Value of ultra-high b-value diffusion-weighted imaging for the evaluation of renal ischemia-reperfusion injury.

To explore the feasibility of ultra-high b-value diffusion-weighted imaging (ubDWI) in assessment of renal IRI. Thirty-five rabbits were randomized into a control group (n = 7) and a renal IRI group (n = 28). The rabbits in the renal IRI group underwent left renal artery clamping for 60 min. Rabbits underwent axial ubDWI before and at 1, 12, 24, and 48 h after IRI. Apparent diffusion coefficient (ADCst) were calculated from ubDWI with two b-values (b = 0, 1000 s/mm2). Triexponential fits were applied to calculate the pure diffusion coefficients (D), perfusion-related diffusion coefficient (D⁎), and ultra-high ADC (ADCuh). The interobserver reproducibility were evaluated. The repeated measurement analysis of variance and Spearman correlation analysis was used for statistical analysis. The ADCst, D, and ADCuh values showed good reproducibility. The ADCst, D, and D⁎ values of renal Cortex (CO) and outer medulla (OM) significantly decreased after IRI (all P < 0.05). The ADCuh values significantly increased from pre-IRI to 1 h after IRI (P < 0.05) and significantly declined at 24 h and 48 h after IRI (all P < 0.05). ADCuh was strongly positively correlated with AQP-1 in the renal CO and OM (ρ = 0.643, P < 0.001; ρ = 0.662, P < 0.001, respectively). ubDWI can be used to non-invasively evaluate early renal IRI, ADCuh may be adopted to reflect AQP-1 expression.

Automatic Urinary Stone Detection System for Abdominal Non-Enhanced CT Images Reduces the Burden on Radiologists.

To develop a fully automatic urinary stone detection system (kidney, ureter, and bladder) and to test it in a real clinical environment. The local institutional review board approved this retrospective single-center study that used non-enhanced abdominopelvic CT scans from patients admitted urology (uPatients) and emergency (ePatients). The uPatients were randomly divided into training and validation sets in a ratio of 3:1. We designed a cascade urinary stone map location-feature pyramid networks (USm-FPNs) and innovatively proposed a ureter distance heatmap method to estimate the ureter position on non-enhanced CT to further reduce the false positives. The performances of the system were compared using the free-response receiver operating characteristic curve and the precision-recall curve. This study included 811 uPatients and 356 ePatients. At stone level, the cascade detector USm-FPNs has the mean of false positives per scan (mFP) 1.88 with the sensitivity 0.977 in validation set, and mFP was further reduced to 1.18 with the sensitivity 0.977 after combining the ureter distance heatmap. At patient level, the sensitivity and precision were as high as 0.995 and 0.990 in validation set, respectively. In a real clinical set of ePatients (27.5% of patients contain stones), the mFP was 1.31 with as high as sensitivity 0.977, and the diagnostic time reduced by > 20% with the system help. A fully automatic detection system for entire urinary stones on non-enhanced CT scans was proposed and reduces obviously the burden on junior radiologists without compromising sensitivity in real emergency data.

Ultrasmall Nanoparticles Regulate Immune Microenvironment by Activating IL-33/ST2 to Alleviate Renal Ischemia-Reperfusion Injury.

Renal ischemia-reperfusion injury (IRI) is a common disease with high morbidity and mortality. Renal IRI can cause the disorder of immune microenvironment and reprograming the immune microenvironment to alleviate excessive inflammatory response is crucial for its treatment. Cytokine IL-33 can improve the immune inflammatory microenvironment by modulating both innate and adaptive immune cells, and serve as an important target for modulating immune microenvironment of renal IRI. Herein, we report that bilobetin-functionalized ultrasmall Cu2- x Se nanoparticles (i.e., CSPB NPs) can activate the PKA/p-CREB/IL-33/ST2 signaling pathway to regulate innate and adaptive immune cells for reprograming the immune microenvironment of IRI-induced acute kidney injury. The biocompatible CSPB NPs can promote the polarization of M1-like macrophages into M2-like macrophages, and the expansion of ILC2 and Treg cells by activating IL-33/ST2 to modulate the excessive immune inflammatory response of renal IRI. More importantly, they can rapidly accumulate at the injured kidney to significantly alleviate IRI. This work demonstrates that modulating the expression of cytokines to reprogram immune microenvironment has great potential in the treatment of renal IRI and other ischemic diseases.

