Predictive model of systemic inflammatory response syndrome after percutaneous nephrolithotomy for kidney calculi based on logistic regression.

OBJECTIVE: To establish a predictive model of systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL) for kidney calculi based on logistic regression. METHODS: The data of 148 patients with unilateral kidney calculi treated in Xi'an International Medical Center Hospital from October 2019 to September 2022 were analyzed retrospectively. According to development of SIRS after PCNL, the patients were divided into one group with SIRS after operation (occurrence group, n = 19) and another group without SIRS after operation (non-occurrence group, n = 129). The clinical data of patients were collected, and risk factors for SIRS after PCNL in patients with unilateral kidney calculi were analyzed by logistic regression. RESULTS: Gender, body mass index (BMI), hypertension, diabetes mellitus (DM), calculi size ≥ 30 mm, renal insufficiency, and hydronephrosis were risk factors for postoperative SIRS (P < 0.05). According to multivariate logistic regression analysis, BMI, DM, hypertension, calculi size ≥ 30 mm, and hydronephrosis were independent risk factors for SIRS (P < 0.05). Based on the regression coefficient, a predictive model was established. The occurrence group had a higher risk score than the non-occurrence group (P < 0.05). According to receiver operating characteristic (ROC) curve-based analysis, the area under the curve of risk score for predicting SIRS in patients was 0.898. CONCLUSION: Patients with BMI ≥ 25 kg/m2, DM, hypertension, calculi ≥ 30 mm, and/or hydronephrosis are more likely to suffer SIRS after PCNL. The risk score has high clinical value in the prediction of SIRS.

LncRNA MEG3 alleviates interstitial cystitis in rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.

PURPOSE: Interstitial cystitis (IC), a chronic pain syndrome characterized by urinary frequency, urgency, and bladder or pelvic floor pain, severely affects the quality of life of patients. The aim of this study was to investigate the role and mechanism of long noncoding RNA Maternally Expressed Gene3 (lncRNA MEG3) in IC. METHODS: An IC rat model was established by intraperitoneal injection of cyclophosphamide combined with bladder perfusion of fisetin and tumor necrosis factor-α (TNF-α) to mimic IC. An in vitro model was established using TNF-α-induced rat bladder epithelium cells. H&E staining was used to assess bladder tissue damage and ELISA was used to measure inflammatory cytokine levels. Western blot analysis was used to examine Nrf2, Bax, Bcl-2, cleaved caspase-3, p-p38, p38, p-NF-κB and NF-κB protein expression levels. RNA immunoprecipitation and RNA pull-down assays were used to examine the interaction between MEG3 and Nrf2. RESULTS: MEG3 levels were upregulated in IC tissues and bladder epithelial cells, whereas Nrf2 expression was found to be downregulated. Knockdown of MEG3 reduced bladder tissue injury, inflammation, oxidative stress and apoptosis. MEG3 was negatively correlated with Nrf2. Downregulation of MEG3 alleviated IC inflammation and injury by upregulating Nrf2 and inhibiting the p38/NF-κB pathway. CONCLUSION: Downregulation of MEG3 alleviated inflammation and injury in IC rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.

Circular RNA_0000326 promotes bladder cancer progression via microRNA-338-3p/ETS Proto-Oncogene 1/phosphoinositide-3 kinase/Akt pathway.

Circular RNAs (circRNAs) play a pivotal regulatory role in bladder cancer (BC) occurrence and progression. The expression level, role and mechanism of circ_0000326 in BC remain unknown. In the present study, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to evaluate the expressions of circ_0000326, microRNA-338-3p (miR-338-3p) and ETS Proto-Oncogene 1(ETS1) mRNA in BC tissues and cell lines. Cell counting kit-8 (CCK-8) assay, wound healing assay and flow cytometry were used to detect the impacts of circ_0000326 on BC cell growth, migration and apoptosis. Western blot was used to detect the expressions of ETS1, phospho-phosphoinositide-3 kinase (p-PI3K), phospho-AKT, PI3K and AKT protein. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to analyze the biological function of ETS1 in BC. Here, we found that circ_0000326 expression was significantly elevated in BC cell lines and tissues, and circ_0000326 could promote BC cell growth and migration, and inhibit apoptosis. Dual-luciferase reporter gene assay confirmed that circ_0000326 and ETS1 could bind directly to miR-338-3p. Furthermore, circ_0000326 sponged miR-338-3p and up-regulated ETS1 expression. ETS1 was associated with the activation of PI3K/AKT pathway. Moreover, circ_0000326 could activate PI3K/AKT pathway by miR-338-3p/ETS1 axis. Collectively, circ_0000326/miR-338-3p/ETS1/PI3K/AKT pathway is involved in regulating BC progression.

