Perioperative care based on roy adaptation model in elderly patients with benign prostatic hyperplasia: impact on psychological well-being, pain, and quality of life.

PURPOSE: This study aimed to assess the impact of perioperative care based on the Roy Adaptation Model (RAM) on psychological well-being, postoperative pain, and health-related quality of life (HRQoL) in elderly patients with benign prostatic hyperplasia (BPH) undergoing transurethral resection of the prostate (TURP). METHODS: A total of 160 elderly patients diagnosed with BPH between June 2021 and June 2022 and scheduled for TURP were randomly assigned to either the routine care group (n = 80) or the RAM group (n = 80). The RAM group received standard care supplemented with interventions based on the RAM model. Negative emotions measured by the Hospital Anxiety and Depression Scale (HADS), pain intensity by the Visual Analog Scale (VAS), and HRQoL by the 36-Item Short Form Health Survey (SF-36) were measured at the preoperative visit (T0), at 30 days (T1), and at 3 months of (T2) follow­up. RESULTS: Repeated measures ANOVA revealed significant differences in psychological well-being, postoperative pain intensity, and HRQoL within both the routine care and RAM groups across the three time points. Holm-Sidak's multiple comparisons test confirmed significant differences between each time point for both groups. The RAM intervention led to significant reductions in anxiety and depression levels, alleviation of postoperative pain intensity, and improvements in various domains of HRQoL at T1 and T2 compared to routine care. CONCLUSION: Incorporating the RAM model into perioperative care for elderly patients undergoing TURP for BPH has shown promising results in improving psychological well-being, reducing postoperative pain intensity, and enhancing HRQoL.

Comparison of two techniques for the management of 2-3 cm lower pole renal calculi in obese patients.

OBJECTIVE: To compare the outcomes of mini percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) for the management of 2-3 cm lower pole renal calculi (LPC) in obese patients. PATIENTS AND METHODS: 120 obese patients with 2-3 cm LPC were randomly divided into mPNL group and RIRS group. Demography, clinical characteristics, perioperative complications, and stone free rate (SFR) were recorded. Stone-free status means no stone on computed tomography 3 months after surgery, or residual fragments were less than 3 mm. RESULTS: Baseline characteristics were similar between the two groups. The mean stone burden was 585.39 ± 131.06 mm2 in the mPNL group and 548.64 ± 123.55 mm2 in the RIRS group (P = 0.125). The SFR of mPNL group was significantly better than that of RIRS group (86.2% vs 61.4%, P = 0.002). Besides, the overall complication rate was 22.4% in the mPNL group and 7% in the RIRS group (P = 0.02). Patients performed with mPNL required longer length of hospital stay than those with RIRS (P = 0.001). There were no significant differences in operative time and stone composition between the two groups. CONCLUSION: In our study, both mPNL and RIRS are safe and effective techniques for the treatment of 2-3 cm LPC in obese patients. Compared to RIRS, mPNL has better SFR at the expense of the higher incidence of complications and prolonged length of hospital stay.

Expression profiles, biological functions and clinical significance of circRNAs in bladder cancer.

Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5' caps and 3' poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients' survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.

Comparison of contrast-enhanced ultrasound versus conventional ultrasound-guided percutaneous nephrolithotomy in patients with nondilated collecting system: a randomized controlled trial.

