Recent Advances of Neoadjuvant Immunotherapy for Urothelial Bladder Cancer.

Urothelial bladder cancer is one of the most common malignant tumors of the urinary system, which accounts for 90~95% of urothelial carcinoma. Despite the current standard neoadjuvant management for localized urothelial MIBC (T2-4cN0M0) is cisplatin-based chemotherapy before radical cystectomy, there still had poor performances and less overall survival benefits in patients with localized urothelial MIBC. Moreover, nearly half of MIBC patients were ineligible for receiving cisplatin because of chronic kidney disease and performance status. Although immunotherapy, immune checkpoint inhibitors (ICIs) has been identified as first or second-line treatments for localized and metastasis bladder cancer based on less adverse reactions and favorable outcomes, neoadjuvant immunotherapy had rarely used for the treatment of these patients because of less large-scale clinical randomized studies and limited outcomes. Therefore, we reviewed the advances of efficacy and safety with neoadjuvant immunotherapy for urothelial bladder cancer depended on published articles and clinical studies, which could provide more theoretical evidences and promising strategy for clinical therapeutic development.

The application of nanoparticles-based ferroptosis, pyroptosis and autophagy in cancer immunotherapy.

Immune checkpoint blockers (ICBs) have been applied for cancer therapy and achieved great success in the field of cancer immunotherapy. Nevertheless, the broad application of ICBs is limited by the low response rate. To address this issue, increasing studies have found that the induction of immunogenic cell death (ICD) in tumor cells is becoming an emerging therapeutic strategy in cancer treatment, not only straightly killing tumor cells but also enhancing dying cells immunogenicity and activating antitumor immunity. ICD is a generic term representing different cell death modes containing ferroptosis, pyroptosis, autophagy and apoptosis. Traditional chemotherapeutic agents usually inhibit tumor growth based on the apoptotic ICD, but most tumor cells are resistant to the apoptosis. Thus, the induction of non-apoptotic ICD is considered to be a more efficient approach for cancer therapy. In addition, due to the ineffective localization of ICD inducers, various types of nanomaterials have been being developed to achieve targeted delivery of therapeutic agents and improved immunotherapeutic efficiency. In this review, we briefly outline molecular mechanisms of ferroptosis, pyroptosis and autophagy, as well as their reciprocal interactions with antitumor immunity, and then summarize the current progress of ICD-induced nanoparticles based on different strategies and illustrate their applications in the cancer therapy.

PODNL1 promotes cell migration and regulates the epithelial/mesenchymal transition process in bladder cancer.

PODNL1, a member of the small leucine-rich proteoglycans family, has been identified to be closely associated with the prognosis of ovarian cancer and glioma. In this study, we explored the role of PODNL1 in the progression of bladder cancer (BLCA). TCGA data analysis showed that the expression level of PODNL1 in BLCA tissues was significantly higher than that in adjacent tissues. The high expression of PODNL1 was related to T stage, N stage, pathological stage, pathological grade and histological type of BLCA. The results of qPCR further confirmed that the expression of PODNL1 in BLCA cell lines was significantly higher than that in normal bladder epithelial cells (SV-HUC-1). In addition, PODNL1 knockdown decreased the proliferation and migration abilities of BLCA cells, while PODNL1 overexpression promoted the proliferation and migration abilities of BLCA cells. WGCNA and functional enrichment analysis showed that PODNL1 expression was closely related to the epithelial mesenchymal transformation (EMT) pathway of BLCA. Furthermore, GSCA database analysis also showed that high expression of PODNL1 activated the EMT pathway of BLCA. The results of qPCR indicated that PODNL1 gene expression level was negatively correlated with e-cadherin expression, and positively correlated with N-cadherin expression. Thus, these results suggest that PODNL1 regulates EMT process. Additionally, high expression of PODNL1 was closely associated with poor prognosis in BLCA patients. In conclusion, PODNL1 is a potential therapeutic target and prognostic biomarker of BLCA.

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.

Cell membrane coated nanoparticles as a biomimetic drug delivery platform for enhancing cancer immunotherapy.

Cancer immunotherapy, a burgeoning modality for cancer treatment, operates by activating the autoimmune system to impede the growth of malignant cells. Although numerous immunotherapy strategies have been employed in clinical cancer therapy, the resistance of cancer cells to immunotherapeutic medications and other apprehensions impede the attainment of sustained advantages for most patients. Recent advancements in nanotechnology for drug delivery hold promise in augmenting the efficacy of immunotherapy. However, the efficacy is currently constrained by the inadequate specificity of delivery, low rate of response, and the intricate immunosuppressive tumor microenvironment. In this context, the investigation of cell membrane coated nanoparticles (CMNPs) has revealed their ability to perform targeted delivery, immune evasion, controlled release, and immunomodulation. By combining the advantageous features of natural cell membranes and nanoparticles, CMNPs have demonstrated their unique potential in the realm of cancer immunotherapy. This review aims to emphasize recent research progress and elucidate the underlying mechanisms of CMNPs as an innovative drug delivery platform for enhancing cancer immunotherapy. Additionally, it provides a comprehensive overview of the current immunotherapeutic strategies involving different cell membrane types of CMNPs, with the intention of further exploration and optimization.

