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Abstract 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.

Abstract 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

Abstract The perplexing issues related to positive surgical margins and the considerable negative consequences associated with systemic chemotherapy have posed ongoing challenges for clinicians, especially when it comes to addressing bladder cancer treatment. The current investigation describes the production of nanocomposites loaded with gemcitabine (GEM) and cisplatin (CDDP) through the utilization of electrospinning technology. In vitro and in vivo studies have provided evidence of the strong effectiveness in suppressing tumor advancement while simultaneously reducing the accumulation of chemotherapy drugs within liver and kidney tissues. Mechanically, the GEM and CDDP-loaded electrospun nanocomposites could effectively eliminate myeloid-derived suppressor cells (MDSCs) in tumor tissues, and recruit CD8+ T cells and NKp46+ NK cells to kill tumor cells, which can also effectively inhibit tumor microvascular formation. Our investigation into the impact of localized administration of chemotherapy through GEM and CDDP-loaded electrospun nanocomposites on the tumor microenvironment will offer novel insights for tackling tumors. Graphical abstract Drug-loaded electrospun nanofibrous mats suppress bladder tumor growth by improving the tumor immune microenvironment.

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.

Repeat partial nephrectomy (PN) is an effective treatment in improving the prognosis for patients with recurrent renal cancer after initial PN. However, salvage PN (sPN) is inevitably associated with a higher rate of complications, largely because of intraperitoneal adhesions and fibrosis. Here we describe three initial cases for which recurrent renal tumors were treated with a novel minimally invasive approach, namely Ultrasound-guided Renal Artery Balloon catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN).With laparoscopic ultrasound (LUS) guiding a Fogarty catheter to occlude the arterial blood supply, dissection of the renal hilum and most of the abdominal cavity can be avoided. UBo-HPN was successfully performed in three patients. One case of postoperative fever (Clavien-Dindo grade II) occurred, with no other complications. The mean operative time was 106 min, with a mean warm ischemia time of 21 min. UBo-HPN may be considered a safe and effective alternative for sPN, with a minimally invasive surgical footprint and better surgical outcomes.

Objective: This study was designed to evaluate the feasibility, efficacy, and safety of percutaneous ureteroscopy laser unroofing as an ambulatory surgery for symptomatic simple renal cysts under multilevel paravertebral nerve block anesthesia. Methods: From December 2015 to September 2017, 33 simple renal cyst patients who had surgical indications were enrolled. Under ultrasound guidance, the T10/T11, T11/T12, and T12/L1 paravertebral spaces were identified, and 7–10 mL 0.5% ropivacaine was injected at each segment. Then a puncture needle was placed inside the cyst cavity under ultrasonic monitoring. A guidewire was introduced followed by sequential dilation up to 28/30 Fr. The extra parenchymal portion of the cyst wall was dissociated and incised using a thulium laser, and a pathological examination was performed. Results: Sensory loss to pinprick from T8 to L1 and sensory loss to ice from T6 to L2 were observed in all patients. None of the patients complained of pain during surgery. No serious complications occurred perioperatively. After the surgery, all patients recovered their lower limb muscle strength quickly, got out of bed, resumed oral feeding, and left the hospital within 24 h of admission. The pathologic diagnosis of all cyst walls was a simple renal cyst. The mean follow-up was 35.8 months. At the end of follow-up, the cyst units were reduced in size by more than 50% compared to the preoperative size, and no patient experienced a recurrence. Conclusion: Multi-level paravertebral nerve block for percutaneous ureteroscopy laser unroofing as an ambulatory surgery mode is feasible, safe, and effective for the treatment of simple renal cysts in selected patients.

Objective: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. Methods: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone

Thermal insulation is crucially important to the safety and reusability of aerospace vehicles. Fabrication of thermal insulation materials with light weight, high mechanical strength and low thermal conductivity remains challenging. In this study, porous polymer derived silicon oxycarbide (SiOC) ceramics with hierarchical structures mimicking cuttlebones were prepared through stereolithography additive manufacturing followed by pyrolysis. The compressive strength of SiOC ceramics with ridges (“R” structures) alongside the sinusoidal walls (“S” structures) (RS-SiOC, 13.37 ± 0.86 MPa for 7-RS-SiOC) mimicking those of cuttlebone was much higher than that of SiOC ceramics with just sinusoidal walls (S–SiOC, 8.43 ± 0.81 MPa), while the density of RS-SiOC with 7 ridges (7-RS-SiOC) and S–SiOC were 0.40 g/cm3 and 0.39 g/cm3, respectively. Our results revealed that the tailored “S” and “R” structures of biomimetic 7-RS-SiOC ceramics, together with the amorphous network of SiOC assembled in the layer-by-layer manner, rendered the high mechanical strength. In addition, the 7-RS-SiOC sample exhibited a low thermal conductivity of 0.12 W/(m·K) at room temperature. The back temperature of the 7-RS-SiOC sample was 179.5 °C when exposed to 800 °C for 1200 s, showing excellent thermal insulation capability. The state-of-the-art biomimetic design of lightweight SiOC ceramics likely offers a solution to high-performance thermal insulation for aerospace vehicles.

Abstract Exosomes are lipid bilayer vesicles with a diameter of 40–100 nm secreted by almost all cells. They have been found play crucial regulatory roles in various diseases. With the development of exosomes engineering technology, exosome-based drug delivery has also rapidly evolved. Bladder cancer is a worldwide disease with high morbidity and recurrence but lack of funding, so it is also called Cinderella. Some explorations have demonstrated that exosomes are important in the development, prognosis, diagnosis and drug delivery of bladder cancer. With the rapid development of Mass spectrometry and next-generation sequencing, increasing numbers of differentially expressed molecules derived from exosomes have been found in bladder cancer. Exosomes and their contents are largely involved in bladder cancer progression, engineering of these exosomes with the targeted genes improves their potential for drug delivery of bladder cancer. Furthermore, exosomes and their contents are relate to many characteristics of bladder cancer. Herein, we briefly search 59 researches to explore the cargoes encapsuled in exosomes of bladder cancer patients. We also summarize the biogenesis, function, expression profiles, engineering approaches and biological mechanisms of exosomes and their contents for the diagnosis, prognosis and drug delivery for bladder cancer. We aim to make it clear whether exosomes are the glass slippers of Cinderella. Graphical Abstract

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.

In this paper, Al-Mg-Si alloys with a thickness of 4 mm are welded by using laser beam welding (LBW) and laser-MIG hybrid welding, respectively, and the microstructure and mechanical properties of the two joints are investigated. The results show that the fusion zone (FZ) of the two joints is composed of columnar crystal and equiaxed dendrite grain, and its main constituent phases are an α-Al matrix phase and a β(Mg2Si) strengthening phase. In the case of similar heat inputs, compared with those of the LBW joint, the grain size in the laser-MIG hybrid joint is smaller and there are more second phases such as the β phase in the FZ, which is related to the different action mechanisms on the base metal (BM) by the two welding processes. Under the three strengthening mechanisms of fine grain strengthening, precipitation strengthening, and solid solution strengthening, the laser-MIG hybrid welding joint shows better mechanical properties than that of the LBW joint. The maximum tensile strength of the LBW joint and the laser-MIG hybrid joint is 202 MPa and 253 MPa, respectively, and the elongation is 3.8% and 5.1%, respectively.

