outpatients presenting with bothersome LUTS or acute urinary retention (AUR) due to BPO were included in the cohort. The prostate volume, intravesical prostatic protrusion, BNA, and postvoid residual volume were recorded. In patients with AUR, TWOC was performed after 2 weeks of alpha-blocker therapy; those with LUTS received alpha-blockers and 5-alpha reductase inhibitors for 12 months. Surgery was recommended for patients who experienced failure of conservative treatment. The uroflowmetry and International Prostate Symptom Score (IPSS) changes were assessed from baseline to 12 months after treatment. Among 66 patients with AUR, 32 (48.5

Background:Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy associated with limited treatment options and poor prognosis. Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B (ARPC1B), a key regulatory protein within the actin cytoskeleton, could play a pivotal role in ccRCC progression. The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC. Methods:ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis (GEPIA) platform, immunohistochemical (IHC) staining on 150 tumor samples along with 30 corresponding normal tissues, and Western blotting (WB) analyses across multiple ccRCC-derived cell lines. Functional assays assessing cell proliferation, colony formation capability, migration, invasion, and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation. Additionally, WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition (EMT) and the Wnt/β-catenin pathway. Results:The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines, significantly associated with advanced TNM stages, higher Fuhrman grades, and reduced overall survival (OS) (p < 0.001). Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor. Silencing ARPC1B notably impaired ccRCC cellular activities, and tumorigenesis in animal models, whereas augmented ARPC1B expression enhanced these malignant phenotypes. Mechanistically, downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT, indicated by reduced β-catenin, c-Myc, cyclin D1, and ZEB-1 levels, and concurrently increased E-cadherin expression. Additionally, reactivation of the Wnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness. Conclusions:ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway, ultimately enhancing tumor aggressiveness and metastatic potential. Thus, targeting ARPC1B represents a promising therapeutic strategy, warranting further exploration in ccRCC management.

PurposeType 1 diabetes mellitus (T1DM), as an autoimmune disease, can increase susceptibility to clear cell renal cell carcinoma (ccRCC) due to its proinflammatory effects. ccRCC is characterized by its subtle onset and unfavorable prognosis. Thus, the aim of this study was to highlight prevention and early detection opportunities in high-risk populations by identifying common biomarkers for T1DM and ccRCC.MethodsBased on multiple publicly available datasets, WGCNA was applied to identify gene modules closely associated with T1DM, which were then integrated with prognostic DEGs in ccRCC. Subsequently, the LASSO and SVM algorithms were employed to identify shared hub genes between the two diseases. Additionally, clinical samples were used to validate the expression patterns of these hub genes, and scRNA-seq data were utilized to analyze the cell types expressing these genes and to explore potential mechanisms of cell communication.ResultsOverall, three hub genes (KIF21A, PIGH, and RPS6KA2) were identified as shared biomarkers for TIDM and ccRCC. Analysis of clinical samples and multiple datasets revealed that KIF21A and PIGH were significantly downregulated and that PIG was upregulated in the disease group. KIF21A and PIGH are mainly expressed in NK and T cells, PRS6KA2 is mainly expressed in endothelial and epithelial cells, and the MIF signaling pathway may be related to hub genes.ConclusionOur results demonstrated the pivotal roles of hub genes in T1DM and ccRCC. These genes hold promise as novel biomarkers, offering potential avenues for preventive strategies and the development of new precision treatment modalities.

Introduction:The therapeutic efficacy of intravesical agents for bladder cancer (BCa) is frequently constrained by their clearance via urine flushing and periodic bladder emptying, as well as the absence of tumor-targeting capabilities. Consequently, an effective drug delivery system must possess both tumor-targeting and adhesion properties to overcome these limitations. Methods:In this study, we investigated a tumor-selective hydrogel as a potential vehicle for BCa treatment. For the first time in the field of intravesical therapy, we introduced the concept of pre-targeting, sequentially instilling modified polyarginine and membrane nanoparticles into the bladder to achieve selective gelation on the tumor surface. We comprehensively evaluated tumor selectivity, endocytosis pathways, organelle localization, and osmotic capacity, and demonstrated in vivo and in vitro degradation following drug delivery. Results:The pre-targeted hydrogel exhibited superior tumor selectivity. The drug-loaded membrane nanoparticles released during hydrogel degradation were internalized by tumor cells at levels exceeding those in normal cells by more than eightfold. Our findings indicated that this internalization process was energy-dependent and mediated by caveolin. Post-internalization, the drug-loaded membrane nanoparticles localized to the endoplasmic reticulum and Golgi apparatus, with minimal colocalization with lysosomes. Moreover, the hydrogel demonstrated profound penetration into tumor tissue. In terms of antitumor efficacy, the hydrogel loaded with gemcitabine exhibited significantly enhanced therapeutic effects compared to free gemcitabine. Conclusion:Our dual-functional hydrogel system exhibits robust anti-tumor activity against BCa, presenting a promising alternative for intravesical therapy. This innovative approach addresses key limitations of current treatments by combining tumor targeting with sustained drug adhesion, offering a novel strategy for the management of BCa.