Comparison of conventional (basketing + dusting) and Moses (pop-dusting) holmium lasers during flexible ureteroscopy in the treatment of renal stones between 2 and 3 cm: a randomized clinical trial.

To investigate the feasibility of conventional (basketing + dusting) and Moses (pop-dusting) holmium lasers during flexible ureteroscopy (FURS) in the treatment of 2-3 cm renal calculi and to compare the efficiency and safety of the two methods, a total of 230 patients with 2-3 cm kidney stones who underwent FURS were randomly divided into the conventional group and the Moses group. The mode of lithotripsy in the conventional group was fragmentation and dusting. The mode of lithotripsy in the Moses group was dusting and pop-dusting. Clinical and perioperative variables and complications were compared between the two cohorts. Multivariate analyses of factors contributing to the stone-free rate (SFR) and operation time were performed. No statistically significant differences were found in the demographics, renal stone-related data, SFR, or complications between the cohorts. The laser energy was higher in the Moses cohort than in the conventional cohort (119.3 ± 15.2 vs. 92.8 ± 15.1 kJ; P < 0.001), and the operation time was shorter in the Moses cohort than in the conventional cohort (99.5 ± 18.9 vs. 105.3 ± 13.7 min; P = 0.009). When there was isolated stone, the operation time was shorter in the Moses cohort than in the conventional cohort (99.6 ± 17.5 vs. 111.4 ± 10.7 min; P < 0.001), while there was no significant difference between the two cohorts when there were multiple stones (99.5 ± 20 vs. 101.2 ± 14 min; P = 0.415). Multivariate analyses found that an increase in stone volume can decrease the SFR and prolong the operation time, and use of a Moses laser can shorten the operation time. Both holmium laser modes during FURS can effectively treat 2-3 cm renal calculi. The Moses mode is recommended as the first choice for the treatment of isolated 2-3 cm renal stones. When treating multiple stones, the efficiency of these two laser modalities is the same. TRIAL REGISTRATION: ChiCTR2200056091.

Nanodelivery Optimization of IDO1 Inhibitors in Tumor Immunotherapy: Challenges and Strategies.

Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.

Recent Advances in Nanomaterials for the Treatment of Acute Kidney Injury.

Acute kidney injury (AKI) is a serious clinical syndrome with high morbidity, elevated mortality, and poor prognosis, commonly considered a "sword of Damocles" for hospitalized patients, especially those in intensive care units. Oxidative stress, inflammation, and apoptosis, caused by the excessive production of reactive oxygen species (ROS), play a key role in AKI progression. Hence, the investigation of effective and safe antioxidants and inflammatory regulators to scavenge overexpressed ROS and regulate excessive inflammation has become a promising therapeutic option. However, the unique physiological structure and complex pathological alterations in the kidneys render traditional therapies ineffective, impeding the residence and efficacy of most antioxidant and anti-inflammatory small molecule drugs within the renal milieu. Recently, nanotherapeutic interventions have emerged as a promising and prospective strategy for AKI, overcoming traditional treatment dilemmas through alterations in size, shape, charge, and surface modifications. This Review succinctly summarizes the latest advancements in nanotherapeutic approaches for AKI, encompassing nanozymes, ROS scavenger nanomaterials, MSC-EVs, and nanomaterials loaded with antioxidants and inflammatory regulator. Following this, strategies aimed at enhancing biocompatibility and kidney targeting are introduced. Furthermore, a brief discussion on the current challenges and future prospects in this research field is presented, providing a comprehensive overview of the evolving landscape of nanotherapeutic interventions for AKI.

CircRPPH1 accelerates the proliferation and migration of bladder cancer via enhancing the STAT3 signaling pathway.

Bladder cancer (BCa) is a common malignant disease with high recurrence and variable prognosis. Circular RNAs (circRNAs) are implicated in the development of multiple diseases. However, the biological activities of circRNAs in BCa remain largely elusive. In the present study, it was found that circRPPH1 was upregulated in BCa cell lines compared with normal urothelial cells. CircRPPH1 downregulation could inhibit the proliferation, migration and invasion of BCa cells in vitro and in vivo. Mechanistically, it was demonstrated that circRPPH1 can act as a sponge of miR­296­5P to upregulate STAT3, and interact with FUS to promote phosphorylated (p)­STAT3 nuclear transport. Overall, circRPPH1 could promote BCa progression through sponging miR­296­5p to upregulate the expression of STAT3 and interacting with FUS to promote p­STAT3 nuclear transport. CircRPPH1 was first identified to play a tumorigenic role in BCa, which could be an underlying therapeutic target.

