Exosome, the glass slipper for Cinderella of cancer-bladder cancer?

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.

Reduction of Ice Adhesion Using Surface Acoustic Waves: Nanoscale Vibration and Interface Heating Effects.

Ice accumulation causes great risks to aircraft, electric power lines, and wind-turbine blades. For the ice accumulation on structural surfaces, ice adhesion force is a crucial factor, which generally has two main sources, for exampple, electrostatic force and mechanical interlocking. Herein, we present that surface acoustic waves (SAWs) can be applied to minimize ice adhesion by simultaneously reducing electrostatic force and mechanical interlocking, and generating interface heating effect. A theoretical model of ice adhesion considering the effect of SAWs is first established. Experimental studies proved that the combination of nanoscale vibration and interface heating effects lead to the reduction of ice adhesion on the substrate. With the increase of SAW power, the electrostatic force decreases due to the increase of dipole spacings, which is mainly attributed to the SAW induced nanoscale surface vibration. The interface heating effect leads to the transition of the locally interfacial contact phase from solid-solid to solid-liquid, hence reducing the mechanical interlocking of ice. This study presents a strategy of using SAWs device for ice adhesion reduction, and results show a considerable potential for application in deicing.

Secondary Management for Recurrent Ureteropelvic Junction Obstruction after Pyeloplasty: A Comparison of Re-Do Robot-Assisted Laparoscopic Pyeloplasty and Conventional Laparoscopic Pyeloplasty.

OBJECTIVE: To describe and analyze our experience with secondary robot-assisted laparoscopic pyeloplasty (RALP) and conventional laparoscopic pyeloplasty (LP) in treating recurrent ureteropelvic junction obstruction (UPJO) after primary pyeloplasty. METHODS: Patients who underwent secondary RALP or LP for recurrent UPJO were retrospectively analyzed. Baseline characteristics, detailed history of previous pyeloplasty, operative profile and follow-up data were collected and analyzed. RESULTS: Among 29 patients presented with recurrent UPJO, 15 patients underwent secondary RALP. Both groups (RALP or LP) were comparable in baseline characteristics and detailed history of previous pyeloplasty. The mean operative time, suturing time, and hospitalization time of patients in RALP group were significantly less than those in LP group. The mean operative time of RALP group was 2.1 h, while the mean operative time of LP group was 3.23 h. The average suturing time of LP (62.43 min) is about 3 times that of RALP (21.47 min). The overall mean follow-up data was 23 months. The success rate of the RALP group and LP group was 87.7 and 85.7% respectively. CONCLUSION: Compared to LP, RALP may be a better choice for the treatment of recurrent UPJO. Further high-quality clinical studies are needed to confirm the superior nature of RALP.

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.

Regioselective Benzoylation of Diols and Carbohydrates by Catalytic Amounts of Organobase.

A novel metal-free organobase-catalyzed regioselective benzoylation of diols and carbohydrates has been developed. Treatment of diol and carbohydrate substrates with 1.1 equiv. of 1-benzoylimidazole and 0.2 equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in MeCN under mild conditions resulted in highly regioselective benzoylation for the primary hydroxyl group. Importantly, compared to most commonly used protecting bulky groups for primary hydroxyl groups, the benzoyl protective group offers a new protection strategy.

The Wnt11 Signaling Pathway in Potential Cellular EMT and Osteochondral Differentiation Progression in Nephrolithiasis Formation.

The molecular events leading to nephrolithiasis are extremely complex. Previous studies demonstrated that calcium and transforming growth factor-ß1 (TGF-ß1) may participate in the pathogenesis of stone formation, but the explicit mechanism has not been defined. Using a self-created genetic hypercalciuric stone-forming (GHS) rat model, we observed that the increased level of serous/uric TGF-ß1 and elevated intracellular calcium in primary renal tubular epithelial cells (PRECs) was associated with nephrolithiasis progression in vivo. In the setting of high calcium plus high TGF-ß1 in vitro, PRECs showed great potential epithelial to mesenchymal transition (EMT) progression and osteochondral differentiation properties, representing the multifarious increased mesenchymal and osteochondral phenotypes (Zeb1, Snail1, Col2A1, OPN, Sox9, Runx2) and decreased epithelial phenotypes (E-cadherin, CK19) bythe detection of mRNAs and corresponding proteins. Moreover, TGF-ß-dependent Wnt11 knockdown and L-type Ca2+ channel blocker could greatly reverse EMT progression and osteochondral differentiation in PRECs. TGF-ß1 alone could effectively promote EMT, but it had no effect on osteochondral differentiation in NRK cells (Rat kidney epithelial cell line). Stimulation with Ca2+ alone did not accelerate differentiation of NRK. Co-incubation of extracellular Ca2+ and TGF-ß1 synergistically promotes EMT and osteochondral differentiation in NRK control cells. Our data supplied a novel view that the pathogenesis of calcium stone development may be associated with synergic effects of TGF-ß1 and Ca2+, which promote EMT and osteochondral differentiation via Wnt11 and the L-type calcium channel.