Preoperative prediction of muscular invasiveness of bladder cancer with radiomic features on conventional MRI and its high-order derivative maps.

PURPOSE: To determine radiomic features which are capable of reflecting muscular invasiveness of bladder cancer (BC) and propose a non-invasive strategy for the differentiation of muscular invasiveness preoperatively. METHODS: Sixty-eight patients with clinicopathologically confirmed BC were included in this retrospective study. A total of 118 cancerous volumes of interest (VOI) were segmented from patients' T2 weighted MR images (T2WI), including 34 non-muscle invasive bladder carcinomas (NMIBCs, stage

Radiomics assessment of bladder cancer grade using texture features from diffusion-weighted imaging.

PURPOSE: To 1) describe textural features from diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps that can distinguish low-grade bladder cancer from high-grade, and 2) propose a radiomics-based strategy for cancer grading using texture features. MATERIALS AND METHODS: In all, 61 patients with bladder cancer (29 in high- and 32 in low-grade groups) were enrolled in this retrospective study. Histogram- and gray-level co-occurrence matrix (GLCM)-based radiomics features were extracted from cancerous volumes of interest (VOIs) on DWI and corresponding ADC maps of each patient acquired from 3.0T magnetic resonance imaging (MRI). A Mann-Whitney U-test was applied to select features with significant differences between low- and high-grade groups (P < 0.05). Then support vector machine with recursive feature elimination (SVM-RFE) and classification strategy was adopted to find an optimal feature subset and then to establish a classification model for grading. RESULTS: A total 102 features were derived from each VOI and among them, 47 candidate features were selected, which showed significant intergroup differences (P < 0.05). By the SVM-RFE method, an optimal feature subset including 22 features was further selected from candidate features. The SVM classifier using the optimal feature subset achieved the best performance in bladder cancer grading, with an area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity of 0.861, 82.9%, 78.4%, and 87.1%, respectively. CONCLUSION: Textural features from DWI and ADC maps can reflect the difference between low- and high-grade bladder cancer, especially those GLCM features from ADC maps. The proposed radiomics strategy using these features, combined with the SVM classifier, may better facilitate image-based bladder cancer grading preoperatively. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1281-1288.

Three-dimensional texture features from intensity and high-order derivative maps for the discrimination between bladder tumors and wall tissues via MRI.

PURPOSE: This study aims to determine the three-dimensional (3D) texture features extracted from intensity and high-order derivative maps that could reflect textural differences between bladder tumors and wall tissues, and propose a noninvasive, image-based strategy for bladder tumor differentiation preoperatively. METHODS: A total of 62 cancerous and 62 wall volumes of interest (VOI) were extracted from T2-weighted MRI datasets of 62 patients with pathologically confirmed bladder cancer. To better reflect heterogeneous distribution of tumor tissues, 3D high-order derivative maps (the gradient and curvature maps) were calculated from each VOI. Then 3D Haralick features based on intensity and high-order derivative maps and Tamura features based on intensity maps were extracted from each VOI. Statistical analysis and recursive feature elimination-based support vector machine classifier (RFE-SVM) was proposed to first select the features with significant differences and then obtain a more predictive and compact feature subset to verify its differentiation performance. RESULTS: From each VOI, a total of 58 texture features were derived. Among them, 37 features showed significant inter-class differences ([Formula: see text]). With 29 optimal features selected by RFE-SVM, the classification results namely the sensitivity, specificity, accuracy and area under the curve (AUC) of the receiver operating characteristics were 0.9032, 0.8548, 0.8790 and 0.9045, respectively. By using synthetic minority oversampling technique to augment the sample number of each group to 200, the sensitivity, specificity, accuracy an AUC value of the feature selection-based classification were improved to 0.8967, 0.8780, 0.8874 and 0.9416, respectively. CONCLUSIONS: Our results suggest that 3D texture features derived from intensity and high-order derivative maps can better reflect heterogeneous distribution of cancerous tissues. Texture features optimally selected together with sample augmentation could improve the performance on differentiating bladder carcinomas from wall tissues, suggesting a potential way for tumor noninvasive staging of bladder cancer preoperatively.

