Expression profiles of urine exosomal tRNA-derived small RNAs and their potential roles in calcium oxalate stone disease.

Background and objective: Exosomes have been confirmed to be implicated in the pathogenesis of calcium oxalate (CaOx) stones. tRNA-derived small RNAs (tsRNAs) are among the oldest small RNAs involved in exosome-mediated intercellular communication, yet their role in kidney stones remains unexplored. This pilot study aimed to identify differentially expressed tsRNAs (DEtsRNAs) in urine exosomes between CaOx stone patients and healthy controls and explore their potential roles in nephrolithiasis. Method: First-morning urine samples were collected from three CaOx stone patients and three healthy controls. Urinary exosomes were isolated and analyzed by high-throughput sequencing to generate the expression profiles of tsRNAs and detect DEtsRNAs. Predicted target genes of DEtsRNAs were subjected to functional enrichment analysis. The authors also combined the public dataset GSE73680 to investigate how DEtsRNAs were related to stone formation. Results: Four DEtsRNAs were significantly upregulated in CaOx stone patients compared to healthy controls. tRF-Lys-TTT-5005c was the most elevated, followed by tRF-Lys-CTT-5006c, tRF-Ala-AGC-5017b, and tRF-Gly-CCC-5004b. Bioinformatics analysis indicated that these four types of DEtsRNAs might serve distinct biological functions. Combined with data mining from the public dataset GSE73680, the authors assumed that exosomes carrying tRF-Lys-TTT-5005c and tRF-Lys-CTT-5006c could inhibit the expression of SMAD6, FBN1, and FZD1, thereby activating the BMP signaling pathway, which might induce an osteogenic-like transformation in target cells, resulting in the formation of Randall's plaques and CaOx stones. Conclusion: The authors' findings shed light on the potential roles of tsRNAs in the pathogenesis of CaOx stone disease, highlighting exosomal DEtsRNAs as promising diagnostic biomarkers and therapeutic targets in nephrolithiasis.

The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG.

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette-Guérin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment.

Neoadjuvant gemcitabine-cisplatin plus tislelizumab in persons with resectable muscle-invasive bladder cancer: a multicenter, single-arm, phase 2 trial.

Programmed death 1 blockade (tislelizumab) has been approved for metastatic urothelial carcinoma but not as part of neoadjuvant therapy for muscle-invasive bladder cancer (MIBC). In this multicenter single-arm trial (ChiCTR2000037670), 65 participants with cT2-4aN0M0 MIBC received neoadjuvant gemcitabine-cisplatin plus tislelizumab; 57 of them underwent radical cystectomy (RC). The primary endpoint of pathologic complete response (pCR) rate was 50.9% (29/57, 95% confidence interval (CI) 37.3-64.4%) and the pathologic downstaging (secondary endpoint) rate was 75.4% (43/57, 95% CI 62.2-85.9%) in participants undergoing RC. Genomic and transcriptomic analyses revealed three MIBC molecular subtypes (S): S1 (immune-desert) with activated cell-cycle pathway, S2 (immune-excluded) with activated transforming growth factor-ß pathway and S3 (immune-inflamed) with upregulated interferon-α and interferon-γ response. Post hoc analysis showed pCR rates of 16% (3/19, S1), 77% (10/13, S2) and 80% (12/15, S3) (P = 0.006). In conclusion, neoadjuvant gemcitabine-cisplatin plus tislelizumab for MIBC was compatible with an enhanced pCR rate.

Design, synthesis and biological evaluation of dual inhibitors targeting AR/AR-Vs and PARP1 in castration resistant prostate cancer therapy.

The combination of androgen signaling inhibitors and PARP inhibitors has shown promising results in clinical trials for the treatment of castration-resistant prostate cancer (CRPC). Multi-target inhibitors can inhibit tumors through different pathways, addressing the limitations of traditional single target inhibitors. We designed and synthesized dual inhibitors targeting AR/AR-Vs and PARP1 using a pharmacophore hybridization strategy. The most potent compound, II-3, inhibits AR/AR-Vs signaling and induces DNA damage by inhibiting PARP1. The IC50 values of II-3 in the castration-resistant prostate cancer cell lines 22RV1 and C4-2 are 4.38 ± 0.56 µM, and 3.44 ± 0.63 µM, respectively. II-3 not only suppresses the proliferation and migration of 22RV1 and C4-2 cells, but also promotes their apoptosis. Intraperitoneal injection of II-3 effectively inhibits tumor growth in 22RV1 xenograft nude mice without evident drug-induced toxicity. Overall, a series of novel dual inhibitors targeting AR/AR-Vs and PARP1 were designed and synthesized, and meanwhile the in vivo and in vitro effects were comprehensively explored, which provided a potential new therapeutic strategy for CRPC.