Assessment of Transplant Renal Artery Stenosis with Non-contrast-Enhanced Magnetic Resonance Angiography: Comparison with Digital Subtraction Angiography.

RATIONALE AND OBJECTIVES: Early diagnosis of transplant renal artery stenosis (TRAS) is crucial for salvaging kidney function and improving patient prognosis. The purpose of this study was to evaluate image quality of non-contrast-enhanced MR angiography (NCE-MRA) and the value of NCE-MRA in evaluating TRAS compared to DSA. MATERIALS AND METHODS: In 60 patients with TRAS confirmed by DSA, the degree of TRAS was assessed using balanced triggered angiography non-contrast-enhanced (B-TRANCE) MR angiography and was compared to that of DSA. Image quality for NCE-MRA was assessed independently by two radiologists. The Wilcoxon signed-rank test was used to compare NCE-MRA with DSA in assessing TRAS degree. Specificity, sensitivity, accuracy, positive-predictive value (PPV), and negative-predictive value (NPV) of NCE-MRA for the detection of marked (≥50%) TRAS were calculated. RESULTS: The image quality of NCE-MRA based on the B-TRANCE technology of transplanted renal arteries was sufficient (excellent in 81.67%, good in 8.33%, moderate in 6.67%, and non-diagnostic in 3.33%) and had a high inter-observer reproducibility (Kappa=0.836). DSA helped identify severe, moderate, and mild stenosis in 6, 32, and 22 arteries, respectively. No significant difference in the extent of TRAS between NCE-MRA and DSA were observed (P = 0.317). The specificity, sensitivity, accuracy, PPV, and NPV of NCE-MRA in detecting marked (≥50%) TRAS were 90.91%, 100%, 96.55%, 94.74%, and 100%, respectively. CONCLUSION: NCE-MRA based on B-TRANCE technology has shown promising consistency with DSA in evaluating TRAS and yielding high sensitivity, specificity, and accuracy in assessing the severity of TRAS.

Serum folic acid: an effective indicator for arteriogenic erectile dysfunction.

Background: The present study is the first to explore the correlation between serum folic acid (FA) level and penile arterial peak systolic velocity (PSV) as measured via penile color Doppler ultrasonography (PDU), which directly reflects endothelial function in the penile artery. Materials and methods: A total of 244 consecutive erectile dysfunction (ED) patients and 72 healthy controls, recruited from the Andrology department and the Healthy Physical Examination Center of our hospital, respectively, from June 2020 to April 2022, were included in the study. Serum FA was measured in ED patients and healthy controls, and PDU examinations were conducted for all eligible ED patients. The Pearson method was used to evaluate the correlation between FA levels and PDU parameters in ED patients. A receiver operating characteristic (ROC) curve analysis was also performed to calculate the sensitivity and specificity of these parameters for prediction of arteriogenic ED. Results: After the PDU test, the average serum FA level among patients diagnosed with arteriogenic ED was 8.08 ± 2.64 ng/ml, lower than the average of 10.78 ± 2.87 ng/ml among healthy controls. There were no statistically significant inter-group differences on any basic parameters, including age, body mass index, fasting blood glucose, total cholesterol, and triglyceride. For further analysis, we divided the arteriogenic ED group into three subgroups by PSV range to compare serum FA levels among these subgroups. The mean FA levels in each of these groups were 5.97 ± 1.51ng/ml, and 8.21 ± 2.37ng/ml, and 10.55 ± 2.56ng/ml, while the corresponding PSV values were 15.75 ± 2.39cm/s, 23.53 ± 2.19cm/s, and 32.72 ± 1.64cm/s. Overall, a positive correlation between PSV and FA level was found among patients with arteriogenic ED (r=0.605, P<0.001). Furthermore, when FA level was used, with a cut-off value of 10.045 ng/ml, as a criterion to distinguish patients with arteriogenic ED from healthy controls, the area under the curve (AUC) was 0.772 (95% confidential interval: [0.696, 0.848]), for a sensitivity of 0.611 and specificity of 0.824. Conclusion: Serum FA level is positively correlated with PSV in ED patients, and has the ability to distinguish patients with arteriogenic ED from healthy controls. Taking these findings together, FA deficiency should be regarded as an independent risk factor for arteriogenic ED.