Association between genetic variants of the VEGFR-2 gene and the risk of developing endometriosis in Northern Chinese Women.

AIM: To investigate the association of tag single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor receptor 2 (VEGFR-2) gene with susceptibility to endometriosis. METHODS: This study comprised 571 patients with endometriosis and 580 women in the control group. Five tag SNPs in the VEGFR-2 gene were selected using a Haploview program, and those SNPs were genotyped by a method of polymerase chain reaction and ligase detection reaction. RESULTS: Statistical results show that there was a significant difference in the genotype and allele distribution of the 1192C/T polymorphism between the disease group and the control group (p = 0.041 and 0.017). The women carrying the T allele (C/T+T/T genotype) had a lower risk of developing endometriosis compared with the women with the C/C genotype (OR 0.75, 95% CI 0.57-0.99). There was no significant difference in the allele and genotype distribution of four other tag SNPs (1719T/A, +31C/T, IVS25-92A/G and IVS6+​54C/T) between the disease group and the control group (all p > 0.05). CONCLUSIONS: Our results suggested that the 1192C/T polymorphisms on the VEGFR-2 gene might affect the risk of developing endometriosis in Northern Chinese women of Han ethnicity.

The genetics of urinary microbiome, an exploration of the trigger in calcium oxalate stone.

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.

Novel androgen receptor inhibitors for metastatic hormone-sensitive prostate cancer: Current application and future perspectives.

Androgen receptor (AR) signaling is essential in prostate cancer treatment. For many years, androgen deprivation therapy (ADT) has been primarily applied to manage advanced prostate cancer. However, most individuals with metastatic hormone-sensitive prostate cancer (mHSPC) administered ADT alone are at risk of developing metastatic castration-resistant prostate cancer (mCRPC) in less than two years. New approaches employing novel AR inhibitors (ARi) as intensified upfront systemic treatment in mHSPC have recently demonstrated substantial benefits in delaying disease progression and prolonging overall survival. Administration of novel ARi has become the new standard of care in mHSPC. The new landscape simultaneously makes treatment choice more challenging. This review provides comprehensive data on molecular structure, pharmaceutical properties, and efficacy and safety profiles reported by pivotal clinical trials. We also discuss future directions with ongoing Phase III trials of novel ARi in mHSPC. Considering these biological and clinical insights, this review aimed to provide a comprehensive understanding of differences in the development and applications of novel ARi for mHSPC, which may be helpful in designing strategies for first-line treatment choices.

Fundamentals of Monitoring Condensation and Frost/Ice Formation in Cold Environments Using Thin-Film Surface-Acoustic-Wave Technology.

Moisture condensation, fogging, and frost or ice formation on structural surfaces cause severe hazards in many industrial components such as aircraft wings, electric power lines, and wind-turbine blades. Surface-acoustic-wave (SAW) technology, which is based on generating and monitoring acoustic waves propagating along structural surfaces, is one of the most promising techniques for monitoring, predicting, and also eliminating these hazards occurring on these surfaces in a cold environment. Monitoring condensation and frost/ice formation using SAW devices is challenging in practical scenarios including sleet, snow, cold rain, strong wind, and low pressure, and such a detection in various ambient conditions can be complex and requires consideration of various key influencing factors. Herein, the influences of various individual factors such as temperature, humidity, and water vapor pressure, as well as combined or multienvironmental dynamic factors, are investigated, all of which lead to either adsorption of water molecules, condensation, and/or frost/ice in a cold environment on the SAW devices. The influences of these parameters on the frequency shifts of the resonant SAW devices are systematically analyzed. Complemented with experimental studies and data from the literature, relationships among the frequency shifts and changes of temperature and other key factors influencing the dynamic phase transitions of water vapor on SAW devices are investigated to provide important guidance for icing detection and monitoring.