A Clinical Evaluation of Robotic-assisted Radical Prostatectomy (RARP) in Located Prostate Cancer: A Systematic Review and Network Meta-analysis.

Prostate cancer (PCa) is a prevalent malignant tumor affecting the male reproductive system and there are mainly three widely accepted PCa surgery types in current clinical treatment: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). Here, we aimed to evaluate the clinical effect of RARP for PCa patients compared with ORP and LRP based on the context of PCa encompass two dimensions: oncological outcomes (biochemical recurrence (BCR) and positive surgical margin (PSM)) and functional outcomes (urinary continence and recovery of erectile function) in this network meta-analysis (NMA). PubMed, Embase and Cochrane databases were systematically searched in January 7, 2024. 4 randomized controlled trials (RCTs) and 72 non-RCTs were included. RARP displayed significant positive effect on lower BCR and better recovery of erectile function but no significant differences existed among three surgery types for PSM and urinary continence.

Trends in focal therapy for localized prostate cancer: a bibliometric analysis from 2014 to 2023.

Focal therapy, a minimally invasive strategy for localized prostate cancer, has been widely employed in the targeted treatment of localized prostate cancer in recent years. We analyzed 1312 relevant papers from the last decade using Web of Science Core Collection data. Our analysis covered countries, institutions, journals, authors, keywords, and references to offer a multifaceted perspective on the development of this field. The U.S. led in publications, contributing over half of the top 10 institutions. Emberton, M from University College London was the most published and cited author. "EUROPEAN UROLOGY" was the top journal by impact factor in 2022. Analysis of references and keywords suggests the prevalence of brachytherapy-related research, while high-intensity focused ultrasound (HIFU), cryotherapy, and irreversible electroporation (IRE) are emerging as new research focuses. Consequently, more high-quality evidence is necessary to evaluate the long-term effectiveness and safety of these novel therapeutic methods.

Partial prostatectomy for localized prostate cancer.

BACKGROUND AND OBJECTIVE: Localized prostate cancer treatment aims to balance cancer control with preserving urinary and erectile function. While focal ablative therapies have emerged, their uncertain prognosis prompts exploration of partial prostatectomy. We systematically reviewed its efficacy as a primary treatment, particularly in low-to-intermediate-risk patients. METHODS: Our review comprehensively analyzed existing studies on partial prostatectomy for localized cancer. We focused on patient selection, surgical techniques, and postoperative outcomes, emphasizing tumor control, continence, and erectile function. Studies involving multiparametric MRI and targeted biopsies for candidate selection were included. KEY FINDINGS AND LIMITATIONS: Partial prostatectomy, encompassing various techniques, demonstrates promising short-term outcomes in tumor control and functional preservation. Preoperative imaging and biopsy aid in candidate selection. However, longer-term data on cancer recurrence are limited, warranting further investigation. Heterogeneity among studies and the lack of standardized follow-up protocols are notable limitations. CONCLUSIONS AND CLINICAL IMPLICATIONS: Partial prostatectomy offers a minimally invasive and effective treatment option for localized prostate cancer, particularly in selected patients. Preoperative imaging and biopsy play crucial roles in patient selection, while standardized follow-up protocols are needed to assess long-term outcomes. Future research should focus on elucidating its precise role and optimizing patient selection criteria, contributing to improved prostate cancer management strategies. ADVANCING PRACTICE: Partial prostatectomy is explored for localized prostate cancer treatment, aiming to balance cancer control with preserving function. Short-term outcomes are promising, but long-term data on recurrence are lacking. Further research is needed to optimize patient selection and standardize follow-up protocols.

Prediction of clear cell renal cell carcinoma prognosis based on an immunogenomic landscape analysis.

