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

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

A Novel Hydrodynamic Design Greatly Improves the Debris Clearance Rate of Flexible Ureteroscopy.

Objectives: To introduce a novel hydrodynamic design for a flexible ureteroscope that can increase stone debris clearance. Methods: Based on hydrodynamics, the new design allowed the ureteroscope to have six water jets. Fluid gushed from the six jets and would ultimately converge into an eddy. The safety and stone debris clearance efficiency were tested in a 3D-printed kidney model. Stone fragments between 0.5 and 1 mm were used to mimic the debris. A ureteroscope already approved for marketing was used as a control. Results: The new design did not change the local renal pressure and did not raise the whole renal pressure under irrigation at 80 or 100 mL/min but slightly raised it under irrigation at 120 mL/min. The pressures in the 2 g stone clearance procedures were 26.0, 33.1, and 37.5 cmH2O for the new design and 25.1, 30.2, and 39.3 cmH2O for the current design; in the 4 g stone clearance procedures, the pressures were 30.1, 37.2, and 40.0 cmH2O for the new design and 26.9, 30.8, and 39.8 cmH2O for the current design, all under conditions of 80, 100, and 120 mL/min irrigation, respectively. The new design significantly improved the stone clearance rate by ∼10-fold. It effectively cleared 2 and 4 g stones within 900 seconds under the three irrigation rates. In contrast, the current design cleared <10% of the stone debris in all tests. Conclusion: The new hydrodynamic design significantly improved the stone debris clearance rate without causing obviously increased renal pressure, and the improvement was maintained under different irrigation pressures and stone burdens.

Mechanical and Electromagnetic Wave Absorption Performance of Carbonyl Iron Powder-Modified Nonwoven Materials.

In order to develop carbonyl iron-enhanced electromagnetic wave-absorbing composites, this paper utilizes two different morphologies of carbonyl iron powder (CIP), spherical and flake-like, which are blended with aqueous polyurethane (PU) in three different ratios to prepare impregnating solutions. Polyester (PET) needle-punched nonwoven materials are impregnated with these solutions to produce electromagnetic wave-absorbing composites. First, electromagnetic parameters of the two CIP particle types, spherical carbonyl iron (SCIP) and flake-like carbonyl iron (FCIP), are tested with the coaxial method, followed by calculation of the results of their electromagnetic wave absorption performance. Next, the composites are subjected to microscopic morphology observation, tensile testing, and arched frame method electromagnetic wave absorption performance testing. The results indicate that the microwave absorption performance of FCIP is significantly better than that of SCIP. The minimum reflection loss value for F3, a kind of FCIP-modified nonwoven fabric, at the thickness of 1 mm, at 18 GHz is -17 dB. This value is even better than the calculated RL value of CIP at the thickness of 1 mm. The anisotropic shape of flake-like magnetic materials is further strengthened when adhering to the surface of PET fiber material. Additionally, the modified composites with carbonyl iron exhibit higher tensile strength compared with pure PET. The addition of fibrous skeletal materials is expected to enhance the impedance matching of flake-like magnetic particles, forming a wearable and microwave-absorbing composite.

Copy number variations (CNVs) and karyotyping analysis in males with azoospermia and oligospermia.

BACKGROUND: Considering the essential roles that genetic factors play in azoospermia and oligospermia, this study aims to identify abnormal chromosomes using karyotyping and CNVs and elucidate the associated genes in patients. METHODS: A total of 1157 azoospermia and oligospermia patients were recruited, of whom, 769 and 674 underwent next-generation sequencing (NGS) to identify CNVs and routine G-band karyotyping, respectively. RESULTS: First, 286 patients were co-analyzed using CNV sequencing (CNV-seq) and karyotyping. Of the 725 and 432 patients with azoospermia and oligospermia, 33.8% and 48.9% had abnormal karyotypes and CNVs, respectively. In particular, 47,XXY accounted for 44.18% and 26.33% of abnormal karyotypes and CNVs, respectively, representing the most frequent genetic aberration in azoospermia and oligospermia patients. Nevertheless, big Y and small Y accounted for 7.46% and 16.67% of abnormal karyotypes, respectively. We also identified high-frequency CNVs-loci, such as Xp22.31 and 2p24.3, in azoospermia and oligospermia patients. CONCLUSION: Sex chromosome and autosomal CNV loci, such as Xp22.31 and 2p24.3, as well as the associated genes, such as VCX and NACAP9, could be candidate spermatogenesis genes. The high-frequency abnormal karyotypes, CNV loci, and hot genes represent new targets for future research.

