Evaluation of a novel circulation system for ureteroscopic laser lithotripsy in vitro.

PURPOSE: To evaluate the cooling effect and other advantages of a novel circulation system for ureteroscopic holmium laser lithotripsy (URSL) in a standardized in vitro model. MATERIALS AND METHODS: The novel circulation system was assembled by connecting a 4Fr ureteral catheter and a filter. Trails were divided into a new URSL group and a conventional URSL group. First, different power settings (18-30 W) of the holmium laser and irrigation flow rates (20-50 mL/min) were used to evaluate the thermal effect on the lithotripsy site of all groups. Then, renal pelvic temperature and pressure were assessed during URSL at a power of 1.5 J/20 Hz and irrigation flow rates of (20-50 mL/min). Finally, the whole process of lithotripsy was performed at 1.5 J/20 Hz (operator duty cycle ODC: 50%) with an irrigation flow rate of 30 mL/min. The time required for lithotripsy, visual field clarity, and stone migration were observed. RESULTS: Temperature of the lithotripsy point was significantly lower in the new URSL group than in the conventional group (P < 0.05) with irrigation rates (20, 30 mL/min). The renal pelvic pressure of the new group was significantly lower than that of the conventional group in which intrarenal hypertension developed at an irrigation rate of 50 ml/min. The new group had better visual clarity and lesser stone upward migration when lithotripsy was performed at 1.5 J/20 Hz and 30 ml/min. CONCLUSION: The novel circulation system is more effective in reducing the thermal effects of URSL, pelvic pressure, stone upward migration, and improving the visual clarity of the operative field.

Ferroptosis and its emerging role in kidney stone formation.

Kidney stone is a common and highly recurrent disease in urology, and its pathogenesis is associated with various factors. However, its precise pathogenesis is still unknown. Ferroptosis describes a form of regulated cell death that is driven by unrestricted lipid peroxidation, which does not require the activation of caspase and can be suppressed by iron chelators, lipophilic antioxidants, inhibitors of lipid peroxidation, and depletion of polyunsaturated fatty acids. Recent studies have shown that ferroptosis plays a crucial role in kidney stone formation. An increasing number of studies have shown that calcium oxalate, urate, phosphate, and selenium deficiency induce ferroptosis and promote kidney stone formation through mechanisms such as oxidative stress, endoplasmic reticulum stress, and autophagy. We also offered a new direction for the downstream mechanism of ferroptosis in kidney stone formation based on the "death wave" phenomenon. We reviewed the emerging role of ferroptosis in kidney stone formation and provided new ideas for the future treatment and prevention of kidney stones.

The role of microbiome: a novel insight into urolithiasis.

Urolithiasis, referred to as the formation of stones in the urinary tract, is a common disease with growing prevalence and high recurrence rate worldwide. Although researchers have endeavoured to explore the mechanism of urinary stone formation for novel effective therapeutic and preventative measures, the exact aetiology and pathogenesis remain unclear. Propelled by sequencing technologies and culturomics, great advances have been made in understanding the pivotal contribution of the human microbiome to urolithiasis. Indeed, there are diverse and abundant microbes interacting with the host in the urinary tract, overturning the dogma that urinary system, and urine are sterile. The urinary microbiome of stone formers was clearly distinct from healthy individuals. Besides, dysbiosis of the intestinal microbiome appears to be involved in stone formation through the gut-kidney axis. Thus, the human microbiome has potential significant implications for the aetiology of urolithiasis, providing a novel insight into diagnostic, therapeutic, and prognostic strategies. Herein, we review and summarize the landmark microbiome studies in urolithiasis and identify therapeutic implications, challenges, and future perspectives in this rapidly evolving field. To conclude, a new front has opened with the evidence for a microbial role in stone formation, offering potential applications in the prevention, and treatment of urolithiasis.

CXC Chemokine Receptors in the Tumor Microenvironment and an Update of Antagonist Development.