Immune cell infiltration and tumor-related immune molecules play key roles in tumorigenesis and tumor progression. The influence of immune interactions on the molecular characteristics and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. A machine learning algorithm was applied to the transcriptome data from The Cancer Genome Atlas database to determine the immunophenotypic and immunological characteristics of ccRCC patients. These algorithms included single-sample gene set enrichment analyses and cell type identification. Using bioinformatics techniques, we examined the prognostic potential and regulatory networks of immune-related genes (IRGs) involved in ccRCC immune interactions. Fifteen IRGs (CCL7, CHGA, CMA1, CRABP2, IFNE, ISG15, NPR3, PDIA2, PGLYRP2, PLA2G2A, SAA1, TEK, TGFA, TNFSF14, and UCN2) were identified as prognostic IRGs associated with overall survival and were used to construct a prognostic model. The area under the receiver operating characteristic curve at 1 year was 0.927; 3 years, 0.822; and 5 years, 0.717, indicating good predictive accuracy. Molecular regulatory networks were found to govern immune interactions in ccRCC. Additionally, we developed a nomogram containing the model and clinical characteristics with high prognostic potential. By systematically examining the sophisticated regulatory mechanisms, molecular characteristics, and prognostic potential of ccRCC immune interactions, we provided an important framework for understanding the molecular mechanisms of ccRCC and identifying new prognostic markers and therapeutic targets for future research.

Comparing the diagnostic value of 68Ga-prostate-specific membrane antigen PET/CT and multiparametric MRI in pelvic lymph node metastasis of locally advanced prostate cancer.

Background: Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in locally advanced PCa (LAPC) patients. Therefore, we designed a retrospective study to compare the diagnostic value of 68Ga-PSMA PET/CT and mpMRI for PLNM of LAPC. Methods: A retrospective study was performed on 50 patients with LAPC who underwent radical prostatectomy (RP) in Tongji Hospital from 2021 to 2023. All patients underwent PET/CT and mpMRI examination, and were diagnosed as LAPC before surgery, followed by robot-assisted laparoscopic prostatectomy or laparoscopic RP and extended pelvic lymph node dissection (ePLND). Routine postoperative pathological examination was performed. According to the results, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT and mpMRI for the diagnosis of PLNM of LAPC were compared. Results: Among the 50 patients, the mean age was 65.5±10.3 years, the preoperative total serum prostate-specific antigen (PSA) was 30.7±12.3 ng/mL, and the Gleason score was 7 [7, 8]. The difference in diagnostic efficacy between 68Ga-PSMA PET/CT and mpMRI in the preoperative diagnosis of PLNM of PCa was determined by postoperative pathological results. Based on the number of patients who developed PLNM, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were as follows: 93.75%, 100.00%, 100.00%, 97.14%, and 68.75%, 97.06%, 91.67%, 86.84% for mpMRI, respectively. Based on the number of pelvic metastatic lymph nodes, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were 95.24%, 100.00%, 100.00%, 99.48%, and 65.08%, 99.13%, 89.13%, 96.30% for mpMRI, respectively. It turned out that PET/CT was more sensitive than mpMRI in detecting PLNM of PCa, and the difference was statistically significant. Conclusions: 68Ga-PSMA PET/CT is more sensitive than mpMRI in the detection of PLNM in patients with LAPC. It is a promising method in the diagnosis and preoperative assessment of PLNM in LAPC.

The application of laparoscopic ultrasound-guided intervention in renal hybrid surgery: case report.

Background: Conventional vascular interventions and hybrid surgery relied on digital subtraction angiography (DSA). Previously our center explored hybrid partial nephrectomy with DSA guidance, which demonstrates the superiority of omitting the dissection of renal hilum. However, this approach is limited to scarce hybrid operating rooms, involves radiation exposure, and poses compatibility issues with robotic surgery platforms. Laparoscopic ultrasound (LUS) can assist in robotic surgery. This study explored the application of LUS-guided occlusion of renal artery blood supply with a Fogarty balloon catheter, particularly in hybrid partial nephrectomy for renal tumor treatment. Case Description: The LUS-guided renal artery balloon catheter occluded hybrid partial nephrectomy (UBo-HPN) involved several steps: trans-femoral artery cannulation, placement of the balloon catheter into the renal artery via the femoral vascular sheath, occlusion of the renal blood supply by inflating the balloon catheter, completion of zero-ischemia partial nephrectomy with arterial flow occluded, withdrawal of the balloon catheter after deflation. For all three patients, the balloon catheter was successfully and accurately placed into the selected renal artery under LUS guidance. Intraoperative occlusion of the renal blood supply was confirmed to be complete and reversible. No complications were observed during follow-up. Conclusions: LUS guidance presents a safe alternative to DSA guidance for assisting in hybrid surgery. LUS-guided hybrid partial nephrectomy is safe and feasible.