Abstract Background Non-invasive risk stratification contributes to the precise treatment of prostate cancer (PCa). In previous studies, lymphocyte subsets were used to differentiate between low-/intermediate-risk and high-risk PCa, with limited clinical value and poor interpretability. Based on functional subsets of peripheral lymphocyte with the largest sample size to date, this study aims to construct an easy-to-use and robust nomogram to guide the tripartite risk stratifications for PCa. Methods We retrospectively collected data from 2039 PCa and benign prostate disease (BPD) patients with 42 clinical characteristics on functional subsets of peripheral lymphocyte. After quality control and feature selection, clinical data with the optimal feature subset were utilized for the 10-fold cross-validation of five Machine Learning (ML) models for the task of predicting low-, intermediate- and high-risk stratification of PCa. Then, a novel clinic-ML nomogram was constructed using probabilistic predictions of the trained ML models via the combination of a multivariable Ordinal Logistic Regression analysis and the proposed feature mapping algorithm. Results 197 PCa patients, including 56 BPD, were enrolled in the study. An optimal subset with nine clinical features was selected. Compared with the best ML model and the clinic nomogram, the clinic-ML nomogram achieved the superior performance with a sensitivity of 0.713 (95% CI 0.573–0.853), specificity of 0.869 (95% CI 0.764–0.974), F1 of 0.699 (95% CI 0.557–0.841), and AUC of 0.864 (95% CI 0.794–0.935). The calibration curve and Decision Curve Analysis (DCA) indicated the predictive capacity and net benefits of the clinic-ML nomogram were improved. Conclusion Combining the interpretability and simplicity of a nomogram with the efficacy and robustness of ML models, the proposed clinic-ML nomogram can serve as an insight tool for preoperative assessment of PCa risk stratifications, and could provide essential information for the individual diagnosis and treatment in PCa patients.

Abstract Bioinspired nacre-like structures are effective in toughening materials, yet are difficult to construct in magnesium-ceramic systems. Here, a set of magnesium-MAX phase composites with nacre-like lamellar and brick-and-mortar architectures are fabricated by pressureless infiltration of the magnesium melt into ice-templated Ti3AlC2 ceramic scaffolds. The structure and mechanical properties of the composites are elucidated with a special focus on the effects of the types of architectures (lamellar or brick-and-mortar) and matrices (pure magnesium or AZ91D alloy) on the toughening mechanisms. The nacre-like architectures are found to play a role in blunting the cracks via plastic deformation and microcracking, and shielding the cracks from applied stress by promoting crack deflection and uncracked-ligament bridging mechanisms. These composites achieve a good combination of specific strength and fracture toughness, which are superior to many other reported magnesium-ceramic and nacre-like metal-ceramic composite materials.

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions: RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Natural fish scales demonstrate outstanding mechanical efficiency owing to their elaborate architectures and thereby may serve as ideal prototypes for the architectural design of man-made materials. Here bioinspired magnesium composites with fish-scale-like orthogonal plywood and double-Bouligand architectures were developed by pressureless infiltration of a magnesium melt into the woven contextures of continuous titanium fibers. The composites exhibit enhanced strength and work-hardening ability compared to those estimated from a simple mixture of their constituents at ambient to elevated temperatures. In particular, the double-Bouligand architecture can effectively deflect cracking paths, alleviate strain localization, and adaptively reorient titanium fibers within the magnesium matrix during the deformation of the composite, representing a successful implementation of the property-optimizing mechanisms in fish scales. The strength of the composites, specifically the effect of their bioinspired architectures, was interpreted based on the adaptation of classical laminate theory. This study may offer a feasible approach for developing new bioinspired metal-matrix composites with improved performance and provide theoretical guidance for their architectural designs.

Background: Kidney stone disease is a global disease; however, it has not been totally understood. Calcium oxalate (CaOx) stone is the dominant type of kidney stone, and the potential factors involved in its formation are yet to be explored. Clinically, we found that the CaOx stones in patients were mainly unilateral; therefore, systemic factors cannot explain them, although some local factors must be involved. Urinary microbiota is involved in stone formation. Therefore, this study aimed to explore the association between the urinary microbiota and CaOx stones and provide insight into the medical treatment and prevention of CaOx stones.Methods: Sixteen pelvic urine samples were collected from the stone and non-stone sides of patients with unilateral CaOx stones following strict criteria. The 16S rRNA gene sequencing was performed on each pair of pelvic urine samples at the species level. Many bioinformatic analyses were conducted to explore the potential factors affecting CaOx stone formation.Results: Although no statistically significant difference was found between the overall microbiota of the pelvis urine from the two sides. Many biologically distinct taxa were observed, including many bacteria found in previous studies, like Proteobacteria, Actinobacteria, Firmicute and Enterobacter cloacae and so on. What’s more, despite these common bacteria, our current study added to these bacterial communities with additional identification of Deinococcus-Thermus, Coriobacteriia, Porphyromonas and Ralstonia. To predict the functions of these microbiota, Kyoto Encyclopedia for Genes and Genomes and MetaCyc analysis were conducted and immunometabolism might be an important pathway. Moreover, a random forest predictor was constructed to distinguish the stone side from the non-stone side, with an accuracy of 62.5%.Conclusion: Our research profiled the microbiome in the pelvis urine from both the stone and non-stone sides of patients with unilateral CaOx stones, provided insight into the dominant role of urinary dysbiosis in CaOx stones formation. Furthermore, this study also predicted the potential crosstalk among urinary microbiota, immunometabolism, and CaOx stones.