Background Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy associated with limited treatment options and poor prognosis. Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B (ARPC1B), a key regulatory protein within the actin cytoskeleton, could play a pivotal role in ccRCC progression. The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC. Methods ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis (GEPIA) platform, immunohistochemical (IHC) staining on 150 tumor samples along with 30 corresponding normal tissues, and Western blotting (WB) analyses across multiple ccRCC-derived cell lines. Functional assays assessing cell proliferation, colony formation capability, migration, invasion, and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation. Additionally, WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition (EMT) and the Wnt/u03B2-catenin pathway. Results The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines, significantly associated with advanced TNM stages, higher Fuhrman grades, and reduced overall survival (OS) (p u0026lt; 0.001). Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor. Silencing ARPC1B notably impaired ccRCC cellular activities, and tumorigenesis in animal models, whereas augmented ARPC1B expression enhanced these malignant phenotypes. Mechanistically, downregulation of ARPC1B suppressed Wnt/u03B2-catenin signaling and disrupted EMT, indicated by reduced u03B2-catenin, c-Myc, cyclin D1, and ZEB-1 levels, and concurrently increased E-cadherin expression. Additionally, reactivation of the Wnt/u03B2-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness. Conclusions ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/u03B2-catenin pathway, ultimately enhancing tumor aggressiveness and metastatic potential. Thus, targeting ARPC1B represents a promising therapeutic strategy, warranting further exploration in ccRCC management.

We conducted a prospective, randomized study to compare the safety and efficacy of using a conventional nephrostomy sheath (CNS) versus a minimally invasive suction-evacuation nephrostomy sheath (SENS) for treating partial staghorn stones. Eighty-six patients with partial staghorn stones were randomly assigned into two groups, with 43 patients in each group. One group underwent standard percutaneous nephrolithotomy (sPCNL) using CNS, whereas the other group underwent minimally invasive percutaneous nephrolithotomy (mPCNL) with SENS. Patient demographics, stone characteristics, intraoperative data, perioperative data, and surgical results were collected and analyzed.The patient demographics and stone characteristics were similar in both groups. The SENS group had significantly lower peak and mean intrarenal pressure (IRP) during the procedure. The stone-free rate (SFR) was comparable between groups. The SENS group removed stones more efficiently, with shorter treatment time and less frequent use of the stone extractor. Lower IRP and shorter treatment time led to fewer postoperative complications.mPCNL with SENS results in lower IRP, faster stone removal, and reduced use of stone forceps while preserving SFR and safety.

Chemokines influence the progression of prostate cancer (PCa) through multiple mechanisms. However, the effect of C-X3-C chemokine ligand 1 (CX3CL1) on PCa risk remains controversial. Our study aimed to investigate whether circulating CX3CL1 is causally associated with PCa and to identify metabolites that have mediating effects using the 2-step bidirectional Mendelian randomization (MR) analysis process. Inverse variance weighting (IVW) results were used as the primary observations, while additional sensitivity analyses were conducted. For each standard deviation increase exhibited by the circulating CX3CL1 levels, the risk of PCa was reduced by 0.4% (IVW: OR = 0.996, [95% CI = 0.994-0.998], P < .001), and blood alliin levels increased by 19% (IVW: OR = 1.185, [95% CI = 1.01-1.54], P = .003). For each standard deviation increase in the blood alliin levels, the risk of PCa was reduced by 0.1% (IVW: OR = 0.999, [95% CI = 0.997-0.999], P = .03). Therefore, the protective effect of circulating CX3CL1 on PCa may be mediated by blood alliin levels (mediated proportion = 6.7%). The results supported the notion that high levels of circulating CX3CL1 indicate a lower PCa risk and the idea that the food-derived antioxidant alliin may mediate this association. We emphasize that the use of CX3CL1 as a protective factor against PCa may provide new strategies for PCa prevention and care in the future.