Quantitative Analysis of Bladder Wall Thickness for Magnetic Resonance Cystoscopy.

OBJECTIVE: To find an effective way for quantitative evaluation on wall thickness variation of human bladder with/without bladder tumor, a novel pipeline of thickness measurement and analysis for magnetic resonance (MR) cystography is proposed. METHODS: After the acquisition of volumetric bladder images with a high-resolution T2-weighted 3-D sequence, the inner and outer borders of the bladder wall were segmented simultaneously by a coupled directional level-set method. Then, the bladder wall thickness (BWT) was estimated using the Laplacian method. To reducing the influence of individual variation and urine filling on wall thickness, a thickness normalization using Z-score is performed. Finally, a parametric surface mapping strategy was applied to map thickness distribution onto a unified sphere surface, for quantitative intra- and intersubject comparison between bladders of different shapes. RESULTS: The proposed pipeline was tested with a database composed of MR bladder images acquired from 20 volunteers and 20 patients with bladder cancer. The results indicate that the thickness normalization step using Z-score makes the quantitative comparison of wall thickness quite possible and there is a significant difference on BWT between patients and volunteers. Using the proposed pipeline, we established a thickness template for a normal bladder wall based on dataset of all volunteers. CONCLUSION: As a first attempt to establish a general pipeline for bladder wall analysis, the presented work provides an effective way to achieve the goal of evaluating the entire bladder wall for detection and diagnosis of abnormality. In addition, it can be easily extended to quantitative analyses of other bladder features, such as, intensity-based or texture features.

Characterization of texture features of bladder carcinoma and the bladder wall on MRI: initial experience.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine textural features that show a significant difference between carcinomatous tissue and the bladder wall on magnetic resonance imaging (MRI) and explore the feasibility of using them to differentiate malignancy from the normal bladder wall as an initial step for establishing MRI as a screening modality for the noninvasive diagnosis of bladder cancer. MATERIALS AND METHODS: Regions of interest (ROIs) were manually placed on foci of bladder cancer and uninvolved bladder wall in 22 patients and on the normal bladder wall of 23 volunteers to calculate 40 known textural features. Statistical analysis was applied to determine the difference in these features in bladder cancer versus uninvolved bladder wall versus normal bladder wall of volunteers. The significantly different features were then analyzed using a support vector machine (SVM) classifier to determine their accuracy in differentiating malignancy from the bladder wall. RESULTS: Thirty-three of 40 features show significant differences between bladder cancer and the bladder wall. Nine of 40 features were significantly different in uninvolved bladder wall of patients versus normal bladder wall of volunteers. Further study indicates that seven of these 33 features were significantly different between uninvolved bladder wall of patients with early cancer and that of volunteers, whereas 15 of 33 features were different between that of patients with advanced cancer and normal wall. With the testing dataset consisting of ROIs acquired from patients, the classification accuracy using 33 textural features fed into the SVM classifier was 86.97%. CONCLUSION: The initial experience demonstrates that texture features are sensitive to reveal the differences between bladder cancer and the bladder wall on MRI. The different features can be used to develop a computer-aided system for the evaluation of the entire bladder wall.

Antitumor activity of a polysaccharide from Pleurotus eryngii on mice bearing renal cancer.

One water-soluble polysaccharide (PEPw), with an average molecular weight of 2.5×10(4)Da, was isolated from the fruiting bodies of Pleurotus eryngii and subjected to composition analysis and evaluated for the antitumor and immunomodulatory activity. PEPw was composed of arabinose, mannose and galactose in a molar ratio of 1.2:2.3:6.2 and had a backbone mainly consisting of 1,6-linked-Galp, 1,2,6-linked-Galp and 1,4-linked-Manp residues, which was occasionally terminated with terminal-Araf attached to O-2 of 1,2,6-linked-Galp residue. The animal experiment results showed that PEPw significantly increased relative thymus and spleen indices, promoted the spleen lymphocytes proliferation induced by ConA or LPS, elevated the activities of NK cell and CTL in spleen, and increased the serum concentration of TNF-α and IL-2 in Renca tumor-bearing mice. As a result, the tumor growth was significantly inhibited by PEPw treatment at the doses of 50, 100 and 200mg/kg in a dose-dependent manner. These data indicated that the anti-tumor activity of PEPw may be related to the activation of the immune response in tumor-bearing mice.