Using the "2 standard deviations" rule with Dixon MRI to differentiate renal cell carcinoma types.

BACKGROUND: Clear cell and non-clear cell renal cell carcinoma (RCC) are distinguishable based on microscopic fat, detectable by chemical shift MRI. However, these assessments are often subjective. Conversely, Dixon MRIs and the "2 standard deviations" rule (2SDR) are quantitative methods that may decrease diagnostic subjectivity. Therefore, this study assessed the value of the 2SDR for detecting microscopic fat and thus differentiating clear cell and non-clear cell RCC using Dixon MRI. METHODS: This retrospective study included patients with RCC who underwent preoperative Dixon MRI. The patients were grouped based on tumor type: clear cell RCC and non-clear cell RCC. The 2SDR value was calculated based on in-phase and opposed-phase images and then compared between the two groups. 2SDR values >0 indicated clear cell RCCs, whereas values <0 indicated non-clear cell RCC. RESULTS: We included 151 patients; 114 patients had clear cell RCC, of which 106 had a 2SDR value >0. Furthermore, 37 patients had non-clear cell RCC, of which 3 had a 2SDR value >0. The 2SDR value was significantly higher in the clear cell RCC group than in the non-clear cell RCC group (p = 0.000). Overall, 93.0% (106/114) and 8.1% (3/37) of patients with clear cell and non-clear cell RCC, respectively, had microscopic fat. The evaluation indices for this 2SDR method were: accuracy: 92.72%, sensitivity: 92.98%, specificity: 91.89%, positive predictive value: 97.25%, and negative predictive value: 80.95%. CONCLUSIONS: 2SDR values calculated from Dixon magnetic resonance images can differentiate clear cell from non-clear cell RCCs by detecting microscopic fat. PRECIS: The "2 standard deviations" rule value calculated from Dixon MR images differentiates clear cell from non-clear cell renal cell carcinoma with high efficiency by detecting microscopic fat.

IL1R2 promotes tumor progression via JAK2/STAT3 pathway in human clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is known as the most aggressive subtype of genitourinary cancers. The lack of effective therapies has prompted us to further explore the complex network of genes involved in ccRCC tumor progression and metastasis and to seek new biomarkers and therapeutic strategies to improve clinical outcomes. Interleukin-1 receptor type 2 (IL1R2), a decoy receptor of IL-1, is found to be differentially expressed in various tumors types recently. However, the role of IL1R2 in ccRCC has not been documented. Herein, we found that the expression of IL1R2 in ccRCC tissues was significantly increased as the tumor's Furman pathological grade was elevated. Compared to lower IL1R2 expression, ccRCC patients with high IL1R2 expression had a significantly worse OS rate. IL1R2 could serve as an independent prognostic predictor for ccRCC patients. Depletion of IL1R2 could inhibit cell proliferation, migration, invasion, and cell cycle arrest at the G1 phase, while overexpression of IL1R2 could reverse this effect. Moreover, depletion of IL1R2 led to changes and enrichment of several signaling pathways, as shown by RNA sequencing. We subsequently verified that Janus kinase 2 / signal transducer and activator of transcription 3 (JAK2/STAT3) pathway was involved in the IL1R2 mediated regulation of cellular functions of ccRCC cells and these functions were acted by the intracellular domain of IL1R2, not the extracellular domain. Our findings suggested that IL1R2 could serve as a potential therapeutic target for ccRCC progression and metastasis via its regulation of the JAK2/STAT3 signaling pathway.