BACKGROUND:Non-obstructive azoospermia is the most severe form of male infertility. A testicular biopsy is required for the diagnosis of non-obstructive azoospermia, and the causal factors for non-obstructive azoospermia remain unknown. OBJECTIVES:To reduce the risk of multiple biopsies and identify factors that contribute to non-obstructive azoospermia, we proposed an integrated approach for the preoperative diagnosis and clinical management of non-obstructive azoospermia by applying the chromosome-spreading technique and whole-exome sequencing. MATERIALS AND METHODS:Between July 2020 and December 2022, after ruling out definitive obstructive azoospermia and non-obstructive azoospermia patients with testicular volume < 6 mL, 20 patients with non-obstructive azoospermia who underwent preoperative testicular diagnostic biopsy using testicular sperm aspiration were subjected to retrospective analysis. RESULTS:Microscopic examination identified four patients with sperm cells, and 16 without sperm cells. Routine pathological analysis classified one patient as normal spermatogenesis, three as hypospermatogenesis, five as maturation arrest, nine as Sertoli cell-only, and two as unable to judge. With chromosome-spreading technology using routine cell suspension samples for microscopic examination, 18 patient diagnoses were validated, and two patients without a definitive diagnosis were supplemented. Detection of the Y chromosome and a well-organized whole-exome sequencing analysis revealed potential genetic factors. DISCUSSION AND CONCLUSION:The full use of testicular biopsy is beneficial for the diagnosis of azoospermia, as it avoids the risk of multiple biopsies. Moreover, in combination with whole-exome sequencing, clinicians can obtain more information regarding the pathogenesis of non-obstructive azoospermia, which may guide treatment.

Objective:To investigate the strategy, technique and short-term efficacy of partial clamping of the suprahepatic inferior vena cava (IVC) and aspiration of thrombus without median sternotomy and cardiopulmonary bypass under total 3D laparoscopy, combination with left radical nephrectomy in the treatment of left renal cell carcinoma with level Ⅳ IVC thrombus.Methods:The data of 54-year-old male patient in the First Affiliated Hospital of Jinan University with left renal tumor and level Ⅳ IVC thrombus was collected, the upper border of the thrombus of the patient reaching to the entrance of the right atrium (Mayo Ⅳ). Left renal artery embolization was performed one day before operation. On the day of operation, after the preparation for cardiopulmonary bypass, the patient was placed in the 70° right lateral decubitus supine position, clamped the suprahepatic IVC partially and extracted the thrombus successfully under Storz 3D laparoscopy. The whole process of extracting thrombus was monitored by transesophageal ultrasound. Then the posture was changed to 70° left lateral decubitus supine position for radical left nephrectomy and left retroperitoneal lymphatic dissection.Results:The operation was completed successfully with an operative time of 530 min, the intraoperative blood loss was 450 ml.The patient recovered smoothly and was discharged one week later. In addition, the patients received anticoagulation for three months and adjuvant targeted therapy. Imaging examination showed that there was no tumor recurrence in the thirteen months follow-up.Conclusions:The method of complete laparoscopic partial blockade of the inferior hepatic vena cava and thrombus aspiration without extracorporeal circulation and open chest is minimally invasive and feasible for some of the level Ⅳ IVC thrombus which are small and free. It could reduce the possible complications caused by open chest and extracorporeal bypass and help patients recover quickly, but more cases and longer-term follow-up are needed to confirm its efficacy.

To assess the safety and effectiveness of the 4.5/6.5 Fr ureteroscopic laser lithotripsy (URSL) under topical intraurethral anesthesia (TIUA) compared to spinal anesthesia (SA). A retrospective study was conducted on 47 (TIUA: SA = 23:24) patients receiving 4.5/6.5 Fr URSL from July 2022 to September 2022. For the TIUA group, atropine, pethidine, and phloroglucinol were used apart from lidocaine. In the SA group, patients received lidocaine and bupivacaine. We compare the two groups including stone-free rate (SFR), procedure time, anesthesia time, overall operative time, hospital stay, anesthesia failure, intraoperative pain, need for additional analgesia, cost, and complications. The conversion rate in the TIUA group was 4.35% (1/23). SFR was 100% in both groups. Surgical waiting time and anesthesia time were longer in the SA group (P < 0.001). There were no statistical differences in operational time and intraoperative pain. Patients developed grade 0–1 ureteral injuries. Post-surgical time out of bed was noticeably faster in the TIUA group (P < 0.001). The post-operative complication rate including vomiting and back pain was lower in the TIUA group (P = 0.005). TIUA had an equal surgical success rate and controlled patients’ intraoperative pain as SA. It was superior in terms of TIUA’s patient admission, waiting time for surgery, anesthesia time, post-operative time out of bed, low complications, and costs, especially for females.