Fabrication and Investigation of the Microwave Absorption of Nonwovens Modified by Carbon Nanotubes and Graphene Flakes.

This study aims to investigate the influences of carbon nanotubes (CNTs) and graphene flakes (GFs) on the microwave absorption performance of nonwovens. Nonwovens were modified with CNTs and GFs through an impregnation method, creating a series of absorption samples with different carbon nanomaterial contents. Then the absorption performance of the samples was tested on both sides in the X-band (8.2~12.4 GHz) and the Ku-band (12~18 GHz) using the arch method. The experimental results showed that the absorption performance of GF-impregnated nonwovens was superior to that of CNT-impregnated nonwovens, and the overall absorption performance in the Ku-band was better than in the X-band. At a CNT content of 5 wt.%, the reflection loss of the impregnated nonwovens on the backside reached a minimum of -14.06 dB and remained below -10 dB in the 17.42~17.88 GHz frequency range. The sample fabricated with 4 wt.% GFs in the impregnation solution exhibited the best absorption performance, with minimum reflection losses of -15.33 dB and -33.18 GHz in the X-band and Ku-band, respectively. When the GFs were at 3 wt.%, the absorption bandwidth below -10 dB reached 4.16 GHz. In contrast to CNT-impregnated nonwovens, the frontside of GF-impregnated nonwovens demonstrated better absorption performance in the Ku-band. The results of this work provide experimental data support for the fabrication and application of microwave absorption materials.

Identification of Two Clusters in Renal Pelvis Urobiome of Unilateral Stone Formers Using 2bRAD-M.

Urolithiasis is a common urological disease with increasing incidence and a high recurrence rate, whose etiology is not fully understood. The application of sequencing and culturomics has revealed that urolithiasis is closely related to the urinary microbiome (urobiome), shedding new light on the pathogenesis of stone formation. In this study, we recruited 30 patients with unilateral stones and collected their renal pelvis urine from both sides. Then, we performed 2bRAD-M, a novel sequencing technique that provides precise microbial identification at the species level, to characterize the renal pelvis urobiome of unilateral stone formers in the both sides. We first found that the urobiome in the stone side could be divided into two clusters (Stone1 and Stone2) based on distance algorithms. Stone2 harbored higher microbial richness and diversity compared to Stone1. The genera Cupriavidus and Sphingomonas were overrepresented in Stone1, whereas Acinetobacter and Pseudomonas were overrepresented in Stone2. Meanwhile, differential species were identified between Stone1 and Stone2. We further constructed a random forest model to discriminate two clusters which achieved a powerful diagnostic potential. Moreover, the urobiome of the non-stone side (Control1/2) was compared with that of the stone side (Stone1/2). Stone1 and Control1 showed different microbial community distributions, while Stone2 was similar to Control2 based on diversity analysis. We also identified differentially abundant species among all groups. We assumed that there might be different mechanisms of how microbiota contribute to stone formation in two clusters. Our findings might assist in the selection of suitable medical treatments for urolithiasis.

The role of microbiome: a novel insight into urolithiasis.

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

A Systematic Review on the Role of Repeat Transurethral Resection after Initial en Bloc Resection for Non-Muscle Invasive Bladder Cancer.