OBJECTIVE: To compare the safety, effectiveness, and feasibility of contrast-enhanced ultrasound (CEUS) versus conventional ultrasound-guided percutaneous nephrolithotomy (PCNL) in patients with nondilated collecting system. METHODS: Between July 2018 and July 2020, 160 kidney stone patients with nondilated collecting system planned for PCNL were randomly assigned into two groups, CEUS with retrograde ureteral contrast injection and conventional ultrasound with retrograde ureteral normal saline injection. Patient's demographics, the success rate of puncture, success rate of a single-needle puncture, number of punctures, puncture time, perioperative outcomes, stone-free rate, and incidence of complications were compared. RESULTS: The success rate of a single-needle puncture for CEUS-guided PCNL was higher than that in the conventional ultrasound group (88.5% vs. 73.7%, p = 0.02). Patients performed with CEUS-guided PCNL required less needle passes (p = 0.02), shorter needle puncture time (p = 0.031), and shorter channel establishment time (p = 0.04) than those guided with conventional ultrasound. The postoperative hemoglobin decrease in the CEUS-guided PCNL group was less than that of the control group (p = 0.02). There was no significant difference in operating time, length of hospital stays, kidney function change, and complications between the two groups (p > 0.05). The 1-month stone-free rate was 94.9% in the CEUS group and 90.8% in the control group (p > 0.05). CONCLUSIONS: Compared with conventional ultrasound, CEUS-guided PCNL may facilitate ultrasound-guided PCNL for patients without hydronephrosis, and benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800016981 KEY POINTS: • Compared with conventional ultrasound, CEUS-guided PCNL is a safe and efficacious procedure for kidney stone patients with nondilated collecting system. • Compared with conventional ultrasound, CEUS-guided PCNL benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. • CEUS-guided PCNL associated with the more accurate needle puncture and acceptable complications.

Mini-Percutaneous Nephrolithotomy with Ureter Catheter: A Safe and Effective form of mPCNL Offers Better Quality of Life.

OBJECTIVE: To compare outcomes and postoperative quality of life (QoL) among patients with kidney stone who received mini-percutaneous nephrolithotomy (mPCNL), partial tubeless mPCNL or mPCNL with ureter catheter in a prospective randomized clinical trial. METHODS: From May 2017 to December 2017, 60 patients with kidney stone who underwent mPCNL were randomized into 3 groups: Group I (mPCNL), Group II (partial tubeless mPCNL), Group III (mPCNL with ureter catheter). We evaluated perioperative characteristics, stone clearance, analgesic requirements and QoL by using the Wisconsin Stone QOL questionnaire. RESULTS: The age, gender, stone diameter, body mass index, length of operation, drop in hemoglobin and stone-free rates for the 3 groups were similar among these groups. However, the postoperative visual analog scale and the analgesic requirement in Group II were significantly the lowest (p < 0.05). According to Wisconsin Stone QOL questionnaire, compared to Group I, statistical significant difference in the QoL was seen in Group II and III, indicating a meaningful and immediate improvement in the postoperative QoL following mPCNL. CONCLUSION: Compared with standard and partial tubeless mPCNL, mPCNL with ureter catheter is a safe and useful form of mPCNL, which can offer better QoL and is more cost effective.

Usage of Multilevel Paravertebral Block as the Main Anesthesia for Mini-Invasive PCNL: Retrospective Review of 45 Cases with Large Stones.

INTRODUCTION: To evaluate the efficiency and safety of the paravertebral block (PVB) as the single main anesthesia for unilateral mini-invasive percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: Forty-five American Society of Anesthesiologists grade I/II/III patients with large upper urinary tract stones were included in our retrospective study. All patients received multilevel PVB from T10 to L1 with 10 mL of 0.5% ropivacaine for each segment. After the block was confirmed, unilateral mini-invasive PCNL was performed. Intraoperative and postoperative pain management and associated adverse events were observed to investigate the feasibility of PVB in mini-invasive PCNL as the main anesthesia. RESULTS: Successful blocking was confirmed 20 min after paravertebral injections. The mean operation time was 59 min. None of the patients experienced severe pain or hemodynamic dysfunction. Stone-free rate was 93.1% and no blood transfusion was required. The mean time to first analgesic requirement was 160 min, and the mean consumption of diclofenac sodium suppositories was 150 mg. All patients contained normal muscle strength on the contralateral side. Patients could recover ambulation within 1 h after the operation. CONCLUSIONS: Multilevel PVB was proved to be suitable as the main anesthesia for unilateral mini-invasive PCNL, providing feasible pain relief and quick postoperative recovery.