68Ga-PSMA PET/CT and 18F-FDG PET/CT in the diagnosis of prostatic ductal cancer.

PURPOSES: To explore the characteristics of PSMA PET/CT and FDG PET/CT images in prostatic ductal adenocarcinoma (DA) patients. METHODS: We retrospectively enrolled prostatic DA patients with PET/CT scans at Tongji Hospital from 2018 to 2022. Patients with prostatic acinar adenocarcinoma (AA) and benign pathology (BP) were enrolled by 1:1 matching. Differences in the uptake of primary and metastatic foci on PET among the groups were analyzed. RESULTS: A total of 42 patients were enrolled: 14 in each group. In primary foci, the mean PSMA uptake in the DA group was lower than that in the AA group (14.2 ± 9.6 vs. 27.1 ± 14.3, P = 0.009) and greater than that in the BP group (14.2 ± 9.6 vs. 4.7 ± 1.3, P = 0.003). The AUCs of the DA-AA ROC curve and DA-BP ROC curve were 0.781 and 0.872, respectively. The median PSMA uptake of metastatic lymph nodes in the DA group was lower than that in the AA group (5.6 vs. 14.2, P = 0.033), with no significant difference in metastatic bone lesions (9.5 vs 19.1, P = 0.485). No significant difference was found in the FDG uptake of primary and metastatic foci between the DA and AA groups (P > 0.05). CONCLUSION: Prostatic DA has greater PSMA uptake than BP diseases, but lower uptake in both primary foci and metastatic lymph nodes than AA on PSMA PET/CT, aiding in the differential diagnosis of DA, AA and BP diseases. Clinicians should combine traditional imaging with PSMA PET/CT to avoid underestimating the clinical stage of DA patients.

[Effect and safety of pulsatile GnRH therapy for male congenital hypogonadotropic hypogonadism].

OBJECTIVE: To investigate the efficiency and safety of the pulsatile GnRH therapy in the treatment of male congenital hypogonadotropic hypogonadism (CHH). METHODS: We retrospectively analyzed the clinical data on 45 CHH males treated by pulsatile GnRH therapy in our hospital from January 2013 to March 2023. We treated the patients with gonadorelin at 7－15 µg, one pulse/90 min, and followed them up every month in the first 3 months and then every 3 to 6 months after treatment, for an average of 19.1±4.3 months, during which we recorded the height, body weight, penile length, testis volume, Tanner stages, levels of FSH, LH and T, semen parameters and adverse reactions of the patients, followed by comparison of the data obtained with the baseline. RESULTS: The levels of FSH, LH and T of the patients were dramatically elevated after treatment (P < 0.01). The T level of the 6 cases of cryptorchidism, however, failed to reach the normal value within 18.2 ± 8.6 months of follow-up. Significant improvement was seen in the external genitalia and secondary sexual characteristics of all the patients, and spermatogenesis was observed in the semen in 33 cases (73.3%), with a mean sperm concentration of (18.2 ± 6.2) 106/ml, sperm progressive motility of (19.7 ± 6.5) %, and semen volume of (1.8 ± 0.6) ml. Eight of the cases achieved natural fertility, and another 3 achieved childbirth by assisted reproductive technology. As for adverse events, gynecomastia was observed in 8, subcutaneous induration in 6, and allergic reaction to therapeutic agent in 3 cases. CONCLUSION: Pulsatile GnRH therapy is an effective and safe strategy for male CHH. However, clinicians should choose appropriate approaches to different individual cases.

Clinical-imaging metrics for the diagnosis of prostate cancer in PI-RADS 3 lesions.