International guidelines recommend repeat transurethral resection of bladder tumors (reTURB) for selected patients with high-risk non-muscle invasive bladder cancer to remove possible residual tumors, restage tumors and improve the therapeutic outcome. However, most evidence supporting the benefits of reTURB is from conventional TURB. The role of reTURB in patients receiving initial En bloc resection of bladder tumor (ERBT) is still unknown. PubMed, Embase, Web of Science, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were systematically searched. Finally, this systematic review and meta-analysis included twelve articles, including 539 patients. The rates of residual tumor and tumor upstaging detected by reTURB after ERBT were 5.9% (95%CI, 2.0%-11.1%) and 0.0% (95%CI, 0.0%-0.5%), respectively. Recurrence-free survival, tumor recurrence and progression were comparable between patients with and without reTURB after initial ERBT. The pooled hazard ratios of 1-year, 2-year, 3-year and 5-year recurrence-free survival were 0.74 (95%CI, 0.36-1.51; p = 0.40), 0.76 (95%CI, 0.45-1.26; p = 0.28), 0.83 (95%CI, 0.53-1.32; p = 0.43) and 0.83 (95%CI, 0.56-1.23; p = 0.36), respectively. The pooled relative risks of recurrence and progression were 0.87 (95%CI, 0.64-1.20; p = 0.40) and 1.11 (95%CI, 0.54-2.32; p = 0.77), respectively. Current evidence demonstrates that reTURB after ERBT for bladder cancer can detect relatively low rates of residual tumor and tumor upstaging and appears not to improve either recurrence or progression.

A simple predictive model with internal validation for assessment of stone-left after ureteroscopic lithotripsy in upper ureteral stones.

Background: Stone free rate in upper ureteral stones is not as high. We sought to identify easily accessible risk factors attributing to stones left in the ureteroscopy in the treatment of upper ureteral calculi, and to build a simple and reliable predictive model. Methods: Patients treating only for upper ureteral stones in 2018 were retrospectively analyzed. Correlations between factors and the stone free rate were analyzed using bidirectional stepwise regression, curve fitting and binary logistic regression. Stone shape was judged by the gap between length and width in the two-dimensional section. A predictive nomogram model was built based on those selected variables (P<0.05). The area under the receiver operator characteristic curve (AUC) and calibration curve were used to access its discrimination and calibration. Decision curve analysis (DCA) was conducted to test the clinical usefulness. Results: Totally, 275 patients with 284 stones were enrolled in this research. Bidirectional stepwise regression showed that stone length had a significant effect on stone free, instead of width or burden. Stone shapes were also found playing a big role. Curve fitting showed that quasi-circular stones had a high risk of retropulsion, and eventually led to stone left. Finally, stone length, shape, modality, and the distance of stones to the ureteropelvic junction were enrolled in the model. Among them, the distance of the stone to the ureteropelvic junction showed a noticeable impact on stone left. AUC was 0.803 (95% CI: 0.730-0.876), and the calibration curve showed good calibration of the model (concordance index, 0.792). DCA indicated the model added net benefit to patients. Conclusions: The present predictive model based on those factors, stones length, shape, modality, and distance of the stone to the ureteropelvic junction was easy, reliable and useful.

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

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

Epidemiological Trends of Urolithiasis at the Global, Regional, and National Levels: A Population-Based Study.