Chemokine receptors, a diverse group within the seven-transmembrane G protein-coupled receptor superfamily, are frequently overexpressed in malignant tumors. Ligand binding activates multiple downstream signal transduction cascades that drive tumor growth and metastasis, resulting in poor clinical outcome. These receptors are thus considered promising targets for anti-tumor therapy. This article reviews recent studies on the expression and function of CXC chemokine receptors in various tumor microenvironments and recent developments in cancer therapy using CXC chemokine receptor antagonists.

The renal pelvis urobiome in the unilateral kidney stone patients revealed by 2bRAD-M.

BACKGROUND: The pathogenesis of kidney stone disease (KSD) is not fully understood, and potential contributing factors remain to be explored. Several studies have revealed that the urinary microbiome (urobiome) of stone formers was distinct from that of healthy individuals using 16S rRNA gene sequencing, most of which only provided microbial identification at the genus level. 2bRAD sequencing for Microbiome (2bRAD-M) is a novel sequencing technique that enables accurate characterization of the low-biomass microbiome at the species resolution. We aimed to apply 2bRAD-M to profile the renal pelvis urobiome of unilateral kidney stone patients and compared the urobiome with and without stone(s). METHOD: A total of 30 patients with unilateral stones were recruited, and their renal pelvis urine from both sides was collected. A ureteroscope was inserted into the renal pelvis with stone(s) and a ureteral catheter was placed into the ureteroscope to collect renal pelvis urine. This procedure was repeated again with new devices to collect the urine of the other side. 2bRAD-M was performed to characterize the renal pelvis urobiome of unilateral stone formers to explore whether microbial differences existed between the stone side and the non-stone side. RESULTS: The microbial community composition of the stone side was similar to that of the non-stone side. Paired comparison showed that Corynebacterium was increased and Prevotella and Lactobacillus were decreased in the stone side. Four species (Prevotella bivia, Lactobacillus iners, Corynebacterium aurimucosum, and Pseudomonas sp_286) were overrepresented in the non-stone side. 24 differential taxa were also identified between two groups by linear discriminant analysis effect size (LEfSe). Extensive and close connections among genera and species were observed in the correlation analysis. Moreover, a random forest classifier was constructed using specific enriched species, which can distinguish the stone side from the non-stone side with an accuracy of 71.2%. CONCLUSION: This first 2bRAD-M microbiome survey gave an important hint towards the potential role of urinary dysbiosis in KSD and provided a better understanding of mechanism of stone formation.

Transcatheter Angiographic Embolization of Percutaneous Nephrolithotomy-Related Bleeding: A Single-Center Experience.

Background: To evaluate the clinical characteristics and angiographic features of transcatheter angiographic embolization (TAE) in patients with active bleeding after percutaneous nephrolithotomy (PCNL). Methods: Between 2009 and 2018, 45 patients who underwent TAE for hemorrhage control after PCNL were reviewed retrospectively. Patient clinical characteristics and angiographic features of TAE were analyzed. Results: Of the 3148 patients, 45 (1.4%) patients were treated with TAE after PCNL. The interval from the bleeding episode to TAE was 3 days (1,6). Arterial laceration, arteriovenous fistula, and negative angiographic finding were found in 28 (62.2%), 7 (15.6%), and 10 patients (22.2%). Thirty-five patients (92.1%) achieved primary clinical success. The median-corrected hemoglobin decrease from bleeding episode to TAE was 52 g/L (25.25, 71.00). The median-corrected hemoglobin decrease rate from bleeding episode to TAE was 13.11 g/L·d (5.60, 26.12). The hemoglobin decrease from bleeding episode to TAE was lesser in negative angiographic patients (28.50 (10.75,51.25) g/L VS 53.7 (35.0,73.13) g/L) than in positive angiographic patients (P < 0.05). Conclusions: TAE is a safe and effective treatment for post-PCNL bleeding patients. Previous kidney surgery is associated with a higher risk of TAE. Patients with bleeding from multiple negative angiographic findings can be considered for prophylactic embolization.

Work engagement and associated factors among dental nurses in China.