Evaluation of a large adrenal carcinoma with 3D reconstruction of computed tomography images: A case report and literature review.

Adrenocortical carcinoma (ACC) is an extremely rare disease caused by a cancerous growth in the adrenal cortex. Although most of adrenal tumors are benign, the functional ACC is malignant resulting in endocrine dysfunction and necessitates surgical removal. Retroperitoneal laparoscope adrenalectomy is often used to perform adrenal gland surgery. Here, we reported a case of huge ACC with the size of 6.8 cm × 5.2 cm. To achieve better surgical outcome, we integrated 3D reconstructed CT images into a dynamic video for preoperative planning and intraoperative guiding to resect the diseased adrenal gland completely without neighbor organ's injury and surgery complications. Moreover, we reviewed associated applications using 3D reconstructed CT imaging in surgery field. Finally, the evaluation and effect of such technology were discussed to reveal that the 3D dynamic video can help surgeon to make better preoperative assessment so as to give patients better therapy.

The Application of Nanoparticles Targeting Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.

The role of circular RNA in tumor microenvironment and immunotherapy.

Cancer immunotherapy has favorable efficacy in various types of tumors, and has become an important weapon in the treatment of tumors in recent years. Long noncoding RNAs and microRNAs have been identified to play important roles in regulating cancer immunotherapy. Circular RNAs (circRNAs) are involved in the pathological process of many diseases, especially cancer. Many functions of circRNAs have been extensively studied. However, the functions of circRNAs in the tumor microenvironment and cancer immunotherapy do not appear to be fully elucidated. Therefore, we review the roles of circRNAs in tumor microenvironment and cancer immunotherapy.

Predictive value of CD3+ cells and interleukin 2 receptor in systemic inflammatory response syndrome after percutaneous nephrolithotomy.

Objective: The aim of the current study was to evaluate the risk factors that influence the development of postoperative systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL), including cytokines and lymphocyte subsets. Methods: A total of 154 patients who underwent PCNL at our hospital between October 2019 and January 2022 were retrospectively reviewed. The development of post-PCNL SIRS was the primary endpoint of the study. Univariable analysis and multivariable logistic regression analysis were performed to identify independent risk factors of post-PCNL SIRS. A nomogram was constructed using the independent risk factors, and receiver operating characteristic (ROC) curves were drawn. Results: There were 50 patients (32.5%) who developed SIRS after PCNL. In multivariate analysis, positive urine culture (odds ratio [OR], 3.556; p = 0.048), long operation time (OR, 1.011; p = 0.027), high IL-2R (OR, 1.002; p = 0.018), low percentage of CD3+ cells (OR 0.931; p = 0.006), and high white blood cell (WBC) count (OR, 1.282; p = 0.044) were independent risk factors for post-PCNL SIRS. These five significant variables were used to generate a nomogram that exhibited favorable fitting. The discrimination area under the ROC curves was 0.795. Conclusions: Patients with long operation times, positive urine cultures, high interleukin 2 receptor, high white blood cell counts, and low percentages of CD3+ cells may be at a higher risk of developing SIRS after PCNL. In these patients, cautious and comprehensive preoperative evaluations and appropriate treatment strategies should be considered.

VEGF pathway-targeted therapy for advanced renal cell carcinoma: a meta-analysis of randomized controlled trials.