Antioxidant nanozymes in kidney injury: mechanism and application.

Excessive production of reactive oxygen species (ROS) in the kidneys is involved in the pathogenesis of kidney diseases, such as acute kidney injury (AKI) and diabetic kidney disease (DKD), and is the main reason for the progression of kidney injury. ROS can easily lead to lipid peroxidation and damage the tubular epithelial cell membrane, proteins and DNA, and other molecules, which can trigger cellular oxidative stress. Effective scavenging of ROS can delay or halt the progression of kidney injury by reducing inflammation and oxidative stress. With the development of nanotechnology and an improved understanding of nanomaterials, more researchers are applying nanomaterials with antioxidant activity to treat kidney injury. This article reviews the detailed mechanism between ROS and kidney injury, as well as the applications of nanozymes with antioxidant effects based on different materials for various kidney injuries. To better guide the applications of antioxidant nanozymes in kidney injury and other inflammatory diseases, at the end of this review we also summarize the aspects of nanozymes that need to be improved. An in-depth understanding of the role played by ROS in the occurrence and progression of kidney injury and the mechanism by which antioxidant nanozymes reduce oxidative stress is conducive to improving the therapeutic effect in kidney injury and inflammation-related diseases.

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.

Comparison of the oncological, perioperative and functional outcomes of partial nephrectomy versus radical nephrectomy for clinical T1b renal cell carcinoma: A systematic review and meta-analysis of retrospective studies.

OBJECTIVE: To conduct a meta-analysis assessing the perioperative, functional and oncological outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) for T1b tumours. The primary endpoints were the oncological outcomes. The secondary endpoints were the perioperative and functional outcomes. METHODS: A systematic literature review was performed by searching multiple databases through February 2019 to identify eligible comparative studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Identified reports were assessed according to the Newcastle-Ottawa Scale for nonrandomized controlled trials. RESULTS: Overall, 13 retrospective cohort studies were included in the analysis. Patients undergoing PN were younger (weighted mean difference [WMD] -3.49 years, 95% confidence interval [CI] -5.16 to -1.82; p<0.0001) and had smaller masses (WMD -0.45 cm, 95% CI -0.59 to -0.31; p<0.0001). There were no differences in the oncological outcome, which was demonstrated by progression-free survival (hazard ratio [HR] 0.70; p=0.22), cancer-specific mortality (HR 0.91; p=0.57) and all-cause mortality (HR 1.01; p=0.96). The two procedures were similar in estimated blood loss (WMD -16.47 mL; p=0.53) and postoperative complications (risk ratio [RR] 1.32; p=0.10), and PN provided better renal function preservation and was related to a lower likelihood of chronic kidney disease onset (RR 0.38; p=0.006). CONCLUSION: PN is an effective treatment for T1b tumours because it offers similar surgical morbidity, equivalent cancer control, and better renal preservation compared to RN.

The presence of intraductal carcinoma of the prostate is closely associated with poor prognosis: a systematic review and meta-analysis.

We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate (IDC-P) for prognosis and the associations between IDC-P and clinicopathological parameters. Studies were identified in PubMed, Cochrane Library, EMBASE, Web of Science, and SCOPUS up to December 1, 2019. Hazard ratios (HRs) for survival data and odds ratios for clinicopathological data with 95% confidence intervals (CIs) were extracted. Heterogeneity was evaluated by the I[2] value, and quality was assessed by the Newcastle-Ottawa Scale criteria. A total of 4179 patients from 13 studies were included. The results showed that IDC-P presence was significantly associated with poor progression-free survival (PFS; HR = 2.31; 95% CI: 1.96-2.73), cancer-specific survival (HR = 1.89; 95% CI: 1.28-2.77), and overall survival (HR = 2.14; 95% CI: 1.53-3.01). In the subgroup analysis, IDC-P presence was significantly associated with poor PFS in prostate cancer treated by radical prostatectomy (HR = 2.48; 95% CI: 2.05-3.00) and treated by radiotherapy (HR = 2.83; 95% CI: 1.65-4.85). Regarding clinicopathological characteristics, patients with IDC-P presence had significantly higher tumor clinical stages, Gleason scores, probabilities of lymph node invasion, positive surgical margins, and positive extraprostatic extension. Our meta-analysis indicates that the presence of IDC-P is closely associated with poor prognosis and adverse clinicopathological characteristics. Our data support the value and clinical utility of the routine detection of IDC-P by pathological examination. These conclusions need further validation, and prospective studies are needed to find better treatment modalities other than traditional first-line therapy for patients with IDC-P.