BACKGROUND: Work engagement is affected by many factors. The level of work engagement among dental nurses is unknown. METHODS: A cross-sectional questionnaire survey was conducted among 215 dental nurses. The Utrecht Work Engagement Scale, Chinese Nurse Stressors Scale, Work-related Acceptance and Action Questionnaire, Multi-dimensional Scale of Perceived Social Support, and General Well-Being Schedule were applied to measure Chinese nurses' work engagement, job stress, psychological flexibility, perceived social support and subjective well-being, respectively. Univariate analysis was used to identify the relationships of work engagement with demographic and psychological characteristics. Hierarchical linear regression analysis was applied to test the variance in work engagement accounted for by factors related to work engagement in the univariate analysis. RESULTS: The level of work engagement among Chinese dental nurses was moderate or above. Work engagement was positively associated with perceived social support, psychological flexibility and subjective well-being but negatively correlated with job stress. The hierarchical regression analysis showed that age, job stress, psychological flexibility and subjective well-being were significantly correlated with work engagement, though perceived social support was not, all of those psychological variables together explained 34.7% of the variance in work engagement. CONCLUSIONS: Dental nurses in China had an acceptable level of work engagement in terms of vigour, dedication and absorption. Increased job stress resulted in lower work engagement. Nurses who had higher levels of perceived social support, psychological flexibility and subjective well-being also had higher work engagement. It is necessary to understand the job stress of nurses, strengthen nurses' social support, relieve nurses' job stress, improve nurses' psychological flexibility and subjective well-being, which will improve nurses' work engagement levels.

Advances and challenges in the treatment of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL), a rare variant of non-Hodgkin's lymphoma, is characterized by distinct biological characteristics and clinical behaviors, and patient prognosis is not satisfactory. The advent of high-dose (HD) methotrexate (HD-MTX) therapy has significantly improved PCNSL prognosis. Currently, HD-MTX-based chemotherapy regimens are recognized as first-line treatment. PCNSL is sensitive to radiotherapy, and whole-brain radiotherapy (WBRT) can consolidate response to chemotherapy; however, WBRT-associated delayed neurotoxicity leads to neurocognitive impairment, especially in elderly patients. Other effective approaches include rituximab, temozolomide, and autologous stem-cell transplantation (ASCT). In addition, new drugs against PCNSL such as those targeting the B-cell receptor signaling pathway, are undergoing clinical trials. However, optimal therapeutic approaches in PCNSL remain undefined. This review provides an overview of advances in surgical approaches, induction chemotherapy, radiotherapy, ASCT, salvage treatments, and novel therapeutic approaches in immunocompetent patients with PCNSL in the past 5 years. Additionally, therapeutic progress in elderly patients and in those with relapsed/refractory PCNSL is also summarized based on the outcomes of recent clinical studies.

Impact of Endourological procedures with or without double-J stent on sexual function: a systematic review and meta-analysis.

BACKGROUND: Endourological procedures are widely used to treat benign urinary disorders and the double-J stent is routinely used. However, its potential impact on sexual function remains unclear. Therefore, we performed a quantitative systematic review to determine the relationship between endourological procedures with or without double-J stent and post-operative sexual function. METHODS: We conducted a search of PubMed, EMBASE, Web of Science, and Cochrane Library databases up to December 2018 for studies that compared sexual function before and after endourological procedures. The quality of the included studies was evaluated using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I). We performed subgroup analyses to explore heterogeneity. A random effects model was used to combine the results. RESULTS: Five prospective studies involving 485 sexually active participants were identified. Pooled results showed that, in patients without a double-J stent, the change in sexual function after endourological procedures was not significant in men (mean difference [MD]: - 0.61, 95% confidence interval [CI]: - 1.43 to 0.22, p = 0.148) or women (MD: 0.53, 95% CI: - 0.52 to 1.57, p = 0.322). However, in patients with indwelling double-J stent, sexual function scores significantly declined after the procedure in both men (MD: -4.25, 95% CI: - 6.20 to - 2.30, p < 0.001) and women (MD: -7.17, 95% CI: - 7.88 to - 6.47, p < 0.001). CONCLUSIONS: Our meta-analysis suggests that indwelling double-J stent after endourological procedures could be a crucial factor causing temporary sexual dysfunction post-operatively. Our results may be used to provide evidence-based advice to patients.

Three-dimensional MRI sequences in MS diagnosis and research.