Abstract Background Calcium oxalate (CaOx) stone disease is found worldwide. To explore the role of exosomes as a mediator of intercellular crosstalk during CaOx stone formation, we conducted this study, which may provide a new insight into the treatment and prevention of CaOx stones. Methods Exosomes derived from HK2 cells with (EXO(S)) or without (EXO(C))CaOx crystal stimulation were cocultured with normal tubular epithelial cells and subcapsularly injected into rat kidneys. Then, oxidative stress levels, the MAPK signalling pathway and osteogenic changes were detected via qPCR, Western blotting, immunofluorescence and immunohistochemical staining. In vivo fluorescence imaging and exosome internalization assays showed the absorption and utilization of exosomes. Results EXO(S) increased the reactive oxygen species (ROS) level and activated the expression of BMP2, OPN and OCN via the MAPK/P-38 pathway both in vivo and in vitro. In vivo experiments showed that preinjection of EXO(S) aggravated, while preinjection of EXO(C) ameliorated, these effects. Crystal depositions were significantly increased in SD rats injected with GAM when they were preinjected with EXO(S), and these effects could be reversed after preinjection with EXO(C). Conclusion Our study revealed that exosome-mediated intercellular crosstalk could accelerate the formation of CaOx stones by promoting oxidative stress and the osteogenic cascade in normal tubular epithelial cells. Graphical Abstract HK2 cells stimulated with CaOx crystals released more exosomal miR-223-3p and S100A8 comparing with normal HK2 cells. These exosomes derived from HK2 cells stimulated with CaOx (EXO(S)) could amplify the oxidative stress and osteogenic changes via MAPK/P-38 pathway, which finally led to the formation of Randall’s plaque.

Purpose: To determine whether microRNA could be a therapy target of erectile dysfunction (ED) and the underlying mechanisms. Materials and Methods: Eight-week-old fasting male SD rats were intraperitoneally injected with streptozotocin to construct diabetic rat models. Diabetic ED rats were treated with miRNA-92a inhibitor. The cavernous nerves were electrically stimulated to measure the intracavernous pressure and mean arterial pressure of rats in each group. After the detection, the penile cavernous tissues are properly stored for subsequent experiments. Rat aortic endothelial cells were used in in vitro studies. Results:The expression of miR-92a was significantly increased in the corpus cavernosum of Streptozocin (STZ)-induced diabetic rats and injection of miR-92a antagomir into the corpus cavernosum of diabetic rats significantly increased eNOS/NO/ cGMP signaling pathway activities, cavernous endothelial cell proliferation, endothelial cell-cell junction protein expression and decreased the levels of oxidative stress. These changes restored erectile function in STZ-induced diabetic rats. Moreover, in vitro study demonstrated that the miR-92a expression increased significantly in endothelial cells treated with high glucose, inhibiting AMPK/eNOS and AMPK/Nrf2/HO-1 signaling pathways in rat aortic endothelial cells via targeting Prkaa2, causing endothelial dysfunction and overactive oxidative stress, miR-92a inhibitor can improve the above parameters. Conclusions: miRNA-92a inhibitor could exert an inhibition role on oxidative stress and endothelial dysfunction to improve diabetic ED effectively.

Recent studies suggest that cancer stemness drives the acquired drug resistance process in cancer therapy. The complementary information provided by multi-omics data can help us to gain a deeper understanding of this process. This study aims to elucidate the impact of cancer stemness on the frontline treatment of clear cell renal cell carcinoma (ccRCC). Consensus clustering based on stem/progenitor signatures refined 3 subgroups in 1,730 tumor samples. We identified master regulons that regulate cancer stemness phenotypes, including key transcription factors, DNA methyltransferases, and promoter methylation probes. In addition, we compared the clinicopathological traits, genomic heterogeneity, cancer hallmarks, tumor microenvironment (TME), and oncological prognosis of the stemness subgroups. Cancer stemness was correlated with reduced efficiency of immune checkpoint blockade therapy. Cancer stemness profoundly affects the prognosis and treatment outcome of ccRCC by increasing genomic instability, tumor-associated malignant events, and immunosuppressive factors. For clinical application, we established and validated a 243-gene signature from stem/progenitor-related genes to distinguish anti-PD-1 outcomes. Overall, this presented study suggested that cancer stemness leads to adaptive resistance to anti-PD-1 treatment in CD8+ T-infiltrated ccRCC and provides a new reference for strategy development to further improve immunotherapy response rates.

Abstract There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole‐exome sequencing on normal‐tumor‐thrombus‐metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C‐index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501–0.610, 0.667 versus 0.544–0.651, and 0.719 versus 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively). We constructed a risk predicting model, TT‐GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT‐GPS score displayed better discriminatory ability (OS, c‐index: 0.706–0.840, AUC: 0.788–0.874; DFS, c‐index: 0.691–0.717, AUC: 0.771–0.789) than previously reported models in risk assessment. In conclusion, we identified for the first‐time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT‐GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

BackgroundPsychological stress and its two stress response systems, the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), are closely related to psychogenic erectile dysfunction (pED). However, the analyses of perceived stress and stress systems in pED patients need to be more in-depth, especially the interactions between them.MethodsOur study included 75 patients with pEDs and 75 healthy men. The International Index of Erectile Function-5 (IIEF-5) and the 10-item Perceived Stress Scale (PSS-10) were used for assessing the severity of ED and perceived stress. All participants collected saliva samples on three consecutive days at eight specific times with strict reference to the time of morning awakening for measuring cortisol parameters and wore electrocardiography for 24 h to derive heart rate variability (HRV).ResultsThe PSS-10 scores of pED patients were significantly higher than the control group (p0.05). The interaction between sympathovagal modulation (HF, rMSSD) and cortisol awakening response (CAR AUCi) explained significantly greater variance in perceived stress than either stress system alone. Higher parasympathetic activity combined with a higher cortisol awakening response was associated with greater perceived stress.ConclusionOur results suggested that the interrelation between ANS and HPA axis activity might enhance our comprehension of how stress affected the physical and mental health of pED patients.

Abstract Background Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic neoplastic disorder caused by germline mutation or deletion of the VHL gene, characterized by the tendency to develop multisystem benign or malignant tumors. The mechanism of VHL mutants in pathogenicity is poorly understand. Results Here we identified heterozygous missense mutations c.193T > C and c.194C > G in VHL in several patients from two Chinese families. These mutations are predicted to cause Serine (c.193T > C) to Proline and Tryptophan (c.194C > G) substitution at residue 65 of VHL protein (p.Ser65Pro and Ser65Trp). Ser65 residue, located within the β-domain and nearby the interaction sites with hypoxia-inducing factor α (HIFα), is highly conserved among different species. We observed gain of functions in VHL mutations, thereby stabilizing HIF2α protein and reprograming HIF2α genome-wide target gene transcriptional programs. Further analysis of independent cohorts of patients with renal carcinoma revealed specific HIF2α gene expression signatures in the context of VHL Ser65Pro or Ser65Trp mutation, showing high correlations with hypoxia and epithelial-mesenchymal transition signaling activities and strong associations with poor prognosis. Conclusions Together, our findings highlight the crucial role of pVHL-HIF dysregulation in VHL disease and strengthen the clinical relevance and significance of the missense mutations of Ser65 residue in pVHL in the familial VHL disease.