Immunotherapy which has been in practice for more than 20 years proves effective for the treatment of metastatic renal cell carcinoma (mRCC). Anti-angiogenesis-targeted therapy has recently been identified as a promising therapeutic strategy for mRCC. This study was aimed to evaluate the effectiveness of vascular endothelial growth factor (VEGF) pathway-targeted therapy for mRCC by comparing its effectiveness with that of immunotherapy. The electronic databases were searched. Randomized controlled trials (RCTs) on comparison of VEGF inhibiting drugs (sorafenib, sunitinib and bevacizumab) with interferon (IFN) or placebo for mRCC treatment were included. Data were pooled to meta-analyze. A total of 7 RCTs with 3451 patients were involved. The results showed that anti-VEGF agents improved progression-free survival (PFS) and offered substantial clinical benefits to patients with mRCC. Among them, sunitinib had a higher overall response rate (ORR) than IFN (47% versus 12%, P<0.000001). Bevacizumab plus IFN produced a superior PFS [risk ratio (RR): 0.86, 95% confidence interval (CI): 0.76-0.97; P=0.01] and ORR (RR: 2.19; 95% CI: 1.72-2.78; P<0.00001) in patients with mRCC over IFN, but it yielded an increase by 31% in the risk of serious toxic effects (RR: 1.31; 95% CI: 1.20-1.43; P<0.00001) as compared with IFN. The overall survival (OS) was extended by sorafenib (17.8 months) and sunitinib (26.4 months) as compared with IFN (13 months). It was concluded that compared with IFN therapy, VEGF pathway-targeted therapies improved PFS and achieved significant therapeutic benefits in mRCC. However, the risk to benefit ratio of these agents needs to be further evaluated.

Retroperitoneoscopic nephrectomy versus open surgery for non-tuberculous pyonephrotic nonfunctioning kidney: a single-center experience.

BACKGROUND: Patients with obstructive pyonephrotic nonfunctioning kidney (OPNK) often require simple nephrectomy for long-term severe clinical symptoms. We aimed to analyze the outcomes of retroperitoneal laparoscopy versus open surgery for OPNK. METHODS: The study included clinical data of 69 patients with non-tuberculous OPNK from January 2015 to June 2019 in a single center. The patients were divided into laparoscopic group (LS, N=33) and open surgery group (OS, N=36). Those whose pathological findings were xanthogranulomatous inflammation or tuberculous granuloma were excluded. Statistical analysis compared the two groups in terms of basic demographic characteristics, preoperative laboratory examination results, and intraoperative and postoperative observation indicators. RESULTS: The results showed that non-tuberculous OPNK were more common in women (female/male =4:1). Compared with the LS group, patients in the OS group had higher white blood cells (WBC; P=0.010) and neutrophils (P=0.005) counts before surgery. The main clinical symptoms were low back pain, pyuria, and fever; among them, low back pain combined with pyuria was in the majority. More intraoperative hypotension events were observed in the OS group (P=0.007). Notably, subgroup analysis showed larger stone size happened in the OS group (OR 3.538, 95% CI, 1.337, 9.208). No statistical difference was found in the duration of surgery between the two groups while the length of postoperative hospitalization and retroperitoneal drainage, and postoperative blood transfusion rate increased significantly in the OS group. Postoperative use of non-steroidal anti-inflammatory drugs was more common in the LS group, while opioid analgesics were in the OS group (P=0.0006). There was no statistical difference in other complications. CONCLUSIONS: In conclusion, considering the advantages of LS in terms of postoperative blood transfusion, surgical drainage and length of hospital stay, we recommend it for non-tubercular OPNK when the stone load of pyonephrosis side was less than 280 mm2 and the preoperative WBC and neutrophil count were within the normal range.

Added Value of Systemic Inflammation Markers in Predicting Clinical Stage T1 Renal Cell Carcinoma Pathologically Upstaged to T3a.