The most recent guidelines for magnetic resonance imaging (MRI) in multiple sclerosis (MS) recommend three-dimensional (3D) MRI sequences over their two-dimensional (2D) counterparts. This development has been made possible by advances in MRI scanner hardware and software. In this article, we review the 3D versions of conventional sequences, including T1-weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR), as well as more advanced scans, including double inversion recovery (DIR), FLAIR2, FLAIR*, phase-sensitive inversion recovery, and susceptibility weighted imaging (SWI).

Soluble CXCL16 promotes TNF-α-induced apoptosis in DLBCL via the AMAD10-NF-κB regulatory feedback loop.

We had previously identified that the co-expression of transmembrane CXCL16 (TM-CXCL16) and its receptor CXCR6 is an independent risk factor for poor survival in patients with diffuse large B-cell lymphoma (DLBCL). However, the impact of the soluble form of CXCL16 (sCXCL16) on the pathogenesis of DLBCL remains unknown. In the present study, the synergistic effect of sCXCL16 and tumor necrosis factor α (TNF-α) on apoptosis in DLBCL cell lines (OCI-LY8 and OCI-LY10) was investigated in vitro. sCXCL16 reinforced TNF-α-mediated inhibition of DLBCL cell proliferation, as determined by the cell counting kit-8 assay. The results of annexin V staining showed that sCXCL16 enhanced TNF-α-induced apoptosis in OCI-LY8 and OCI-LY10 cells through a death receptor-caspase signaling pathway. The results of gene microarray suggested a significant upregulation of differentially expressed genes in the TNF signaling pathway. sCXCL16 increased the concentration of extracellular TNF-α by binding to CXCR6 to activate the nuclear factor-κB (NF-κB) signaling pathway. TNF-α also induced the secretion of sCXCL16 by increasing the expression of ADAM10, which is known to cleave TM-CXCL16 to yield sCXCL16. Moreover, bioinformatics analysis revealed that elevated TNF-α and ADAM10 expression levels in tumor tissues predicted better survival in patients with DLBCL. Thus, our study suggests that sCXCL16 enhances TNF-α-induced apoptosis of DLBCL cells, which may involve a positive feedback loop consisting of TNF-α, ADAM10, sCXCL16, and members of the NF-κB pathway. sCXCL16 and TNF-α may be used as prognostic markers in the clinic, and their combinational use is a promising approach in the context of DLBCL therapy.

GnRH antagonist versus follicular-phase single-dose GnRH agonist protocol in patients of normal ovarian responses during controlled ovarian stimulation.

OBJECTIVE: This study aims to explore the differences of the ovarian stimulation (OS) characteristics, laboratory, and clinical outcomes between follicular-phase single-dose gonadotropin-releasing hormone (GnRH) agonist protocol and GnRH antagonist protocol during controlled ovarian hyperstimulation (COH). METHODS: About 1883 consecutive IVF/ICSI fresh cycles of normal ovarian responders were retrospectively analyzed, with 1229 in the single-dose GnRH agonist protocol group and 654 in the GnRH antagonist protocol group at Reproductive Medical Center of Tongji Hospital from 1 January 2014 to 31 December 2017. RESULTS: The follicular-phase single-dose GnRH agonist group showed significantly more oocytes obtained, higher implantation rate and pregnancy rate, as well as lower luteinizing hormone (LH) level and estradiol (E2)/oocyte ratio on the day of human chorionic gonadotropin (hCG) administration. However, differences were not significant in meiosis II (MII) oocyte rate, two pronuclear zygote (2PN) embryo rate, viable embryo rate or high-quality embryo rate, compared with the GnRH antagonist group. Further comparison of clinical outcomes in the first frozen-thawed cycles did not show significant difference in either implantation or clinical pregnancy rate between the two protocol groups. CONCLUSIONS: Follicular-phase single-dose GnRH agonist protocol may achieve better clinical outcomes in normal ovarian responders, which could be explained more by positive effect on endometrial receptivity rather than embryo quality.

MiRNA-99a can regulate proliferation and apoptosis of human granulosa cells via targeting IGF-1R in polycystic ovary syndrome.