Meta-analysis shows strong positive association of the TNF-α gene with tumor stage in bladder cancer.

There is no consensus on the association between the tumor necrosis factor-α (TNF-α) gene promoter -308 A/G single nucleotide polymorphisms and bladder cancer risk. To obtain a more precise estimation of this correlation, we conducted a meta-analysis. The PubMed, MEDLINE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases were searched for relevant published studies. Seven case-control studies with a total of 1,311 cases and 1,436 controls were identified and analyzed. A notable correlation was observed between the TNF-α genotype and bladder cancer grade (AA+GA vs. GG; odds ratio 1.96, 95% confidence interval 1.37-2.80, p = 0.0002). In summary, this meta-analysis demonstrates that the TNF-α -308 AA+GA genotype may be a marker to the tumor-invasive stage of bladder cancer.

Antioxidant treatment with quercetin ameliorates erectile dysfunction in streptozotocin-induced diabetic rats.

Oxidative stress is demonstrated to be involved in the pathophysiological mechanism of erectile dysfunction (ED). Quercetin, a potent bioflavonoid, has been reported to have the antioxidant role. In the present study, we examined the effect of quercetin on ED and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection of STZ. The diabetic rats were then randomized to diabetic group and quercetin therapy groups which were treated with quercetin at different doses of 5, 20 and 50mg/kg per day respectively. At the end of the 8th week, erectile function was assessed by measuring the rise in intracavernous pressure (ICP) following cavernous nerve electrostimulation. Superoxide dismutase (SOD) activity, thiobarbituric acid-reacting substance (TBARS) and nitrite and nitrate (NOx) levels were measured in cavernosum tissue. Endothelial NO synthase (eNOS) expression was determined using Western blot method. ICP in diabetic rats was significantly decreased than that in controls. After treatment with quercetin at the doses of 20 and 50mg/kg, ICP was significantly increased compared to that in untreated diabetic rats. Decreased levels of SOD activity, NOx and eNOS expression, as well as elevated levels of TBARS were found in diabetic group compared with control group. Treatment with 20 and 50mg/kg quercetin improved SOD activity, NOx and TBARS levels in corpus cavernosum of diabetic rats. Decreased expression of eNOS in diabetic rats was only ameliorated by 50mg/kg quercetin treatment. Quercetin could ameliorate ED in diabetic rats by inhibiting oxidative stress.

Detrimental functions of IL-17A in renal ischemia-reperfusion injury in mice.

BACKGROUND: Renal ischemia-reperfusion (I/R) injury, as a common and clinically important problem, starts with direct damage caused by chemokines and inflammatory cytokines, which is aggravated by specific and nonspecific immune reactions. Recently, IL-17A has been considered to be in a uniquely powerful position between adaptive and innate immunity. The present study investigated the role of IL-17A in renal I/R injury in mice. METHODS: We measured the time-course of changes in plasma and renal IL-17A levels using a murine model of renal I/R injury. Then, the protective effect of monoclonal anti-IL-17A antibody, given intravenously at 30 min before or after renal I/R operation, on renal I/R injury was investigated. In addition, the levels of plasma and renal pro- and anti-inflammatory cytokines and chemokines were assessed. RESULTS: IL-17A was significantly increased in plasma and kidneys after renal I/R injury in mice. Furthermore, intravenous administration of neutralizing monoclonal anti-IL-17A antibody attenuated renal I/R injury by evaluating renal function and histopathology. In addition, administration of anti-IL-17A antibody substantially reduced the plasma and renal levels of many pro-inflammatory mediators (TNF-α, IL-6, high-mobility group box 1 (HMGB1), IL-1ß, IL-17A, macrophage inflammatory protein-1α (MIP-1α), and monocyte chemoattractant protein-1 (MCP-1), as well as increased the plasma and renal levels of anti-inflammatory cytokines IL-10 and transforming growth factor ß (TGF-ß). CONCLUSION: The above data suggest that IL-17A has a detrimental effect on renal I/R injury via facilitating the production of pro-inflammatory cytokines and chemokines as well as hampering the production of anti-inflammatory cytokines.