OBJECTIVES: We aimed to determine preoperative risk factors associated with pathologic T3a (pT3a) upstaging of clinical T1 (cT1) renal cell carcinomas (RCCs) and develop a novel model capable of accurately identifying those patients at high risk of harboring occult pT3a characteristics. METHODS: A retrospective analysis of 1324 cT1 RCC patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) was performed. The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. Univariable and multivariable logistic regression analyses were performed to identify predictors associated with cT1 to pT3a upstaging and subsequently, those significant risk factors were used to construct models. We used the area under the curve (AUC) to determine the model with the highest discrimination power. Decision curve analyses (DCAs) were applied to evaluate clinical net benefit associated with using the predictive models. RESULTS: The rates of upstaging were 6.1% (n = 81), 5.8% (n = 54) and 6.8% (n = 27) in the total population, training cohort and validation cohort, respectively. Tumor size, clinical T stage, R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior) nephrometry score, lymphocyte to monocyte ratio (LMR), prognostic nutrition index (PNI) and albumin to globulin ratio (AGR) were significantly associated with pT3a upstaging. The model that consisted of R.E.N.A.L. score, LMR, AGR and PNI achieved the highest AUC of 0.70 in the validation cohort and yielded the highest net benefit. In the subpopulation with complete serum lipid profile, the inclusion of low-density lipoprotein cholesterol (LDL-C) and Castelli risk index-I (CRI-I) significantly improved the discrimination of model (AUC = 0.86). CONCLUSIONS: Our finding highlights the importance of systemic inflammation response markers and serum lipid parameters in predicting pT3a upstaging. Our model had relatively good discrimination in predicting occult pT3a disease among patients with cT1 renal lesions, and the use of the model may be greatly beneficial to urologists in risk stratification and management decisions.

Machine learning-assisted decision-support models to better predict patients with calculous pyonephrosis.

BACKGROUND: To develop a machine learning (ML)-assisted model capable of accurately identifying patients with calculous pyonephrosis before making treatment decisions by integrating multiple clinical characteristics. METHODS: We retrospectively collected data from patients with obstructed hydronephrosis who underwent retrograde ureteral stent insertion, percutaneous nephrostomy (PCN), or percutaneous nephrolithotomy (PCNL). The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. We developed 5 ML-assisted models from 22 clinical features using logistic regression (LR), LR optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), support vector machine (SVM), extreme gradient boosting (XGBoost), and random forest (RF). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Decision curve analysis (DCA) was used to investigate the clinical net benefit associated with using the predictive models. RESULTS: A total of 322 patients were included, with 225 patients in the training dataset, and 97 patients in the testing dataset. The XGBoost model showed good discrimination with the AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.981, 0.991, 0.962, 1.000, 1.000, and 0.989, respectively, followed by SVM [AUC =0.985, 95% confidence interval (CI): 0.970-1.000], Lasso-LR (AUC =0.977, 95% CI: 0.958-0.996), LR (AUC =0.936, 95% CI: 0.905-0.968), and RF (AUC =0.920, 95% CI: 0.870-0.970). Validation of the model showed that SVM yielded the highest AUC (0.977, 95% CI: 0.952-1.000), followed by Lasso-LR (AUC =0.959, 95% CI: 0.921-0.997), XGBoost (AUC =0.958, 95% CI: 0.902-1.000), LR (AUC =0.932, 95% CI: 0.878-0.987), and RF (AUC =0.868, 95% CI: 0.779-0.958) in the testing dataset. CONCLUSIONS: Our ML-based models had good discrimination in predicting patients with obstructed hydronephrosis at high risk of harboring pyonephrosis, and the use of these models may be greatly beneficial to urologists in treatment planning, patient selection, and decision-making.

Theaflavin protects against oxalate calcium-induced kidney oxidative stress injury via upregulation of SIRT1.

Renal tubular cell injury induced by calcium oxalate (CaOx) is a critical initial stage of kidney stone formation. Theaflavin (TF) has been known for its strong antioxidative capacity; however, the effect and molecular mechanism of TF against oxidative stress and injury caused by CaOx crystal exposure in kidneys remains unknown. To explore the potential function of TF on renal crystal deposition and its underlying mechanisms, experiments were conducted using a CaOx nephrocalcinosis mouse model established by glyoxylate intraperitoneal injection, and HK-2 cells were subjected to calcium oxalate monohydrate (COM) crystals, with or without the treatment of TF. We discovered that TF treatment remarkably protected against CaOx-induced kidney oxidative stress injury and reduced crystal deposition. Additionally, miR-128-3p expression was decreased and negatively correlated with SIRT1 level in mouse CaOx nephrocalcinosis model following TF treatment. Moreover, TF suppressed miR-128-3p expression and further abolished its inhibition on SIRT1 to attenuate oxidative stress in vitro. Mechanistically, TF interacted with miR-128-3p and suppressed its expression. In addition, miR-128-3p inhibited SIRT1 expression by directly binding its 3'-untranslated region (UTR). Furthermore, miR-128-3p activation partially reversed the acceerative effect of TF on SIRT1 expression. Taken together, TF exhibits a strong nephroprotective ability to suppress CaOx-induced kidney damage through the recovery of the antioxidant defense system regulated by miR-128-3p/SIRT1 axis. These findings provide novel insights for the prevention and treatment of renal calculus.