PURPOSE: We aimed to evaluate the regulation of miR-99a to the biological functions of granulosa cells in polycystic ovary syndrome (PCOS) via targeting IGF-1R. METHODS: We collected aspirated follicular fluid in both patients with and without PCOS. Granulosa cells (GCs) were isolated through Percoll differential centrifugation to detect both miR-99a and IGF-1R expressions. We further transfected COV434 cells with miR-99a mimics to establish a miRNA-99a (miR-99a) overexpression model. We explored the regulation of miR-99a to the proliferation and apoptosis of human GCs via IGF-1R in COV434. The effect of different insulin concentrations on miR-99a expression was also evaluated. RESULTS: MiR-99a was significantly downregulated while IGF-1R was upregulated in patients with PCOS. MiR-99a can regulate IGF-1R on a post-transcriptional level. After transfection of miR-99a mimics, the proliferation rate was decreased and apoptosis rate was increased significantly in COV434. Exogenous insulin-like growth factor 1 (IGF-1) treatment could reverse the effect of miR-99a. MiR-99a was negatively and dose-dependently regulated by insulin in vitro. CONCLUSIONS: MiR-99a expression was downregulated in patients with PCOS, the degree of which may be closely related to insulin resistance and hyperinsulinemia. MiR-99a could attenuate proliferation and promote apoptosis of human GCs through targeting IGF-1R, which could partly explain the abnormal folliculogenesis in PCOS.

Exercise training modalities in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis.

INTRODUCTION: Current international guidelines recommend aerobic, resistance, and combined exercises for the management of type 2 diabetes mellitus (T2DM). In our study, we conducted a network meta-analysis to assess the comparative impact of different exercise training modalities on glycemic control, cardiovascular risk factors, and weight loss in patients with T2DM. METHODS: We searched five electronic databases to identify randomized controlled trials (RCTs) that compared the differences between different exercise training modalities for patients with T2DM. The risk of bias in the included RCTs was evaluated according to the Cochrane tool. Network meta-analysis was performed to calculate mean difference the ratio of the mean and absolute risk differences. Data were analyzed using R-3.4.0. RESULTS: A total of 37 studies with 2208 patients with T2DM were included in our study. Both supervised aerobic and supervised resistance exercises showed a significant reduction in HbA1c compared to no exercise (0.30% lower, 0.30% lower, respectively), however, there was a less reduction when compared to combined exercise (0.17% higher, 0.23% higher). Supervised aerobic also presented more significant improvement than no exercise in fasting plasma glucose (9.38 mg/dl lower), total cholesterol (20.24 mg/dl lower), triacylglycerol (19.34 mg/dl lower), and low-density lipoprotein cholesterol (11.88 mg/dl lower). Supervised resistance showed more benefit than no exercise in improving systolic blood pressure (3.90 mmHg lower]) and total cholesterol (22.08 mg/dl lower]. In addition, supervised aerobic exercise was more powerful in improving HbA1c and weight loss than unsupervised aerobic (HbA1c: 0.60% lower; weight loss: 5.02 kg lower) and unsupervised resistance (HbA1c: 0.53% lower) exercises. CONCLUSION: Compared with either supervised aerobic or supervised resistance exercise alone, combined exercise showed more pronounced improvement in HbA1c levels; however, there was a less marked improvement in some cardiovascular risk factors. In terms of weight loss, there were no significant differences among the combined, supervised aerobic, and supervised resistance exercises. TRIAL REGISTRATION: Our study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number: CRD42017067518 .

Tubeless versus standard percutaneous nephrolithotomy: an update meta-analysis.