Background: Urolithiasis is common worldwide and can predispose to urinary tract infections and renal failure. We aimed to explore the global, regional, and national burden of urolithiasis between 1990 and 2019, stratified by sex, age, and sociodemographic index (SDI). Methods: From 1990 to 2019, data on the number of incident cases of urolithiasis, associated deaths, and disability-adjusted life years (DALYs) were extracted from the 2019 Global Burden of Disease (GBD) study. The trends for the incidence rate, mortality, and DALYs were evaluated using estimated annual percentage changes (EAPCs). Results: The incidence of urolithiasis increased by 48.57%, from 77.78 million incident cases in 1990 to 115.55 million in 2019, while its age-standardized incidence rate (ASIR) decreased. The ASIR increased slightly in the low SDI regions (EAPC = 0.33; 95% confidence interval [CI]: 0.24-0.43), while ASIRs in other SDI regions decreased. The incidence of urolithiasis by age presented a unimodal distribution, with the peak observed in patients aged between 50 years and 70 years. Urolithiasis-related mortality and DALYs also increased over time. Yet, the age-standardized death rate (ASDR) decreased by 2.05% (95% CI, -2.25% to -1.85%) per year, and the annual age-standardized DALY rate decreased by 1.77% (95% CI, -1.92% to -1.63%). The mortality and DALYs increased with age. The incidence, mortality, and DALYs were greater in males than those in females. The burden of urolithiasis showed obvious differences in its regional distribution over the past three decades. Conclusion: From 1990 to 2019, ASIR, ASDR, and age-standardized DALY rate of urolithiasis have decreased. Yet, particularly significant differences exist in the geographic, age, and sex distribution. Thus, medical resources should be rationally allocated and adjusted according to the geographic and demographic distribution of urolithiasis.

Application of Suctioning Ureteral Access Sheath during Flexible Ureteroscopy for Renal Stones Decreases the Risk of Postoperative Systemic Inflammatory Response Syndrome.

Purpose: To clarify the efficiency and outcomes of suctioning ureteral access sheath (UAS) during flexible ureteroscopic lithotripsy (fURL) for the management of renal stones. Methods: Between January 2017 and January 2019, a total of 444 patients with renal stones undergoing fURL were divided into suctioning UAS and nonsuctioning UAS groups. The outcomes of patients in both groups were compared using a matched-pair analysis (1 : 1 scenario). Furthermore, a directed acyclic graph (DAG) was drawn to guide the multivariate logistic regression model and analyze the protective effect of suctioning UAS on the incidence of postoperative systemic inflammatory response syndrome (SIRS). Results: Before propensity score matching, significant differences were observed between the two groups in blood white cell counts, urine white cell counts, preoperative fever, preoperative indwelling stents, and laterality (P < 0.05). Eighty-one patients in the suctioning UAS group were successfully matched with 81 patients in the nonsuctioning group. The stone-free rate (SFR) on postoperative day 1 after fURL in the suctioning group was higher than that in the nonsuctioning group (86.4% vs. 71.6%; P=0.034), whereas it was comparable between the two groups 1 month after the surgery (88.9% vs. 82.7%; P=0.368). The incidence of postoperative fever or SIRS was lower in the suctioning group (fever: 3.70% vs. 14.8%; P=0.030; SIRS: 1.23% vs. 12.3%; P=0.012). However, the operative duration was similar in both groups (mean (SD)) (72.9 (28.1) min vs. 80.0 (29.5) min; P=0.121). The result of the multivariate logistic regression model guided by DAG revealed that the application of nonsuctioning UAS (odds ratio: 5.28 [1.38-35.07], P=0.034) during fURL was associated with postoperative SIRS. Conclusions: The application of suctioning UAS during fURL was associated with higher SFR on day 1 after surgery and a lower incidence of postoperative fever or SIRS.

Impact of Treatment Modalities on Prognosis in Patients With Renal Collecting Duct Carcinoma: A Population-Based Study.

Objective: Renal 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. Methods: Patients' 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. Results: A 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. Conclusions: CDC 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.

Cost-effectiveness of anti-retropulsive devices varies according to the locations of proximal ureteral stones: a retrospective cohort study.