BACKGROUND:Castration-resistant prostate cancer (CRPC) inevitably arises after androgen deprivation therapy (ADT). Therefore, there is an urgent need to search for novel treatment strategies for CRPC. Polyphyllin I (PPI), one of the steroidal saponins in paris polyphylla, has been shown to have an anticancer effect. This study investigated the role and mechanism of PPI in CRPC cell ferroptosis. METHODS:Protein levels of GPX4, p-extracellular regulated protein kinases (ERK), ERK, DNMT1, and ACSL4 were measured by Western blot. DNMT1 and ACSL4 mRNA expression was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Prostate cancer cells (DU145, PC3) were treated with PPI. Cell viability was assessed utilizing Cell Counting Kit-8 (CCK-8) assay. The role of PPI in regulating ferroptosis was determined by analyzing lipid reactive oxygen species (ROS), malonyl dialdehyde (MDA), iron (Fe2+ ), and glutathione (GSH) content. Chromatin immunoprecipitation (ChIP) assay verified the effect of DNMT1 on the ACSL4 promoter. The methylation level of ACSL4 promoter was assessed utilizing MSP. A nude mice xenograft was adopted to detect the effect of PPI in vivo. RESULTS:PPI inhibited CRPC cell proliferation, reduced levels of GSH and GPX4, and increased levels of MDA, Fe2+ , and ROS, while ERK inhibitor reversed the effect of PPI on ferroptosis. PPI repressed the methylation level of ACSL4 promoter by inhibiting DNMT1. DNMT1 knockdown promoted CRPC cell ferroptosis by regulating ACSL4. PPI induced ferroptosis and suppressed CRPC growth in nude mice. CONCLUSION:PPI can be used as a ferroptosis inducer to induce ferroptosis in CRPC cells via the ERK/DNMT1/ACSL4 axis, suggesting that PPI may be a new strategy for CRPC treatment.

IntroductionRadical cystectomy with dissection of pelvic lymph nodes and urethral diversion is the standard surgical treatment for muscle-invasive non-metastatic bladder cancer. In rare cases where patients with bladder cancer without distant metastasis have pelvic multi-organ invasion, the cancer compresses or invades the ureter and, in severe cases, leads to bilateral upper urinary tract obstruction and renal damage. The treatment recommended by guidelines often cannot improve the patients’ clinical symptoms immediately, and patients cannot complete the treatment owing to severe side effects, resulting in poor survival benefits.Case presentationA 69-year-old woman with facial edema was treated at the First Affiliated Hospital of Jinan University. The serum creatinine and potassium values were 1244 umol/L and 5.86 mmol/L, respectively. Pelvic magnetic resonance and abdominal computed tomography revealed that the bladder tumor had infiltrated the uterus, anterior vaginal wall, rectum, right ureter, right fallopian tube, and right ovary and metastasized to multiple pelvic lymph nodes. Tumor invasion of the right ureter resulted in severe hydronephrosis of the right kidney and loss of function and obstructive symptoms in the left kidney. Four days later, the patient’s creatinine level decreased to 98 u mol/L, the general condition significantly improved, and the patient and family members strongly desired surgical treatment of the tumor. Through a comprehensive preoperative discussion, possible intraoperative and postoperative complications were evaluated. Right nephrectomy, right ureterectomy, total pelvic organ resection, extended pelvic lymph node dissection, and bowel and urinary diversion were conducted under 3D laparoscopy-assisted treatment. The patient was followed-up for 1.5 years and showed good tumor control, self-care, and mental status.ConclusionMinimally invasive surgery is a curative option for patients with bladder cancer with pelvic multi-organ invasion without distant metastasis. Surgeons should strictly control the indications for surgery and warn patients about the occurrence of related post-surgical complications.