BACKGROUND: To update a previously published systematic review and meta-analysis on the efficacy and safety of tubeless percutaneous nephrolithotomy (PCNL). METHODS: A systematic literature search of EMBASE, PubMed, Web of Science, and the Cochrane Library was performed to confirm relevant studies. The scientific literature was screened in accordance with the predetermined inclusion and exclusion criteria. After quality assessment and data extraction from the eligible studies, a meta-analysis was conducted using Stata SE 12.0. RESULTS: Fourteen randomized controlled trials (RCTs) involving 1148 patients were included. Combined results demonstrated that tubeless PCNL was significantly associated with shorter operative time (weighted mean difference [WMD], -3.79 min; 95% confidence interval [CI], -6.73 to -0.85; P = 0.012; I2 = 53.8%), shorter hospital stay (WMD, -1.27 days; 95% CI, -1.65 to -0.90; P < 0.001; I2 = 98.7%), faster time to return to normal activity (WMD, -4.24 days; 95% CI, -5.76 to -2.71; P < 0.001; I2 = 97.5%), lower postoperative pain scores (WMD, -16.55 mm; 95% CI, -21.60 to -11.50; P < 0.001; I2 = 95.7%), less postoperative analgesia requirements (standard mean difference, -1.09 mg; 95% CI, -1.35 to -0.84; P < 0.001; I2 = 46.8%), and lower urine leakage (Relative risk [RR], 0.30; 95% CI 0.15 to 0.59; P = 0.001; I2 = 41.2%). There were no significant differences in postoperative hemoglobin reduction (WMD, -0.02 g/dL; 95% CI, -0.04 to 0.01; P = 0.172; I2 = 41.5%), stone-free rate (RR, 1.01; 95% CI, 0.97 to 1.05; P = 0.776; I2 = 0.0%), postoperative fever rate (RR, 1.05; 95% CI, 0.57 to 1.93; P = 0.867; I2 = 0.0%), or blood transfusion rate (RR, 0.79; 95% CI, 0.36 to 1.70; P = 0.538; I2 = 0.0%). The results of subgroup analysis were consistent with the overall findings. The sensitivity analysis indicated that most results remained constant when total tubeless or partial tubeless or mini-PCNL studies were excluded respectively. CONCLUSIONS: Tubeless PCNL is an available and safe option in carefully evaluated and selected patients. It is significantly associated with the advantages of shorter hospital stay, shorter time to return to normal activity, lower postoperative pain scores, less analgesia requirement, and reduced urine leakage.

[Clinical implication of urinary protein markers in diabetic nephropathy and interventional effects of Chinese herbal medicine].

In clinic, some urinary protein makers can dynamically and noninvasively reflect the degree of renal tubular injury in patients with diabetic nephropathy (DN). These urinary biomarkers of tubular damage are broadly divided into two categories. One is newfound, including kidney injury molecule-1 (Kim-1), neutrophil getatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP) and cystatin C (CysC); the other one is classical, including beta2 microglobulin (beta2-MG), retinal binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG). It is reported that, the increases in urinary protein markers are not only closely related to the damage of tubular epithelial cells in DN patients, but also can be ameliorated by the treatment with Chinese herbal compound preparations or Chinese herbal medicine. Recently, although urinary proteomics are used in the protein separation and identification, the traditional associated detection of urinary protein markers is more practical in clinic. At present, it is possible that the associated detection of urinary biomarkers of glomerular and tubular damages may be a feasible measure to reveal the clinical significance of urinary protein markers in DN patients and the interventional effects of Chinese herbal medicine.

Engineered microorganisms: A new direction in kidney stone prevention and treatment.

Numerous studies have shown that intestinal and urinary tract flora are closely related to the formation of kidney stones. The removal of probiotics represented by lactic acid bacteria and the colonization of pathogenic bacteria can directly or indirectly promote the occurrence of kidney stones. However, currently existing natural probiotics have limitations. Synthetic biology is an emerging discipline in which cells or living organisms are genetically designed and modified to have biological functions that meet human needs, or even create new biological systems, and has now become a research hotspot in various fields. Using synthetic biology approaches of microbial engineering and biological redesign to enable probiotic bacteria to acquire new phenotypes or heterologous protein expression capabilities is an important part of synthetic biology research. Synthetic biology modification of microorganisms in the gut and urinary tract can effectively inhibit the development of kidney stones by a range of means, including direct degradation of metabolites that promote stone production or indirect regulation of flora homeostasis. This article reviews the research status of engineered microorganisms in the prevention and treatment of kidney stones, to provide a new and effective idea for the prevention and treatment of kidney stones.

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.

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

OBJECTIVE: Most bladder cancers are non-muscle 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.