BackgroundInformation from the RENAL score is limited. This study aimed to identify new parameters based on three-dimensional (3D) reconstruction of preoperative enhanced computerized tomography (CT) for predicting outcomes after robot-assisted partial nephrectomy (RPN).Materials and methodsThe records of kidney cancer patients who underwent RPN at Tongji Hospital from March 2015 to July 2019 were reviewed. Demographic data, laboratory examinations, postoperative hospitalization time, and enhanced CT were retrospectively collected. Some tumor parameters were obtained from 3D reconstruction of CT data. The association between these predictive factors and outcomes after RPN was analyzed.ResultsA larger tumor bed area (TBA) was associated with a longer warm ischemia time (WIT) (P-value

Background: To evaluate the safety, efficacy and cost of paravertebral block anesthesia for ureteral stones patients undergoing ureteroscopic lithotripsy. Methods: Four hundred and eighty-two patients who underwent ureteroscopy for unilateral ureteral stones were incorporated into our retrospective study. A propensity-matched comparison in patients with paravertebral nerve block anesthesia (PVB) group and general anesthesia (GA) group was performed. Intraoperative hemodynamic parameters, operative time, visual analog scale for pain, stone-free rate, anesthetic cost and postoperative hospital stay were compared between the two groups. Results: Sixty-one GA cases were propensity matched to 61 PVB cases. In the PVB group, all the procedures were completed successfully without anesthesia conversion. Significantly less intraoperative severe hypotensive (P = 0.002) and arrhythmia (P

Purpose: Pulsatile gonadotropin-releasing hormone (GnRH) therapy and gonadotropin therapy (GT) were widely used for male patients with congenital hypogonadotropic hypogonadism (CHH), but their efficacy was not well compared before. We conducted this meta-analysis to compare the efficacy of restoring fertility using these two therapies. Materials and Methods: PubMed, Web of Science, and Scopus were systematically searched for comparative studies evaluating the efficiency of GnRH therapy and GT for male patients with CHH. For continuous outcomes, the weighted mean difference (WMD) was used to measure the difference, whereas the risk ratio with 95% confidence interval was calculated for binary variables. Results: Overall, eight articles from seven studies with 420 patients enrolled were included in the analysis. Patients from the two different groups were determined to be comparable in age, proportion with Kallmann syndrome, percentage of cryptorchidism and pretreatment hormones (follicular-stimulating hormone, luteinizing hormone, and testosterone). GnRH therapy was related to a larger testicular volume (standardized mean difference=-1.43; p=0.01) and earlier spermatogenesis (WMD=- 5.30 months; p=0.004) compared to GT. However, the difference in the rate of positive sperm detection (p=0.08), sperm concentration (p=0.37), and pregnancy rate (p=0.11) were not significant. Allergic reactions mostly occurred during GnRH therapy, while GT was related to a higher incidence of gynecomastia and acne. Conclusions: Compared to GT, GnRH was related to earlier spermatogenesis and less estradiol-related adverse reactions, although there were no significant differences in spermatogenesis rate, sperm concentration, and pregnancy rate. High-quality randomized controlled trials are needed for future research.

Abstract Background The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable mortality. The risk factors, clinical treatments, especially comprehensive risk models for COVID-19 death are urgently warranted. Methods In this retrospective study, 281 non-survivors and 712 survivors with propensity score matching by age, sex, and comorbidities were enrolled from January 13, 2020 to March 31, 2020. Results Higher SOFA, qSOFA, APACHE II and SIRS scores, hypoxia, elevated inflammatory cytokines, multi-organ dysfunction, decreased immune cell subsets, and complications were significantly associated with the higher COVID-19 death risk. In addition to traditional predictors for death risk, including APACHE II (AUC = 0.83), SIRS (AUC = 0.75), SOFA (AUC = 0.70) and qSOFA scores (AUC = 0.61), another four prediction models that included immune cells subsets (AUC = 0.90), multiple organ damage biomarkers (AUC = 0.89), complications (AUC = 0.88) and inflammatory-related indexes (AUC = 0.75) were established. Additionally, the predictive accuracy of combining these risk factors (AUC = 0.950) was also significantly higher than that of each risk group alone, which was significant for early clinical management for COVID-19. Conclusions The potential risk factors could help to predict the clinical prognosis of COVID-19 patients at an early stage. The combined model might be more suitable for the death risk evaluation of COVID-19.

BackgroundMental stress and imbalance of its two neural stress systems, the autonomic nervous system (ANS) and the hypothalamic–pituitary–adrenal (HPA) axis, are associated with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED). However, the comprehensive analyses of psychological stress and stress systems are under-investigated, particularly in CP/CPPS patients complicated by lower urinary tract symptoms (LUTS) and ED.Materials and methodsParticipants were 95 patients in CP/CPPS+ED group, 290 patients in CP/CPPS group, 124 patients in ED group and 52 healthy men in control group. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function-5 (IIEF-5) and the International Prostate Symptom Score (IPSS) were used for assessing the disease severity of CP/CPPS, LUTS and ED. Psychometric self-report questionnaires including the Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS), Type A Personality Test (TAPT) and Symptom Checklist 90 (SCL-90) were completed for distress from physical symptoms. Twenty-five subjects per group were randomly selected for further investigating the changes of the HPA axis and ANS. Saliva samples were taken on 3 consecutive days at 8 specific times with strict reference to time of morning awakening for evaluation of free cortisol. Heart rate variability (HRV) as marker of the ANS was measured using 24 h electrocardiography, and time-and frequency-domain variables were analyzed.ResultsThe BAI and SCL-90 scores were significantly higher in the CP/CPPS+ED, CP/CPPS and ED groups compared with the control group (p

Background Calcium oxalate (CaOx) is the most common type of kidney stone, but the mechanism of CaOx stones formation remains unclear. The injury of renal cells such as ferroptosis and autophagy has been considered a basis for stones formation. Methods We conducted transmission electron microscope (TEM), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and C11-BODIPY analysis to explore whether CaOx could induce autophagy-dependent ferroptosis in vivo and in vitro. To explore the possible mechanism, we conducted bioinformatic analysis of patients with or without CaOx stones, Western blot and qPCR were used to identify the different genes we found in bioinformatic analysis. Results In our study, we found that CaOx could induce autophagy-dependent ferroptosis no matter in vivo or in vitro, which might finally lead to urolithiasis. Bioinformatic analysis of the GSE73680 dataset indicated that the expression of caveolin-1 (CAV1) was higher in control patients than CaOx stone patients, the STRING database indicated that CAV1 might interact with low density lipoprotein receptro-related protein 6 (LRP6), Gene Set Enrichment Analysis (GSEA) showed that the WNT pathway positively associated with the control group while negatively related to the stone group, and LRP6 was the core gene of the WNT pathway. Western blot found that CAV1, LRP6, and Wnt/β-Catenin were decreased in Human Kidney2 (HK2) cells stimulated with CaOx. Furthermore, the WNT pathway was considered to be involved in autophagy and ferroptosis. Conclusions We presumed that CAV1 could ameliorate autophagy-dependent ferroptosis through the LRP6/Wnt/β-Catenin axis, and finally alleviate CaOx stone formation.