Circular RNAs in prostate cancer: Biogenesis,biological functions, and clinical significance.

Circular RNAs (circRNAs) are covalently closed RNA molecules that play important regulatory roles in various tumors. Prostate cancer (PCa) is one of the most common malignant tumors in the world, with high morbidity and mortality. In recent years, more and more circRNAs have been found to be abnormally expressed and involved in the occurrence and development of PCa, including cell proliferation, apoptosis, invasion, migration, metastasis, chemotherapy resistance, and radiotherapy resistance. Most of the circRNAs regulate biological behaviors of cancer through a competitive endogenous RNA (ceRNA) regulatory mechanism, and some can exert their functions by binding to proteins. circRNAs are also associated with many clinicopathological features of PCa, including tumor grade, lymph node metastasis, and distant metastasis. In addition, circRNAs are potential diagnostic and prognostic biomarkers for PCa. Considering their critical regulatory roles in the progression of PCa, circRNAs would be the potential therapeutic targets. In this paper, the current research status of circRNAs in PCa is briefly reviewed.

Biological Roles and Clinical Significance of Exosome-Derived Noncoding RNAs in Bladder Cancer.

Bladder cancer (BCa) is a common heterogeneous urinary system tumor with high malignancy and limited advancement in treatment. Limited understanding of BCa has not contributed to any significant progress in diagnosis or treatment, exploring the mechanisms underlying BCa has become an urgent research focus. Exosomes, a type of extracellular vesicle (EV), have drawn substantial interest for their important roles in mediating intracellular communication. Exosomes shuttle numerous bioactive molecules, and noncoding RNAs (ncRNAs) are among the most numerous. ncRNAs including microRNA, long noncoding RNA, and circular RNA are sorted and packaged into exosomes selectively and transferred into recipient cells to regulate their function. Exosomal ncRNAs are associated with hallmarks of BCa, such as proliferation, apoptosis, epithelial-mesenchymal transition (EMT), cell cycle arrest, lymphangiogenesis, and chemotherapy resistance. Exosomal ncRNAs can also be detected in urine and serum, making them encouraging biomarkers for BCa diagnosis and prognosis. More importantly, exosomes exhibit excellent biocompatibility and potential for diversified applications. The delivery of bioactive substances and drugs into specific cells has become a promising approach for precision therapy for BCa patients. In addition, cancer vaccines have also received increasing attention. In this review, we summarize the current research on the regulatory roles of exosomal ncRNAs in BCa tumorigenesis and progression, as well as their potential clinical value in accelerating the diagnosis and therapy of BCa.

Rapamycin regulates Akt and ERK phosphorylation through mTORC1 and mTORC2 signaling pathways.

Numerous studies have shown that mammalian target of rapamycin (mTOR) inhibitor activates Akt signaling pathway via a negative feedback loop while inhibiting mTORC1 signaling. In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin-mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors. Moreover, we analyzed the effect of mTORC1 and mTORC2 on regulating cell cycle progression. We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. We further showed that mTORC2 was tightly associated with the development of cell cycle through an Akt-dependent mechanism. Therefore, we combined PI3K and ERK inhibitors prevent rapamycin-induced Akt activation and enhanced antitumor effects of rapamycin. Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin-mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin-based therapeutic approaches in cancer cells.

Predicting Prostate Cancer Upgrading of Biopsy Gleason Grade Group at Radical Prostatectomy Using Machine Learning-Assisted Decision-Support Models.