OBJECTIVE: To explore the feasibility and efficacy of clinical-imaging metrics in the diagnosis of prostate cancer (PCa) and clinically significant prostate cancer (csPCa) in prostate imaging-reporting and data system (PI-RADS) category 3 lesions. METHODS: A retrospective analysis was conducted on lesions diagnosed as PI-RADS 3. They were categorized into benign, non-csPCa and csPCa groups. Apparent diffusion coefficient (ADC), T2-weighted imaging signal intensity (T2WISI), coefficient of variation of ADC and T2WISI, prostate-specific antigen density (PSAD), ADC density (ADCD), prostate-specific antigen lesion volume density (PSAVD) and ADC lesion volume density (ADCVD) were measured and calculated. Univariate and multivariate analyses were used to identify risk factors associated with PCa and csPCa. Receiver operating characteristic curve (ROC) and decision curves were utilized to assess the efficacy and net benefit of independent risk factors. RESULTS: Among 202 patients, 133 had benign prostate disease, 25 non-csPCa and 44 csPCa. Age, PSA and lesion location showed no significant differences (P > 0.05) among the groups. T2WISI and coefficient of variation of ADC (ADCcv) were independent risk factors for PCa in PI-RADS 3 lesions, yielding an area under the curve (AUC) of 0.68. ADC was an independent risk factor for csPCa in PI-RADS 3 lesions, yielding an AUC of 0.65. Decision curve analysis showed net benefit for patients at certain probability thresholds. CONCLUSIONS: T2WISI and ADCcv, along with ADC, respectively showed considerable promise in enhancing the diagnosis of PCa and csPCa in PI-RADS 3 lesions.

Identification of Calculous Pyonephrosis by CT-Based Radiomics and Deep Learning.

Urgent detection of calculous pyonephrosis is crucial for surgical planning and preventing severe outcomes. This study aims to evaluate the performance of computed tomography (CT)-based radiomics and a three-dimensional convolutional neural network (3D-CNN) model, integrated with independent clinical factors, to identify patients with calculous pyonephrosis. We recruited 182 patients receiving either percutaneous nephrostomy tube placement or percutaneous nephrolithotomy for calculous hydronephrosis or pyonephrosis. The regions of interest were manually delineated on plain CT images and the CT attenuation value (HU) was measured. Radiomics analysis was performed using least absolute shrinkage and selection operator (LASSO). A 3D-CNN model was also developed. The better-performing machine-learning model was combined with independent clinical factors to build a comprehensive clinical machine-learning model. The performance of these models was assessed using receiver operating characteristic analysis and decision curve analysis. Fever, blood neutrophils, and urine leukocytes were independent risk factors for pyonephrosis. The radiomics model showed higher area under the curve (AUC) than the 3D-CNN model and HU (0.876 vs. 0.599, 0.578; p = 0.003, 0.002) in the testing cohort. The clinical machine-learning model surpassed the clinical model in both the training (0.975 vs. 0.904, p = 0.019) and testing (0.967 vs. 0.889, p = 0.045) cohorts.

PD-L1 expression and its correlation with tumor biomarkers in Chinese urothelial bladder cancer.

Data on prevalence of programmed death ligand-1 (PD-L1) expression and its correlation with tumor biomarkers in Chinese patients with muscle-invasive urothelial bladder cancer (MIUBC) are scarce. We investigated the prevalence of PD-L1 expression, PD-L1 expression in tumor cells (TC) and immune cells (IC), and its correlation with tumor biomarkers (CD8+ T cells and tumor mutation burden [TMB]) in Chinese patients with newly diagnosed MIUBC (NCT03433924). Of 248 patients enrolled, 229 with PD-L1 data available were analysed. High PD-L1 expression (≥ 25% of TC or IC with PD-L1 expression) was observed in 120 (52.4%) patients. 59 cases showed positive staining in ≥ 25% of TC, and 82 cases had positive staining in ≥ 25% of IC. High expression of CD8+ T cell and TMB (> 10 mutations/megabase) was observed in 44.5% and 54.1% patients, respectively. A positive correlation was observed between percentage of TC with membrane PD-L1 positivity and CD8+ T cells (0.34; P < 0.001) and between IC with membrane PD-L1 positivity and CD8+ T cells (0.44; P < 0.001). There is high prevalence of PD-L1 expression in Chinese patients with MIUBC, suggesting that a sizable subset of patients could benefit from immunotherapy. The correlation of PD-L1 expression with tumor biomarkers provide clues for mechanisms underlying the effects of biomarkers for predicting efficacy.

Energy-saving hydrogen production by seawater electrolysis coupling tip-enhanced electric field promoted electrocatalytic sulfion oxidation.