BACKGROUND: Anti-retropulsive devices are often used to prevent stone migration in the treatment of proximal ureteral calculi. They are helpful. However, in the meantime, they also add extra expenses. This study was carried out to investigate the best criteria for treating proximal ureteral stones with anti-retropulsive devices. METHODS: Data from all patients who underwent ureteroscopic holmium: YAG laser lithotripsy for solitary upper ureteral stones in 2018 were collected. Patients who encountered stone retropulsion during the process of inserting the ureteroscope were excluded. Patients were divided into either group URS or group URS + ARD depending on whether the anti-retropulsive device was used. Then, the stone-free rate, expenses and other criteria were compared between groups according to stone location. Stone-free was defined as no stones present. RESULTS: For stones located ≤ 30 mm from the ureteropelvic junction (UPJ), the stone-free rates for the URS group were 80% and 80% at one day and one month after the operation, respectively. Those for the URS + ARD group were 71.4% and 78.6% at one day and one month, respectively. For stones located 31-90 mm from the UPJ, the stone-free rates were 84.7% and 84.7% for the URS group and 89.6% and 95.5% for the URS + ARD group at one day and one month, respectively. A statistically significant difference occurred at one month. For stones located > 90 mm from the UPJ, the two groups were both stone free. In the URS + ARD group, expenses were higher. In addition, the mean diameter of residual stones derived from stones located at 31-90 mm from the UPJ was statistically smaller, and 4 of 7 residual stones passed spontaneously within one month, which was obviously more than that in other locations and the URS group. Other outcomes, including operation time and postoperative stay, showed no significant difference between the groups. CONCLUSION: Anti-retropulsive devices are indeed helpful, but they might be cost-effective for stones located solely in the middle part of the upper ureter, not for those too close to or far from the ureteropelvic junction.

The role of reactive oxygen species derived from different NADPH oxidase isoforms and mitochondria in oxalate-induced oxidative stress and cell injury.

Hyperoxaluria is a risk factor for urolithiasis and can cause renal epithelial cell injury secondary to oxidative stress. Reactive oxygen species (ROS) produced during cell damage originate from different sources and play different roles. Here, we explored the potential sources of ROS production and investigated the role of ROS from various sources in oxalate-induced oxidative stress and cell injury in normal rat kidney-52 epithelial (NRK-52E) cells. Oxalate-induced injury was assessed by lactate dehydrogenase (LDH) release experiments. 2,7-dichlorodihydrofluorescein diacetate and mitoSOX Red were used to determine the intracellular and mitochondrial ROS (mtROS) production, respectively. The expression level of Nox4, Nox2, and p22 protein was detected by Western blotting to observe the effect of oxalate on nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase (Nox). Furthermore, a specific NADPH oxidase subtype inhibitor and targeted mitochondrial antioxidants were used to preliminarily identify the role of ROS from different sources in renal tubular epithelial cell injury induced by oxalate. We found that oxalate inhibited cell viability, induced LDH release, and prompted intracellular and mitochondrial ROS (mtROS) production. Oxalate also decreased the protein expression level of Nox4 and increased the protein expression level of p22. Mitochondria were also a source of ROS production. In addition, Nox2 inhibitor or mtROS scavenging prevented oxalate-induced cell injury, reversed by an inhibitor of Nox4/1. We concluded that ROS from different sources might play different roles in oxalate-induced renal tubular epithelial cell injury. We also identified new potential targets for preventing or alleviating oxalate-induced renal tubular epithelial cell injury.

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.

Analysis of Preoperative Risk Factors for Postoperative Urosepsis After Mini-Percutaneous Nephrolithotomy in Patients with Large Kidney Stones.

Purpose: To assess the preoperative risk factors for postoperative urosepsis after mini-percutaneous nephrolithotomy (mPCNL) in patients with large kidney stones. Methods: Records of 171 patients with large (≥30 mm) kidney stones who underwent mPCNL from December 2013 to October 2019 were reviewed. Demographic data of patients, preoperative urine analysis, urine culture, and routine blood tests and abdominal computerized cosmography data were collected and analyzed. A predictive nomogram model was established based on the results of logistic regression. Results: Twenty-nine patients (17%) developed postoperative urosepsis in this study. Univariate analysis demonstrated that preoperative urine leukocytes (p < 0.001), urine nitrite (p < 0.001), stones in adjacent calices on the coronal plane (p < 0.001), the maximum cross-sectional area of stones (p < 0.001), the diameter of hydronephrosis (p = 0.010), and number of stones (p = 0.044) were associated with postoperative urosepsis after mPCNL in patients with large kidney stones. And preoperative urine leukocytes ≥450/µL (p = 0.002) was the only independent risk factor for postoperative urosepsis in multivariate logistic regression analysis. Based on the results of multivariate regression, a nomogram model was established for the prediction of postoperative urosepsis with ideal discrimination (area under receiver operating characteristic curve was 0.867). Conclusion: Patients with certain preoperative characteristics, including higher urine leukocytes, positive urine nitrite, stones in adjacent calices on the coronal plane, larger maximum cross-sectional area of stones, larger diameter of hydronephrosis, and larger number of stones, who received mPCNL may have a higher risk of postoperative urosepsis. A predictive model can help urologists identify patients who may develop postoperative urosepsis with high probability.