Prostate cancer is the third leading cause of new cancer cases and the second most common tumor type in men globally. LMO3 has been stated to play a vital role in some cancers; however, the prognostic value of LMO3 in PCa remains vague. Here, we utilized various web databases to elucidate in detail the prognostic value and molecular functions of LMO3 in PCa. LMO3 expression was significantly decreased in PCa. Low LMO3 expression was associated with gender, age, and TNM grade and predicted a poor prognosis in PCa patients. Functional enrichment analysis suggested that LMO3 is engaged in the extracellular matrix and immune response. Moreover, LMO3 was positively correlated with immune infiltration levels and numerous immune markers. LMO3 may function as a prospective biomarker of immune infiltration in PCa.

Background: Calcium oxalate kidney stone is one of the common diseases in the urinary system and has a high recurrence rate. Currently, the pathogenesis of kidney stone and the methods to prevent recurrence are still being investigated. Autophagy, as an event of cellular self-repair, has received attention in the field of kidney stone in recent years. In some current studies, autophagy has shown destructiveness and protectiveness in the pathogenesis of kidney stone. The inhibition or promotion of autophagy may be a key target for future kidney stone therapy. This systematic literature review discusses the function of autophagy in kidney stone pathogenesis in the context of current research and synthesizes the evidence analysis to provide a basis for new future therapies.Method: We systematically reviewed the literature during September 2021 according to the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) guidelines. Articles on studying the role of autophagy in the pathogenesis of calcium oxalate kidney stone were extracted from PubMed, MEDLINE, Embase and Scopus, including in vivo versus in vitro experiments. The study topic, language and publication date were not restricted. Two authors (Li and Zhou) searched and screened the literature.Results: We screened 18 articles from the 33 collected articles, of which 6 conducted in vitro cellular studies, four conducted animal studies, eight conducted cellular studies with animal studies, and five studied human specimens. In early studies, the literature generally concluded that autophagy is deleterious in the development of kidney stone. In 2020, the idea of the protectiveness of autophagy associated with kidney stone was first proposed and focused on targeting transcription factor EB. In addition, the interaction of autophagy with other cellular events and the regulation of signaling molecules are focused on in this paper.Conclusion: This systematic review provides advances in research on the role of autophagy in renal calculi. The current studies suggest that both upregulation and downregulation of autophagy may ameliorate injury in kidney stone models. The authors prefer the upregulation of autophagy as a future research direction for kidney stone treatment.

Kidney renal clear cell carcinoma (KIRC) is a heterogeneous malignant tumor with high incidence, metastasis, and mortality. The imbalance of copper homeostasis can produce cytotoxicity and cause cell damage. At the same time, copper can also induce tumor cell death and inhibit tumor transformation. The latest research found that this copper-induced cell death is different from the known cell death pathway, so it is defined as cuproptosis. We included 539 KIRC samples and 72 normal tissues from the Cancer Genome Atlas (TCGA) in our study. After identifying long non-coding RNAs (lncRNAs) significantly associated with cuproptosis, we clustered 526 KIRC samples based on the prognostic lncRNAs and obtained two different patterns (Cuproptosis.C1 and C2). C1 indicated an obviously worse prognostic outcome and possessed a higher immune score and immune cell infiltration level. Moreover, a prognosis signature (CRGscore) was constructed to effectively and accurately evaluate the overall survival (OS) of KIRC patients. There were significant differences in tumor immune microenvironment (TIME) and tumor mutation burden (TMB) between CRGscore-defined groups. CRGscore also has the potential to predict medicine efficacy.

Androgen receptor (AR) is the principal molecule in prostate cancer (PCa) etiology and therapy. AR re‐activation still remains a major challenge during treatment of castration‐resistant prostate cancer (CRPC) tumors that relapse after castration therapies. Recent reports have indicated the enrichment of Ser81‐phosphorylated AR (pS81) in the nucleus of CRPC cells, and CDK1 and CDK9 as the kinases phosphorylating AR at S81. In the current study we showed that pS81 is preferentially localized in the nucleus in both rapid biopsy metastatic CRPC samples and PCa xenografts, and nuclear pS81 localization is correlated with AR transactivation in tumor xenografts. Chromatin immunoprecipitation (ChIP) analysis demonstrated an alignment of S81 phosphorylation and AR‐mediated transactivation with the chromatin locus openness. Moreover, pS81‐specific ChIP‐Seq showed a disproportional occupancy of pS81 on AR‐activated promoters, while 3C‐ChIP assays further indicated an enrichment of pS81 at the PSA enhancer‐promoter loop, a known AR activating hub. In the latter, CDK9 was shown to modulate the transactivation of the AR and RNA Pol II. Indeed, ChIP and re‐ChIP assays also confirmed that AR‐dependent activation of the PSA enhancer and promoter mediated by pS81 was coupled with activation of Pol II and the pTEFb complex. Mechanistically, we determined that CDK1 and CDK9 sustained the pS81 AR modification in the soluble and chromatin‐bound fractions of PCa cells, respectively. Finally, we demonstrated that CDK1 activity was maintained throughout the cell cycle, and that CDK1 inhibitors restored androgen sensitivity in CRPC tumor cells. Based on these findings, CDK1 and CDK9 could be targeted as pS81 kinases in patients with CRPC, either alone or in conjunction with direct AR antagonists.

Post-translational modifications of tubulins regulate microtubule properties and neural development. Here, the authors report that one such post-translational modification, α-TubK40me3, is required for neuronal polarization and migration by promoting microtubule formation.

BackgroundCisplatin-based neoadjuvant chemotherapy combined with radical cystectomy (RC) plus pelvic lymph node dissection (PLND) is the preferred treatment option for muscle-invasive bladder cancer (MIBC). However, some patients are unable to tolerate RC or may have postoperative complications after RC. And most patients have a strong desire for bladder-preserving treatment. There are no reports on the efficacy of maximal transurethral resection of the bladder tumor (TURBT) in combination with chemotherapy plus tislelizumab for bladder-preserving in recurrent MIBC patients.Case presentationWe report two cases diagnosed with recurrent MIBC who achieved pathological complete response (pCR) and bladder-preserving after maximal TURBT combined with chemotherapy plus tislelizumab.ConclusionPostoperative immunotherapy should be considered for all patients with recurrent MIBC who are eligible for immunotherapy. In addition, high programmed death ligand-1 (PD-L1) expression, high tumor mutation burden (TMB), and TP53 mutation level can be combined to predict tislelizumab efficacy.