Objective:To explore the application value of transrectal ultrasound images classification network model of prostate cancer based on deep learning in the classification of benign and malignant prostate tissue in transrectal ultrasound images.Methods:A total of 1 462 two-dimensional images of transrectal prostate biopsy with clear pathologic results(including 658 images of malignant tumor, 804 images of benign tumor) from 203 patients with suspicious prostate cancer(including 89 cases of malignant tumor, 114 cases of benign tumor) were collected from May 2018 to May 2021 in the First Affiliated Hospital of Jinan University. They were divided into the training database, validation database, and test database. And the training and validation database were used to train and obtain the intelligence-assisted diagnosis network model, and then the test database was used to test the network model and two ultrasound doctors of different ages. With pathologic diagnosis as the gold standard, the diagnostic performance among them was evaluated.Results:①The sensitivity of network model was 66.7% the specificity was 91.9%, the accuracy was 80.5%, the precision(positive predictive value) was 87.1%. The area under the ROC curve was 0.922. ②The accuracy of the junior and senior ultrasound doctors was 57.5%, 62.0%; the specificity was 62.0%, 66.3%; the sensitivity was 51.5%, 56.8%; the precision was 53.1%, 58.1%, respectively. ③The accuracy, sensitivity, specificity, precision of classification: the network model > the ultrasound doctors, the differences were significant( P<0.05); the senior ultrasound doctor>the junior ultrasound doctor, the differences were not significant( P>0.05). Conclusions:The intelligence-assisted diagnosis network model based on deep learning can classify benign and malignant prostate tissue in transrectal ultrasound images, improve the accuracy of ultrasound doctors in diagnosing prostate cancer. It is of great significance to improve the efficiency of screening for patients with high clinical suspicion of prostate cancer.

前列腺癌（prostate cancer，PCa）是欧美地区男性发病率及死亡率均排第二位的恶性肿瘤[1]。近年来我国PCa发病率及死亡率呈逐年增长趋势[2]。研究发现PCa转移是导致患者预后较差的重要因素[3]。众所周知，转移性PCa中以淋巴结转移最为常见。盆腔淋巴结清扫（pelvic lymph node dissection，PLND）是诊断PCa淋巴结转移的"金标准"，但目前PLND的适应证、范围和患者获益程度仍存在较大争议[4]。术前明确诊断PCa淋巴结转移有助于患者准确地分期及选择最佳的治疗方案。如何在前列腺癌根治术（radical prostatectomy，RP）前准确判断是否有淋巴结转移及转移范围是临床工作中的重点和难点。前列腺特异性抗原（prostate specific antigen，PSA）、Gleason评分、临床分期、前列腺穿刺阳性针数及其百分比、前列腺特异性抗原密度（PSA density，PSAD）、前列腺健康指数（prostate health index，PHI）、体质量指数（body mass index，BMI）、多参数磁共振成像（multiparametric magnetic resonance Imaging，mpMRI）、前列腺影像和数据系统（prostate imaging reporting and data system，PI-RADS）评分、前列腺特异性膜抗原正电子发射断层扫描成像（prostate-specific membrane antigen positron-emission tomography，PSMA PET-CT）等临床指标；MSKCC、Briganti 2012、Partin 2016、Yale、Briganti 2017和Briganti 2019等列线图模型；17-gene Oncotype DX前列腺基因组评分（genomic prostate score，GPS）、塌陷反应调节蛋白4（collapsin response mediator proteins，CRMP4）甲基化、99mTc硫胶体、光学示踪剂如吲哚菁绿（indocyanine green，ICG）、混合示踪剂等新技术均在预测PCa淋巴结转移中有相关报道。本研究系统总结了术前预测PCa淋巴结转移的各种参数及其进展。