A dynamic reversible phenylboronic acid sensor for real-time determination of protein-carbohydrate interactions on living cancer cells.

Real-time detection of glycosylation on label-free cancer cell surfaces is of significance for the diagnosis and treatment of cancer. In this work, we have successfully developed a novel dynamic reversible sensor based on pH-sensitive phenylboronic esters to determine in real-time the binding kinetics of protein-carbohydrate interactions on suspension cancer cell surfaces using a quartz crystal microbalance (QCM) technique.

CAV1 alleviated CaOx stones formation via suppressing autophagy-dependent ferroptosis.

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/ß-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/ß-Catenin axis, and finally alleviate CaOx stone formation.

Cancer stem/progenitor signatures refine the classification of clear cell renal cell carcinoma with stratified prognosis and decreased immunotherapy efficacy.

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.

Role of Nox4 in High Calcium-Induced Renal Oxidative Stress Damage and Crystal Deposition.

Aims: We aimed at exploring the role of nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (Nox4) in the regulation of hypercalciuria-induced renal oxidative damage and crystal depositions. Results: High calcium activated Nox4 expression through protein kinase C (PKC). Downregulation of Nox4 expression attenuated hypercalciuria-induced osteoblast-associated protein expression, oxidative stress injury, and crystal deposition in rat kidneys of 1,25-dihydroxyvitamin D3 (VitD) urolithiasis model. Further, calcium-induced activation of mitogen-activated protein kinase (MAPK), overexpression of osteoblast-associated protein, oxidative stress injury, apoptosis, and calcium salt deposition in normal rat kidney epithelial-like (NRK-52E) cells were reversed by downregulating Nox4 expression but were enhanced by upregulating Nox4 expression in vitro. Moreover, calcium-induced increases of osteoblast-associated protein expression were attenuated by the c-Jun-N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) inhibitors. Innovation: Our results demonstrated the effect of Nox4 in the pathological process of kidney stones in in vitro and in vivo studies for the first time. Calcium aggravates renal oxidative stress injury and crystal deposition by activating the Nox4-related reactive oxygen species (ROS)-ERK/JNK pathway in the rat kidney. This study is expected to provide a new theoretical basis for the prevention and treatment of kidney stones. Conclusion: Nox4-derived ROS induced by calcium through PKC caused oxidative stress damage and apoptosis in renal tubular epithelial cells; in addition, Nox4-derived ROS induced by calcium mediated abnormal activation of the bone morphogenetic protein 2 (BMP2) signaling pathway through the MAPK signaling pathway, which induced renal tubular epithelial cells to transdifferentiate into osteoblast-like cells, resulting in the formation of a kidney stone. Antioxid. Redox Signal. 36, 15-38.

Comprehensive Analysis of Senescence Characteristics Defines a Novel Prognostic Signature to Guide Personalized Treatment for Clear Cell Renal Cell Carcinoma.

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.

Identification of a Twelve Epithelial-Mesenchymal Transition-Related lncRNA Prognostic Signature in Kidney Clear Cell Carcinoma.

Background: Epithelial-mesenchymal transition (EMT) plays a vital role in tumor metastasis and drug resistance. It has been reported that EMT is regulated by several long noncoding RNAs (lncRNAs). We aimed to identify EMT-related lncRNAs and develop an EMT-related lncRNA prognostic signature in kidney renal clear cell carcinoma (KIRC). Materials and Methods: In total, 530 ccRCC patients with 611 transcriptome profiles were included in this study. We first identified differentially expressed EMT-related lncRNAs. Then, all the samples with transcriptional data and clinical survival information were randomly split into training/test sets at a ratio of 1 : 1. Accordingly, we further developed a twelve differentially expressed EMT-related lncRNA prognostic signature in the training set. Following this, risk analysis, survival analysis, subgroup analysis, and the construction of the ROC curves were applied to verify the efficacy of the signature in the training set, test set, and all patients. Besides, we further investigated the differential immune infiltration, immune checkpoint expression, and immune-related functions between high-risk patients. Finally, we explored the different drug responses to targeted therapy (sunitinib and sorafenib) and immunotherapy (anti-PD1 and anti-CTLA4). Results: A twelve differentially expressed EMT-related lncRNA prognostic signature performed superior in predicting the overall survival of KIRC patients. High-risk patients were observed with a significantly higher immune checkpoint expression and showed better responses to the targeted therapy and immunotherapy. Conclusions: Our study demonstrates that the twelve differentially expressed EMT-related lncRNA prognostic signature could act as an efficient prognostic indicator for KIRC, which also contributes to the decision-making of the further treatment.