Accumulating evidence has suggested the impact of senescence on tumor progression, but no report has yet described how senescence shapes the tumor microenvironment of clear cell renal cell carcinoma (ccRCC). The objective of this study was to delineate the senescence features of ccRCC and its role in shaping the tumor microenvironment through a comprehensive analysis of multiple datasets, including 2,072 ccRCC samples. Unsupervised consensus clustering identified three senescence subtypes, and we found that the senescence-activated subtype survived the worst, even in the condition of targeted therapy and immunotherapy. The activated senescence program was correlated to increased genomic instability, unbalanced PBMR1/BAP1 mutations, elevated immune cell infiltration, and enhanced immune inhibitory factors (cancer-associated fibroblasts, immune suppression, immune exclusion, and immune exhaustion signaling). A senescence score based on nine senescence-related genes (i.e., P3H1, PROX1, HJURP, HK3, CDKN1A, AR, VENTX, MAGOHB, and MAP2K6) was identified by adaptive lasso regression and showed robust prognostic predictive power in development and external validation cohorts. Notably, we found that the senescence score was correlated to immune suppression, and the low-score subgroup was predicted to respond to anti–PD-1 therapy, whereas the high-score subgroup was predicted to respond to Sunitinib/Everolimus treatment. Collectively, senescence acted as an active cancer hallmark of ccRCC, shaped the immune microenvironment, and profoundly affected tumor prognosis and drug treatment response.

Abstract Background To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP). Methods We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort. Results In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020). Conclusion The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.

Prostate cancer (PCa) has a high incidence rate, mortality rate, and biochemical recurrence (BCR) rate. 7-Methylguanosine (m7G), as one of the RNA modifications, has been considered to be actively involved in cancer-related translation disorders in recent years. Therefore, we first used The Cancer Genome Atlas (TCGA) database to identify prognosis and m7G-related long non-coding RNAs (lncRNAs). Then we randomly divided the samples into the training set and test set and then constructed and verified the m7G lnRNA prognostic model (m7Gscore) by the least absolute shrinkage and selection operator (LASSO) regression analysis. The m7Gscore has been proved to be an independent marker of BCR-free survival in patients with PCa. Furthermore, the m7Gscore was significantly correlated with the tumor immune microenvironment (TIME) and somatic mutation of PCa patients and had the potential to be an indicator for the selection of drug treatment. We also clustered TCGA cohort into three m7G-related patterns (C1, C2, and C3). The Kaplan–Meier survival analysis revealed that C1 had the best BCR-free survival and C3 had the worst. The TIME was also significantly distinct among the three m7G-related patterns. According to the TIME characteristics of the patterns, we defined C1, C2, and C3 as immune-desert phenotype, immune-inflamed phenotype, and immune-excluded phenotype, respectively.

ObjectiveRenal collecting duct carcinoma (CDC) is an extremely rare disease with few studies, and the current understanding of its prognosis is limited. We used the Surveillance, Epidemiology, and End Results (SEER) registry data to explore the prognostic factors and effect of treatment modalities on the overall survival (OS) and cancer-specific survival (CSS) in patients with CDC.MethodsPatients’ information of CDCs diagnosed by pathological examination between 2000 and 2018 was extracted from the SEER database. The Kaplan–Meier method was used to calculate OS and CSS and log-rank tests to evaluate the differences in OS and CSS. The associations between clinicopathological variables and survival outcomes were assessed with the Cox proportional hazard model. A directed acyclic graph (DAG) was drawn to recognize confounding factors and to obtain the multivariable regression model, and the impact of surgery, radiotherapy, and chemotherapy on OS and CSS was analyzed, respectively.ResultsA total of 242 patients with CDC were enrolled. The median OS and CSS time were 17 and 21 months, respectively. The OS rates at 1, 2, and 5 years were 56.9%, 41.9%, and 30.0%, respectively, while the CSS rates at 1, 2, and 5 years were 60.1%, 47.5%, and 34.8%, respectively. Patients who had a large tumor size, poor pathological grade, and advanced TNM classification exhibited worse survival outcomes. Univariable and multivariable Cox regression analyses revealed that surgery, chemotherapy, T stage, N stage, and M stage were independent prognostic factors for OS and CSS. The DAG-guided multivariate Cox regression model revealed that surgery and chemotherapy improved OS and CSS.ConclusionsCDC is an exceedingly rare disease and has malignant behavior. Most patients have a high pathological grade and advanced TNM stage at diagnosis and exhibited poor survival. Resection of all visible tumors including metastatic lesions or chemotherapy can be beneficial to prognosis, while healthier benefits are less likely to receive radiotherapy. More relevant studies with larger samples are needed to verify the value of surgery and adjuvant therapy in the treatment of CDCs.

Background: Emerging asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were detected and multiple cases were found to be SARS-CoV-2 positive again, which raised an alarm for the patients hospitalized after the coronavirus disease 2019 (COVID-19) pandemic. Objective: We investigated the risk and prevention of hospital transmission of SARS-CoV-2 to hospitalized urological patients. Design, setting, and participants: This is a retrospective study of 319 hospitalized urological patients enrolled between April 20, 2020 and May 11, 2020 from two tertiary hospitals in Wuhan, China. Intervention: Chest computed tomography (CT) images, nucleic acid tests (NATs), and serum antibody were examined at the outpatient department and 1 wk after admission for all patients. Outcome measurements and statistical analysis: The chest CT images, NATs, serum antibody results, and clinical data were collected and analyzed. Results and limitations: None of the 319 patients was found to be SARS-CoV-2 NAT positive. Ten and four patients were detected to be immunoglobulin (Ig)G and IgM positive, respectively. The chest CT features of 116 patients showed abnormal lung findings. During the 1-wk isolation, one patient initially being IgG positive only was found to be IgM positive, and another initially IgM-positive patient had a rising IgG level. Through risk assessment, we identified seven patients with very high and high risk for hospital transmission, and delayed the surgery while maintaining close follow-up. Five intermediate-risk patients were operated on successfully under paravertebral block or epidural anesthesia to avoid opening the airway with endotracheal intubation. The remaining 104 low-risk and 203 normal patients underwent normal surgery. Conclusions: Of the 319 patients, seven were identified as very high and high risk, which reinforced the importance of epidemic surveillance of discharged COVID-19 patients and asymptomatic infections. Five intermediate-risk patients were operated on successfully under regional anesthesia. Patient summary: Our experience of risk assessment and management practice may provide a strategy to prevent severe acute respiratory syndrome coronavirus 2 transmission to hospitalized urological patients after the coronavirus disease 2019 (COVID-19) pandemic.