Quantitative assessment of renal allograft pathologic changes: comparisons of mono-exponential and bi-exponential models using diffusion-weighted imaging.

BACKGROUND: Diffusion-weighted imaging (DWI) can noninvasively assess renal allograft pathologic changes that provide useful information for clinical management and prognostication. However, it is still unknown whether the bi-exponential model analysis of DWI signals is superior to that of the mono-exponential model. METHODS: Pathologic and DWI data from a total of 47 allografts were prospectively collected and analyzed. Kidney transplant interstitial fibrosis was quantified digitally. The severity of acute and chronic pathologic changes was semi-quantified by calculating the acute composite scores (ACS) and chronic composite score (CCS). Mono-exponential total apparent diffusion coefficient (ADCT), and the bi-exponential parameters of true diffusion (D) and perfusion fraction (fp) were acquired. The diagnostic performances of both mono-exponential and bi-exponential parameters were assessed and compared by calculating the area under the curve (AUC) from receiver-operating characteristic (ROC) curve analysis. RESULTS: ADCT, D, and fp were all significantly correlated with interstitial fibrosis, ACS, and CCS. Cortical fp discriminated mild from moderate and severe ACS with the largest AUC of 0.89 [95% confidence interval (CI), 0.77-0.96]. Noticeably, only cortical fp could differentiate severe ACS from mild-to-moderate ACS (P<0.001) with an AUC of 0.80 (95% CI, 0.65-0.90) and a sensitivity of 100% (95% CI, 66.4-100%). Strikingly, the joint use of D and fp in either the cortex or the medulla could achieve a sensitivity of 100% for identifying either mild or severe interstitial fibrosis. Meanwhile, the serial use of cortical D and cortical fp showed the largest specificity for identifying both mild [88.9% (95% CI, 70.8-97.6%)] and severe [84.4% (95% CI, 67.2-94.7%)] interstitial fibrosis. For identifying mild CCS, the AUC of medullary ADCT (0.90, 95% CI, 0.78-0.97) was similar to that of cortical D (0.81, 95% CI, 0.67-0.91) and fp (0.86, 95% CI, 0.73-0.94), but statistically larger than that of medullary D (P=0.005) and fp (P=0.01). Furthermore, the parallel use of cortical D and cortical fp could increase the sensitivity to 95.0% (95% CI, 75.1-99.9%), whereas serial use of medullary D and medullary fp could increase the specificity to 100% (95% CI, 87.2-100%). The AUCs for differentiating severe from mild and moderate CCS were statistically insignificant among all parameters in the cortex and medulla (P≥0.15). CONCLUSIONS: Cortical fp was superior to the ADCT for identifying both mild and severe acute pathologic changes. Nevertheless, ADCT was equal to or better than single D or fp for evaluating chronic pathologic changes. Thus, both monoexponential and bi-exponential analysis of DWI images are complementary for evaluating kidney allograft pathologic changes, and the combined use of D and fp can increase the sensitivity and specificity for discriminating allograft pathologic changes severity.

Significance of examined lymph-node count in accurate staging and long-term survival in patients undergoing radical prostatectomy: a population-based study.

PURPOSE: The number of examined lymph node (ELN) is regarded as the critical quality index for cancer care. We scrutinize the relationship among ELN number, accurate staging, and long-term survival in prostate cancer (Pca). METHODS: Population-based data on Pca patients in 2004-2015 from the US SEER database were investigated. The connection among ELN number and stage migration, overall survival (OS), and prostate cancer-specific survival (CSS) were evaluated by performing multivariable-adjusted logistic, Cox proportional hazards, and fine-gray competing-risk regression models, respectively. LOWESS smoother was used to fit the series of ELN number, odds ratios (OR), and hazard ratios (HR), while the Chow test was used to resolve the structural breakpoints. Subgroup and interaction analyses were performed in different risk populations. RESULTS: Overall, 84,838 patients were analyzed. Serial improvements were seen in stage migration (OR, 1.072, P < 0.001), OS (HR, 0.991; P < 0.001), and CSS (HR, 0.983; P < 0.001) per additional ELN after adjusting for confounders. Subgroup analysis revealed that the ELN number gains the most staging and survival benefits in high-risk population (P for interaction < 0.001). Cut-point analyses suggested that an optimal number of 12 ELNs, which was verified by the cumulative incidence curve, had a strong capability to distinguish different probabilities of CSS. CONCLUSIONS: Higher quantities of ELNs are related to more-accurate nodal staging and long-term survival of Pca patients undergoing RP. We highlight that 12 ELNs are the optimal cut-point for the high-risk population to investigate the quality of LN detection and stratifying postoperative prognosis.