Impacts of intensive insulin therapy in patients undergoing heart valve replacement.

BACKGROUND AND AIMS: Cardiac surgery with cardioplegic cardiac arrest and cardiopulmonary bypass (CPB) is associated with severe stress response, systemic inflammatory response, and injury. This study was designed to investigate the effects of intensive insulin therapy on patients undergoing valve replacement with CPB. METHODS: One hundred nondiabetic inpatients undergoing valve replacement were randomly assigned to a control group or an intensive insulin therapy (IT) group. Plasma cytokine and cardiac troponin I (cTnI) levels were monitored perioperatively. RESULTS: Compared with the control group, the IT group had smaller increases in plasma concentrations of tumor necrosis factor α, interleukin 1ß (IL-1ß), IL-6, and cTnI, and had a more pronounced increase in IL-10 levels after the initiation of CPB. After surgery, the required inotropes were reduced in the IT group. In the IT group, the time of artificial ventilation and the postoperative length of stay in the hospital were markedly shortened; however, there were no significant differences between the IT and control groups in mortality and the rate of nosocomial infections of deep sternal wounds. CONCLUSIONS: IT can significantly attenuate the systemic inflammatory response and improve a damaged cardiac function, but it does not reduce the in-hospital mortality rate.

A20 is overexpressed in glioma cells and may serve as a potential therapeutic target.

OBJECTIVE: A20 is a TNF-inducible primary response gene, which has been found to have antiapoptotic function in several cancer cells. This study investigates A20 expression in human glioma tissues and four glioma cell lines, and its effect on tumorigenesis of glioma cells and a mouse tumor model. METHODS: Human glioma tissue samples and cells were subject to reverse transcription-PCR (RT-PCR), western blotting and immunohistochemistry. Glioma cells was tested by flow cytometry. A xenograft tumor model in mice was utilized to examine the knock-down effect of specific A20 siRNAs on tumorigenesis. RESULTS: A20 was overexpressed in clinical glioma tissue samples (63.9%) and correlated with clinical staging. All four human glioma cell lines expressed A20, among which U87 displayed the strongest expression signals. Inhibiting A20 expression by siRNAs in vitro reduced the growth rates of glioma cells and resulted in G1/S arrest and increased apoptosis. In a mouse tumor model, local administration of siRNA significantly suppressed solid tumor growth. CONCLUSIONS: A20 was overexpressed both in human glioma tissues and cell lines, and inhibiting A20 expression greatly slowed tumor cell growth in culture and in mice. These findings indicated that A20 is involved in tumorigenesis of human glioma, and may serve as a future therapeutic target.

Biphasic effect of androgens on prostate cancer cells and its correlation with androgen receptor coactivator dopa decarboxylase.

The aim of this study was to explore the mechanism underlying the dual effect of androgen on prostate cancer cells and further explore its correlation with dopa decarboxylase (DDC), an androgen receptor (AR) coactivator and a traditional neuroendocrine differentiation (NED) marker. Cell proliferation and cycling after treatment with synthetic nonmetabolizable androgen R1881 was determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method and flow cytometry. Differential gene expression was analyzed by cDNA microarrays. DDC expression during the dual effect of R1881 was further explored with microarray, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and enzyme activity assays. Proliferation of LNCaP cells was inhibited by 1 nM R1881 but stimulated by 0.1 nM R1881. Compared with the untreated cells, 320 (2.26%; 170 up-regulated, 150 down-regulated) and 4608 (32.65%; 2046 up-regulated, 2562 down-regulated) genes were found to be expressed differentially in the 1 nM and 0.1 nM R1881-treated cells, respectively. The results were partially confirmed by RT-PCR and Western blot. The DDC gene was down-regulated in the 1 nM R1881-treated cells and up-regulated in 0.1 nM R1881- and 30 nM hydroxyflutamide-treated cells. The enzymatic activity of DDC in the latter 2 groups was also strengthened. Meanwhile, the NED markers CgA and synaptophysin were not affected by these AR activators. R1881 had a dose-dependent biphasic effect on LNCaP cell proliferation. AR coactivator DDC was respectively down- and up-regulated in high and low concentrations of R1881. DDC up-regulation by exogenous AR activators is not accompanied by up-regulation of definitive NED markers.