Identification and Quantification of Necroptosis Landscape on Therapy and Prognosis in Kidney Renal Clear Cell Carcinoma.

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.

Ureteroscopic lithotripsy combined with paravertebral block anesthesia or general anesthesia: A propensity matched case-control study.

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 < 0.001) episodes in PVB group. There were no significant differences in operative time (p = 0.702), initial stone-free rate (p = 0.686), and total stone-free rate (p = 0.794) between the two groups. The PVB group had lower postoperative pain and prolonged analgesia (p = 0.007). The postoperative hospital stay in the PVB group was significantly shorter (3.20 ± 0.73 vs 3.84 ± 1.32 d, p = 0.001). And the cost of anesthesia was lower in the PVB group (195.47 ± 13.01 vs 396.31 ± 36.45 US dollars, p < 0.001). CONCLUSION: Under PVB anesthesia, URS can be successfully completed without anesthetic transformation, and its efficacy and safety have been demonstrated. When economic aspects are taken into consideration, PVB seems to be a more economical and effective anesthetic method of URS.

The Activation of ROS/NF-κB/MMP-9 Pathway Promotes Calcium-Induced Kidney Crystal Deposition.

Idiopathic hypercalciuria is an important risk factor for the formation of calcium-containing kidney stones. Matrix metalloproteinase-9 (MMP-9) is closely related to cell and tissue remodeling and is involved in ectopic tissue calcification. However, little is known about its role in kidney stone formation. In this study, we found that the expression of MMP-9 and that of osteoblastic-related proteins was increased in normal rat kidney epithelial-like (NRK-52E) cells following treatment with a high concentration of calcium, while the knockout or overexpression of MMP-9 could, respectively, significantly inhibit or upregulate the expression of osteoblastic-related proteins and calcium crystal deposition. In addition, apoptosis and calcium crystal deposition were significantly reduced in Sprague-Dawley rats with 1,25(OH)2D3-induced hypercalciuria following MMP-9 inhibitor I treatment. Furthermore, inhibiting reactive oxygen species (ROS) production or the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway significantly reduced calcium-induced MMP-9 expression and calcium crystal deposition. In summary, our results suggested that a high calcium concentration promotes epithelial-osteoblastic transformation and calcium crystal deposition in renal tubule cells by regulating the ROS/NF-κB/MMP-9 axis and identified a novel role for MMP-9 in regulating calcium-induced calcium crystal deposition in renal tubules.

Ubiquitin Modification Patterns of Clear Cell Renal Cell Carcinoma and the Ubiquitin Score to Aid Immunotherapy and Targeted Therapy.

Ubiquitin modification is the most common protein post-translational modification (PTM) process in organisms, and 1332 ubiquitin regulators have been identified in humans. Ubiquitin regulators, especially E3 ligases and deubiquitinases, are widely involved in immune processes. This study aims to explore the ubiquitin modification features of clear cell renal cell carcinoma (ccRCC) and to elucidate the role of such ubiquitin modifications in shaping anti-tumor immunity and individual benefits from immune checkpoint blockade (ICB). A comprehensive analysis was performed in the TCGA cohort (n = 530) and GEO cohort (n = 682). RNA sequencing data of 758 differentially expressed regulators, which was validated by the proteomics data, was used for k-means unsupervised consensus clustering and three ubiquitin patterns of ccRCC were identified. Then, we focused on the ubiquitin modification and tumor progression signatures, immune infiltration characteristics, and prognostic value. The three patterns with different ubiquitin modification signatures correspond to "immune desert phenotype," "immune resistance phenotype," and "immune-inflammatory phenotype," respectively. To facilitate clinical application, we constructed a ubiquitin score to evaluate individual patients' ubiquitination outcome, and it was demonstrated to be an independent risk factor for overall survival (OS) in multivariate Cox analysis. It was found that the high score group was correlated to higher immune cells infiltrating level and PD-1/PD-L1/CTLA-4 expression. More importantly, we found that the high score group was predicted to be sensitive to anti-PD-1 treatment, while the low-score group showed lower predicted IC50 values in treatment with Pazopanib and Axitinib. In summary, this study elucidated the potential link between ubiquitin modification and immune infiltration landscape of ccRCC for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced ccRCC.