Background:This study determined the predictive value of CRMP4 promoter methylation in prostate tissues collected by core needle biopsies for a postoperative upgrade of Gleason Score (GS) to ≥8 in patients with low-risk PCa. Method:A retrospective analysis of the clinical data was conducted from 631 patients diagnosed with low-risk PCa by core needle biopsy at multiple centers and then underwent Radical Prostatectomy (RP) from 2014-2019. Specimens were collected by core needle biopsy to detect CRMP4 promoter methylation. The pathologic factors correlated with the postoperative GS upgrade to ≥8 were analyzed by logistic regression. The cut-off value for CRMP4 promoter methylation in the prostate tissues collected by core needle biopsy was estimated from the ROC curve in patients with a postoperative GS upgrade to ≥8. Result:Multivariate logistic regression showed that prostate volume, number of positive cores, and CRMP4 promoter methylation were predictive factors for a GS upgrade to ≥8 (OR: 0.94, 95% CI: 0.91-0.98, P=0.003; OR: 3.16, 95% CI: 1.81-5.53, P<0.001; and OR: 1.43, 95% CI: 1.32-1.55, P<0.001, respectively). The positive predictive rate was 85.2%, the negative predictive rate was 99.3%, and the overall predictive rate was 97.9%. When the CRMP4 promoter methylation rate was >18.00%, the low-risk PCa patients were more likely to escalate to high-risk patients. The predictive sensitivity and specificity were 86.9% and 98.8%, respectively. The area under the ROC curve (AUC) was 0.929 (95% CI: 0.883-0.976; P<0.001). The biochemical recurrence (BCR)-free survival, progression-free survival (PFS), and cancer-specific survival (CSS) were worse in patients with CRMP4 methylation >18.0% and postoperative GS upgrade to ≥8 than in patients without an upgrade (P ≤ 0.002). Conclusion:A CRMP4 promoter methylation rate >18.00% in prostate cancer tissues indicated that patients were more likely to escalate from low-to-high risk after undergoing an RP. We recommend determining CRMP4 promoter methylation before RP for low-risk PCa patients.

Clear cell renal cell carcinoma (ccRCC) accounts for 80% of renal cell carcinomas (RCCs), and its morbidity and prognosis are unfavorable. Surgical resection is the first-line treatment for ccRCC, but the oncogenesis of ccRCC is very complex. With the development of high-throughput sequencing technology, it is necessary to analyze the transcriptome to determine more effective treatment methods. The tumor microenvironment (TME) is composed of tumor cells, various immune-infiltrating cells, fibroblasts, many cytokines, and catalysts. It is a complex system with a dynamic balance that plays an essential role in tumor growth, invasion, and metastasis. Previous studies have confirmed that potassium channels can affect the immune system, especially T lymphocytes that require potassium channel activation. However, the effect of potassium channels on the TME of ccRCC remains to be studied. Therefore, this study aims to construct a prognostic signature for ccRCC patients based on potassium ion channel-related genes (PCRGs), assess patient risk scores, and divide patients into high- and low-risk groups based on the cutoff value. In addition, we investigated whether there were differences in immune cell infiltration, immune activator expression, somatic mutations, and chemotherapeutic responses between the high- and low-risk groups. Our results demonstrate that the PCRG signature can accurately assess patient prognosis and the tumor microenvironment and predict chemotherapeutic responses. In summary, the PCRG signature could serve as an auxiliary tool for the precision treatment of ccRCC.

ObjectivesClear cell renal cell carcinoma (ccRCC) is highly prevalent, prone to metastasis, and has a poor prognosis after metastasis. Therefore, this study aimed to develop a prognostic model to predict the individualized prognosis of patients with metastatic clear cell renal cell carcinoma (mccRCC).Patients and MethodsData of 1790 patients with mccRCC, registered from 2010 to 2015, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. The included patients were randomly divided into a training set (n = 1253) and a validation set (n = 537) based on the ratio of 7:3. The univariate and multivariate Cox regression analyses were used to identify the important independent prognostic factors. A nomogram was then constructed to predict cancer specific survival (CSS). The performance of the nomogram was internally validated by using the concordance index (C-index), calibration plots, receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). We compared the nomogram with the TNM staging system. Kaplan–Meier survival analysis was applied to validate the application of the risk stratification system.ResultsDiagnostic age, T-stage, N-stage, bone metastases, brain metastases, liver metastases, lung metastases, chemotherapy, radiotherapy, surgery, and histological grade were identified as independent predictors of CSS. The C-index of training and validation sets are 0.707 and 0.650 respectively. In the training set, the AUC of CSS predicted by nomogram in patients with mccRCC at 1-, 3- and 5-years were 0.770, 0.758, and 0.757, respectively. And that in the validation set were 0.717, 0.700, and 0.700 respectively. Calibration plots also showed great prediction accuracy. Compared with the TNM staging system, NRI and IDI results showed that the predictive ability of the nomogram was greatly improved, and DCA showed that patients obtained clinical benefits. The risk stratification system can significantly distinguish the patients with different survival risks.ConclusionIn this study, we developed and validated a nomogram to predict the CSS rate in patients with mccRCC. It showed consistent reliability and clinical applicability. Nomogram may assist clinicians in evaluating the risk factors of patients and formulating an optimal individualized treatment strategy.