OBJECTIVE: This study aimed to develop a machine learning (ML)-assisted model capable of accurately predicting the probability of biopsy Gleason grade group upgrading before making treatment decisions. METHODS: We retrospectively collected data from prostate cancer (PCa) patients. Four ML-assisted models were developed from 16 clinical features using logistic regression (LR), logistic regression optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), random forest (RF), and support vector machine (SVM). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Calibration plots and decision curve analysis (DCA) were performed to evaluate the calibration and clinical usefulness of each model. RESULTS: A total of 530 PCa patients were included in this study. The Lasso-LR model showed good discrimination with an AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.776, 0.712, 0.679, 0.745, 0.730, and 0.695, respectively, followed by SVM (AUC=0.740, 95% confidence interval [CI]=0.690-0.790), LR (AUC=0.725, 95% CI=0.674-0.776) and RF (AUC=0.666, 95% CI=0.618-0.714). Validation of the model showed that the Lasso-LR model had the best discriminative power (AUC=0.735, 95% CI=0.656-0.813), followed by SVM (AUC=0.723, 95% CI=0.644-0.802), LR (AUC=0.697, 95% CI=0.615-0.778) and RF (AUC=0.607, 95% CI=0.531-0.684) in the testing dataset. Both the Lasso-LR and SVM models were well-calibrated. DCA plots demonstrated that the predictive models except RF were clinically useful. CONCLUSION: The Lasso-LR model had good discrimination in the prediction of patients at high risk of harboring incorrect Gleason grade group assignment, and the use of this model may be greatly beneficial to urologists in treatment planning, patient selection, and the decision-making process for PCa patients.

Combined multiple clinical characteristics for prediction of discordance in grade and stage in prostate cancer patients undergoing systematic biopsy and radical prostatectomy.

BACKGROUND: The present study aimed to develop three nomograms by incorporating multiple clinical characteristics to identify those prostate cancer (PCa) patients with high probability of incorrect biopsy Gleason grade group (GG) before making treatment decisions. METHODS: We retrospectively collected data from PCa patients who underwent systematic biopsy and radical prostatectomy from January 2015 to December 2019 at Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology. Univariable and multivariable logistic regression analyses were preformed to identify independent risk factors associated with upgrading, upstaging and downgrading. By incorporating selected clinical parameters with high predictive value, we constructed three nomograms to predict the probability of upgrading, upstaging and downgrading. Discrimination of nomograms was evaluated by receiver operating characteristic (ROC) analysis with corresponding area under the curve (AUC). Decision curve analysis (DCA) and calibration curves were performed to evaluate calibration and the clinical usefulness of nomograms. Performance of the three nomograms was validated in the testing dataset. RESULTS: There were 585 PCa patients in total enrolled in this study who met the inclusion criteria. Of the 585 patients, the disease of 262 (44.8 %) was upgraded and 68 (11.6 %) was downgraded, and the disease of 67 (11.5 %) was upstaged. With regard to findings of multivariable analyses, patients' age and biopsy GG (GG 2, GG 3, GG 4 versus GG 1) were significantly associated with upgrading. Moreover, maximum diameter of the index lesion (D-max), clinical T stage (cT3a, cT3b versus cT1-2), number of positive cores and total tumor length were significantly associated with upstaging. Furthermore, d-max, %fPSA (> 0.16 versus ≤ 0.16) and biopsy GG (GG 3, GG 4, GG 5 versus GG 2) were independent predictors of downgrading. The three nomograms displayed good calibration in respective calibration plots. ROC analyses showed good discrimination with satisfactory AUC values and DCA plots demonstrated that the upgrading-risk nomogram, upstaging-risk nomogram and downgrading-risk nomogram were all clinically useful. CONCLUSIONS: The upgrading-risk nomogram, upstaging-risk nomogram, and downgrading-risk nomogram were developed and correctly predicted the probability of incorrect Gleason grade group assigned to patients undergoing systematic biopsy.