Lung detection and severity prediction of pneumonia patients based on COVID-19 DET-PRE network.

BACKGROUND: The sudden outbreak of COVID-19 pneumonia has brought a heavy disaster to individuals globally. Facing this new virus, the clinicians have no automatic tools to assess the severity of pneumonia patients. METHODS: In the current work, a COVID-19 DET-PRE network with two pipelines was proposed. Firstly, the lungs in X-rays were detected and segmented through the improved YOLOv3 Dense network to remove redundant features. Then, the VGG16 classifier was pre-trained on the source domain, and the severity of the disease was predicted on the target domain by means of transfer learning. RESULTS: The experiment results demonstrated that the COVID-19 DET-PRE network can effectively detect the lungs from X-rays and accurately predict the severity of the disease. The mean average precisions (mAPs) of lung detection in patients with mild and severe illness were 0.976 and 0.983 respectively. Moreover, the accuracy of severity prediction of COVID-19 pneumonia can reach 86.1%. CONCLUSIONS: The proposed neural network has high accuracy, which is suitable for the clinical diagnosis of COVID-19 pneumonia.

Clinicopathological Features and Prognostic Outcomes of Papillary Renal Cell Carcinoma.

PURPOSE: Although papillary renal cell carcinoma (pRCC) is the second common renal malignant tumor, the current understanding of pRCC is poor. This study aims to explore the clinicopathological features and prognostic factors of pRCC. METHODS: From August 2007 and August 2017, 87 patients diagnosed with pRCC by postoperative pathology were enrolled. The clinicopathological features between type1 pRCC and type2 pRCC were compared by Chi-square test, Fisher's exact test, or t-test. The Kaplan-Meier method was performed to estimate progression-free survival (PFS). Univariate and multivariate cox regression models were used to verify the prognostic factors. RESULTS: Of the 87 cases, the median tumor diameter was 5.3cm. Twenty-nine patients were diagnosed with type1 pRCC and 58 patients with type2 pRCC. According pathological stage, 59 (67.8%) cases were in pT1 stage, 19 (21.8%) in pT2 stage, and 9 (10.4%) in pT3 stage. WHO/ISUP pathological grade revealed that 56 (64.4%) patients were in grade I, 17 (19.5%) in grade II, 7 (8.05%) in grade III, and 7 (8.05%) in grade IV. The median follow-up time was 57.0months, and the 1-, 3-year PFS was 95.4%, and 80.8%, respectively. For type1 and type2 pRCC, 3-years PFS was 93.0% and 74.9%, respectively. Survival of type1 pRCC was better than that of type2 (P= 0.027). Patients with late pT stage, lymph node metastasis, distant metastasis, high pathological grade, and large size exhibited worse survival. pTNM stage, pathological grade, and tumor types were potentially related to prognosis for PFS. However, an independent prognostic factor affecting PFS was not found in multivariate regression models. For patients with the pT1 stage, nephron-sparing surgery (NSS) and radical nephrectomy (RN) did not affect the PFS, ignoring tumor types (P=0.45). CONCLUSION: Type2 pRCC is more than type1 pRCC and has an advanced TNM stage and a higher pathological grade. For patients with pRCC with the pT1 stage, the outcome of NSS is not inferior to that of RN.

Proteomic analysis reveals some common proteins in the kidney stone matrix.

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.