Objective: To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy (MIRC) or open radical cystectomy (ORC). Methods: We identified patients with bladder cancer who underwent radical cystectomy (RC) in 13 centers of the Chinese Bladder Cancer Consortium (CBCC). Perioperative outcomes were compared between MIRC and ORC. The influence of surgical approaches on overall survival (OS) and cancer-specific survival (CSS) in the entire study group and subgroups classified according to pathologic stage or lymph node (LN) status was assessed with the log-rank test. Multivariable Cox proportional hazard models were used to evaluate the association among OS, CSS and risk factors of interest. Results: Of 2 098 patients who underwent RC, 1 243 patients underwent MIRC (1 087 laparoscopic RC and 156 robotic-assisted RC, respectively), while 855 patients underwent ORC. No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate. MIRC was associated with less estimated blood loss, more LN yield, higher rate of neobladder diversion, longer operative time, and longer length of hospital stay. There was no significant difference in OS and CSS according to surgical approaches (p=0.653, and 0.816, respectively). Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement. Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS. Conclusions: Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

Abstract 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

Summary: Objective: To report our experience in treating endophytic renal tumor by robot-assisted partial nephrectomy (RPN) with a standard laparoscopic ultrasound probe and our original approach for separating renal mass. Methods: All patients with endophytic renal tumor who underwent RPN in our department from January 2015 to December 2017 were retrospectively analyzed. All surgeries were performed by transperitoneally by a single, experienced surgeon. Baseline characteristics, tumor characteristics, operative profile and follow-up data were collected. Results: Among these 29 patients, 23 patients were male. The mean age of patients was 47.42 years old. 69% (20/29) tumors were completely endophytic tumors. The average tumor size was 3.1 cm. The average R.E.N.A.L. score was 9.0. Tumors from 3 patients were pathologically confirmed to be renal angiomyolipomas. And the rest were malignant including 23 clear cell renal cell carcinoma and 3 chromophobe renal cell carcinoma. The mean operative time was 3.0 h. The mean warm ischemia time was 22.3 min. All tumor margins were pathologically confirmed negative. No patient needed blood transfusion. Two patients presented had Grade II complication. Both of them had a fever after surgery with body temperature over 38 °C, leading to a prolonged postoperative hospitalization time. The mean postoperative hospitalization time was 6.8 days. During mean 21.3-month follow-up, no patient was confirmed to relapse by CT scan. Conclusion: RPN with a standard laparoscopic ultrasound probe is safe, effective and feasible in treating endophytic renal tumor. Our original approach for separating renal mass can avoid some problems caused by the standard laparoscopic ultrasound probe. Keywords: Robot-assisted partial nephrectomy, Standard laparoscopic ultrasound probe, Retrospective study

Objective: To present our experience and technique with robot-assisted ureteroneocystostomy (RAUN) procedure in adults. Methods: Between February 2015 and August 2018, a total of 30 (34 ureters) patients who underwent RAUN surgery under a single surgeon were retrospectively reviewed. Perioperative data such as age, sex, body mass index (BMI), American society of anesthesiologists score, estimated blood loss, surgical technique, operative time, complications, length of hospital stay, and stent removal time were recorded. During the follow-up, patients underwent renal function test, urinalysis, and renal ultrasound examination for evaluation. Success was defined as symptomatic and radiologic relieve. Lastly, a literature search was conducted to review all published articles regarding RAUN surgery in adults. Results: The patients’ mean age, BMI, EBL, operative time, and follow-up period were 45.4 years, 23.1 kg/m2, 65.6 mL, 182.9 min, and 21.3 months, respectively. The two most common indications for the surgery were benign ureteral strictures and ureteric injuries secondary to a previous radical hysterectomy. Of the 34 cases, 26 (76.5%) and 8 (23.5%) patients received primary RAUN and RAUN with psoas hitch technique, respectively. Refluxing RAUN method was performed in all cases. No intraoperative complications were found. Two patients had a radiologic and symptomatic recurrence; one was managed with a repeat surgery while the other received ureteral dilatation treatment. Conclusion: Both our study and the published literature showed that RAUN is a safe, less invasive, and effective surgical technique that can easily replicate the open ureteroneocystostomy for managing lower ureteral diseases. Keywords: Outcomes, Psoas hitch, Robot-assisted, Ureteroneocystostomy

Kidney renal clear cell carcinoma (KIRC) has high morbidity and gradually increased in recent years, and the rate of progression once relapsed is high. At present, owing to lack of effective prognosis predicted markers and post-recurrence drug selection guidelines, the prognosis of KIRC patients is greatly affected. Necroptosis is a regulated form of cell necrosis in a way that is independent of caspase. Induced necroptosis is considered an effective strategy in chemotherapy and targeted drugs, and it can also be used to improve the efficacy of immunotherapy. Herein, we quantified the necroptosis landscape of KIRC patients from The Cancer Genome Atlas (TCGA) database and divided them into two distinct necroptosis-related patterns (C1 and C2) through the non-negative matrix factorization (NMF) algorithm. Multi-analysis revealed the differences in clinicopathological characteristics and tumor immune microenvironment (TIME). Then, we constructed the NRG prognosis signature (NRGscore), which contained 10 NRGs (PLK1, APP, TNFRSF21, CXCL8, MYCN, TNFRSF1A, TRAF2, HSP90AA1, STUB1, and FLT3). We confirmed that NRGscore could be used as an independent prognostic marker for KIRC patients and performed excellent stability and accuracy. A nomogram model was also established to provide a more beneficial prognostic indicator for the clinic. We found that NRGscore was significantly correlated with clinicopathological characteristics, TIME, and tumor mutation burden (TMB) of KIRC patients. Moreover, NRGscore had effective guiding significance for immunotherapy, chemotherapy, and targeted drugs.

Background: Thulium laser resection of bladder tumors (TmLRBT) is recently considered as a common treatment option for non-muscle-invasive bladder cancers (NMIBC), but whether it is superior to Transurethral resection of bladder tumors (TURBT) are still undetermined.Materials and Methods: We retrospectively screened our institution database to identify patients who were treated by conventional TURBT or TmLRBT for NMIBC and followed by intravesical bacillus Calmette-Guérin (BCG) immunotherapy. The preoperative characteristics, perioperative outcomes, and recurrence-free survival were compared to assess the safety and efficacy of the two procedures.Results: Eventually, 90 patients who underwent TmLRBT (n = 37) or TURBT (n = 53) followed by intravesical BCG immunotherapy were included. Two groups were similar in baseline characteristics except for the smaller tumor size of the TmLRBT group(1.7 cm vs. 2.2 cm; P = 0.036). Obturator nerve reflex occurred in eight patients in the TURBT group and 3 of them suffered from bladder perforation while none happened in the TmLRBT group. The TmLRBT also had a shorter irrigation duration. In the multivariate Cox regression, the TmLRBT was related to less recurrence risk (HR: 0.268; 95% CI, 0.095–0.759; P = 0.013).Conclusion: Our results suggested that TmLRBT is safer than conventional TURBT with fewer perioperative complications, and it offers better cancer control, therefore might be a superior option for NMIBC patients with intermediate and high recurrence risk.