Hydrogen production by seawater electrolysis is significantly hindered by high energy costs and undesirable detrimental chlorine chemistry in seawater. In this work, energy-saving hydrogen production is reported by chlorine-free seawater splitting coupling tip-enhanced electric field promoted electrocatalytic sulfion oxidation reaction. We present a bifunctional needle-like Co3S4 catalyst grown on nickel foam with a unique tip structure that enhances the kinetic rate by improving the current density in the tip region. The assembled hybrid seawater electrolyzer combines thermodynamically favorable sulfion oxidation and cathodic seawater reduction can enable sustainable hydrogen production at a current density of 100 mA cm-2 for up to 504 h. The hybrid seawater electrolyzer has the potential for scale-up industrial implementation of hydrogen production by seawater electrolysis, which is promising to achieve high economic efficiency and environmental remediation.

The association between diabetes mellitus and prostate cancer: a meta-analysis and Mendelian randomization.

BACKGROUND: Prostate cancer is one of the most common types of cancer in the US, and it has a high mortality rate. Diabetes mellitus is also a dangerous health condition. While some studies have examined the relationship between diabetes mellitus and the risk of prostate cancer, there is still some debate on the matter. This study aims to carefully assess the relationship between prostate cancer and diabetes from both real-world and genetic-level data. METHODS: This meta-analysis was conducted following the PRISMA 2020 reporting guidelines. The study searched three databases including Medline, Embase and Cochrane. The studies about the incidence risk of prostate cancer with diabetes mellitus were included and used to evaluate the association. The odds ratio (OR), risk ratio (RR) and 95% confidence intervals (95% CI) were estimated using Random Effects models and Fixed Effects models. Mendelian randomization study using genetic variants was also conducted. RESULTS: A total of 72 articles were included in this study. The results showed that risk of prostate cancer decreased in diabetes patients. And the influence was different in different regions. This study also estimated the impact of body mass index (BMI) in the diabetes populations and found that the risk decreased in higher BMI populations. The MR analysis found that diabetes mellitus exposure reduced the risk of prostate cancer in the European population and Asia populations. Conclusions The diabetes mellitus has a protective effect on prostate cancer. And the influence of obesity in diabetes mellitus plays an important role in this effect.

Chitosan Oligosaccharide Laser Lithograph: A Facile Route to Porous Graphene Electrodes for Flexible On-Chip Microsupercapacitors.

In this study, a convenient chitosan oligosaccharide laser lithograph (COSLL) technology was developed to fabricate laser-induced graphene (LIG) electrodes and flexible on-chip microsupercapacitors (MSCs). With a simple one-step CO2 laser, the pyrolysis of a chitosan oligosaccharide (COS) and in situ welding of the generated LIGs to engineering plastic substrates are achieved simultaneously. The resulting LIG products display a hierarchical porous architecture, excellent electrical conductivity (6.3 Ω sq-1), and superhydrophilic properties, making them ideal electrode materials for MSCs. The pyrolysis-welding coupled mechanism is deeply discussed through cross-sectional analyses and finite element simulations. The MSCs prepared by COSLL exhibit considerable areal capacitance of over 4 mF cm-2, which is comparable to that of the polyimide-LIG-based counterpart. COSLL is also compatible with complementary metal-oxide-semiconductor (CMOS) and micro-electro-mechanical system (MEMS) processes, enabling the fabrication of LIG/Au MSCs with comparable areal capacitance and lower internal resistance. Furthermore, the as-prepared MSCs demonstrate excellent mechanical robustness, long-cycle capability, and ease of series-parallel integration, benefiting their practical application in various scenarios. With the use of eco-friendly biomass carbon source and convenient process flowchart, the COSLL emerges as an attractive method for the fabrication of flexible LIG on-chip MSCs and various other advanced LIG devices.

The prognostic impact of tumor location in nonmuscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing Chinese multicenter and SEER registries.

OBJECTIVE: Most bladder cancers are nonmuscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach. METHODS: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias. RESULTS: This study included 118 477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 ( P <0.0001); RFS of 2.21 ( P <0.0001); SEER cohort OS HR of 1.10 ( P =0.0001); DSS HR of 1.13 ( P =0.0183). Dome tumors displayed similar trends [Chinese NMIBC cohort OS HR of 7.91 ( P <0.0001); RFS HR of 2.12 ( P <0.0001); SEER OS HR of 1.05 ( P =0.0087); DSS HR of 1.14 ( P =0.0006)]. Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment ( P <0.01). CONCLUSION: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients.

A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.