Recent reports focus on the hydrogenation engineering of monolayer boron phosphide and simultaneously explore its promising applications in nanoelectronics. Coupling density functional theory and finite element method, we investigate the bowtie triangle ring microstructure composed of boron phosphide with hydrogenation based on structural and performance analysis. We determine the carrier mobility of hydrogenated boron phosphide, reveal the effect of structural and material parameters on resonance frequencies, and discuss the variation of the electric field at the two tips. The results suggest that the mobilities of electrons for hydrogenated BP monolayer in the armchair and zigzag directions are 0.51 and 94.4 cm2·V−1·s−1, whereas for holes, the values are 136.8 and 175.15 cm2·V−1·s−1. Meanwhile, the transmission spectra of the bowtie triangle ring microstructure can be controlled by adjusting the length of the bowtie triangle ring microstructure and carrier density of hydrogenated BP. With the increasing length, the transmission spectrum has a red-shift and the electric field at the tips of equilateral triangle rings is significantly weakened. Furthermore, the theoretical sensitivity of the BTR structure reaches 100 GHz/RIU, which is sufficient to determine healthy and COVID-19-infected individuals. Our findings may open up new avenues for promising applications in the rapid diagnosis of COVID-19.

Owing to the outstanding physical properties of graphene, its biosensing applications implemented by the terahertz metasurface are widely concerned and studied. Here, we present a novel design of the graphene metasurface, which consists of an individual graphene ring and an H-shaped graphene structure. The graphene metasurface exhibits a dual-resonance response, whose resonance frequency strongly varies with the geometrical parameters of the proposed metasurface, the carrier density of graphene, and the analyte composition. The transparency window, including width and position, can be artificially controlled by adjusting the geometrical parameters or the Fermi energy. Furthermore, the sensing parameters of the graphene metasurface for cancerous and normal cells are investigated, focusing on two factors, namely cell quantity and position on the metasurface. The simulated results clearly show that the theoretical sensitivity, figure of merit, and quantity of the graphene metasurface for breast cells reach 1.21 THz/RIU, 2.75 RIU−1, and 2.43, respectively. Our findings may open up new avenues for promising applications in the diagnosis of cancers.

Pharmacological therapy of diabetes mellitus-induced erectile dysfunction (DMED) is intractable owig to the poor response to phosphodiesterase type 5 inhibitors (PDE5i). The surge in the number of diabetic patients makes it extremely urgent to find a novel therapy for DMED. Ferroptosis is a recently discovered form of cell death evoked by lipid peroxidation and is related to several diabetic complications. GPX4, an important phospholipid hydroperoxidase, can alleviate ferroptosis and maintain redox balance via reducing lipid peroxides. However, whether GPX4 can be a prospective target of DMED needs to be determined. Fifty rats were randomly divided into control group, DMED group, DMED + negative control group (DMED + NC group), DMED + low-dose group (1 × 106 infectious units), and DMED + high-dose group (2 × 106 infectious units). Erectile function was assessed 4 weeks after intracavernous injection of GPX4 or negative control lentivirus. The penile shafts were collected for subsequent molecular biological and histological analysis. The results demonstrated that erectile function of the rats in DMED and DMED + NC groups was extremely impaired and was improved in a dose-dependent manner with GPX4 lentivirus (GPX4-LV) injection. Additionally, upregulation of the ACSL4-LPCAT3-LOX pathway, iron overload, oxidative stress, fibrosis, and decreased endothelial and smooth muscle cell numbers were observed in the corpus cavernosum of DMED group. Meanwhile, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway was inhibited, and the Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway was promoted in DMED rats. The above histologic alterations and related molecular changes were alleviated after GPX4-LV injection. The results revealed that GPX4 improved erectile function by modulating ferroptosis during DMED progression. This finding is of paramount significance in deciphering the molecular mechanism of hyperglycemia-induced ferroptosis, thereby providing a prospective target for preventing the development of DMED.

Background Proteins are the most abundant component of kidney stone matrices and their presence may reflect the process of the stone’s formation. Many studies have explored the proteomics of urinary stones and crystals. We sought to comprehensively identify the proteins found in kidney stones and to identify new, reliable biomolecules for use in nephrolithiasis research. Methods We conducted bioinformatics research in November 2020 on the proteomics of urinary stones and crystals. We used the ClusterProfiler R package to transform proteins into their corresponding genes and Ensembl IDs. In each study we located where proteomic results intersected to determine the 20 most frequently identified stone matrix proteins. We used the Human Protein Atlas to obtain the biological information of the 20 proteins and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis to explore their biological functions. We also performed immunohistochemistry to detect the expression of the top five stone matrix proteins in renal tissue. Results We included 19 relevant studies for analysis. We then identified 1,409 proteins in the stone matrix after the duplicates were removed. The 20 most-commonly identified stone matrix proteins were: S100A8, S100A9, uromodulin, albumin, osteopontin, lactotransferrin, vitamin K-dependent protein Z, prothrombin, hemoglobin subunit beta, myeloperoxidase, mannan-binding lectin serine protease 2, lysozyme C, complement C3, serum amyloid P-component, cathepsin G, vitronectin, apolipoprotein A-1, eosinophil cationic protein, fibrinogen alpha chain, and apolipoprotein D. GO and KEGG analysis revealed that these proteins were typically engaged in inflammation and immune response.Immunohistochemistry of the top five stone matrix proteins in renal tissue showed that the expression of S100A8, S100A9, and osteopontin increased, while uromodulin decreased in kidney stone patients. Albumin was rarely expressed in the kidney with no significant difference between healthy controls and kidney stone patients. Conclusion Proteomic analysis revealed some common inflammation-related proteins in the kidney stone matrix. The role of these proteins in stone formation should be explored for their potential use as diagnostic biomarkers and therapeutic targets for urolithiasis.

Post-transcriptional regulation plays a leading role in gene regulation and RNA binding proteins (RBPs) are the most important posttranscriptional regulatory protein. RBPs had been found to be abnormally expressed in a variety of tumors and is closely related to its occurrence and progression. However, the exact mechanism of RBPs in bladder cancer (BC) is unknown. We downloaded transcriptomic data of BC from the Cancer Genome Atlas (TCGA) database and used bioinformatics techniques for subsequent analysis. A total of 116 differentially expressed RBPs were selected, among which 61 were up-regulated and 55 were down-regulated. We then identified 12 prognostic RBPs including CTIF, CTU1, DARS2, ENOX1, IGF2BP2, LIN28A, MTG1, NOVA1, PPARGC1B, RBMS3, TDRD1, and ZNF106, and constructed a prognostic risk score model. Based on this model we found that patients in the high-risk group had poorer overall survival (P < 0.001), and the area under the receiver operator characteristic curve for this model was 0.677 for 1 year, 0.697 for 3 years, and 0.709 for 5 years. Next, we drew a nomogram based on the risk score and other clinical variables, which showed better predictive performance. Our findings contribute to a better understanding of the pathogenesis, progression and metastasis of BC. The model of these 12 genes has good predictive value and may have good prospects for improving clinical treatment regimens and patient prognosis.