Evaluation of renal dysfunction using texture analysis based on DWI, BOLD, and susceptibility-weighted imaging.

OBJECTIVE: To explore the value of texture analysis based on diffusion-weighted imaging (DWI), blood oxygen level-dependent MRI (BOLD), and susceptibility-weighted imaging (SWI) in evaluating renal dysfunction. METHODS: Seventy-two patients (mean age 53.72 ± 13.46 years) underwent MRI consisting of DWI, BOLD, and SWI. According to their estimated glomerular filtration rate (eGFR), the patients were classified into either severe renal function impairment (sRI, eGFR < 30 mL/min/1.73 m2), non-severe renal function impairment (non-sRI, eGFR ≥ 30 mL/min/1.73 m2, and < 80 mL/min/1.73 m2), or control (CG, eGFR ≥ 80 mL/min/1.73 m2) groups. Thirteen texture features were extracted and then were analyzed to select the most valuable for discerning the three groups with each imaging method. A ROC curve was performed to compare the capacities of the features to differentiate non-sRI from sRI or CG. RESULTS: Six features proved to be the most valuable for assessing renal dysfunction: 0.25QuantileDWI, 0.5QuantileDWI, HomogeneityDWI, EntropyBOLD, SkewnessSWI, and CorrelationSWI. Three features derived from DWI (0.25QuantileDWI, 0.5QuantileDWI, and HomogeneityDWI) were smaller in sRI than in non-sRI; EntropyBOLD and CorrelationSWI were smaller in non-sRI than in CG (p < 0.05). 0.25QuantileDWI, 0.5QuantileDWI, and HomogeneityDWI showed similar capacities for differentiating sRI from non-sRI. Similarly, EntropyBOLD and CorrelationSWI showed equal capacities for differentiating non-sRI from CG. CONCLUSION: Texture analysis based on DWI, BOLD, and SWI can assist in assessing renal dysfunction, and texture features based on BOLD and SWI may be suitable for assessing renal dysfunction during early stages. KEY POINTS: • Texture analysis based on MRI techniques allowed for assessing renal dysfunction. • Texture features based on BOLD and SWI, but not DWI, may be suitable for assessing renal function impairment during early stages. • SWI exhibited a similar capacity to BOLD for assessing renal dysfunction.

Assessment of delayed graft function using susceptibility-weighted imaging in the early period after kidney transplantation: a feasibility study.

PURPOSE: This study aimed to explore the feasibility of susceptibility-weighted imaging (SWI) for evaluating delayed graft function (DGF) during the early posttransplantation period. METHODS: Sixty-nine recipients who accepted allograft renal transplantation underwent SWI during the second posttransplantation week. Renal allograft function was estimated via the glomerular filtration rate. Recipients with and without DGF were identified. For each transplanted kidney, the presence of abnormal signal intensity lesions (ASILs), excluding benign lesions, on SWI was assessed. Renal allograft function was compared between the recipients with and without ASILs. The correlation between ASILs and renal allograft function was tested by Spearman's rank correlation analysis. RESULTS: Thirty-four recipients were diagnosed with DGF, while 35 recipients showed no DGF. In the DGF group, 16 recipients had low-intensity ASILs, primarily at the corticomedullary junction of transplanted kidneys on SWI, and no ASILs were found in 18 recipients. In the non-DGF group, none of the recipients showed ASILs on SWI. In the DGF group, the renal allograft function among the 16 recipients with low-intensity ASILs was significantly lower than that among the other 18 recipients (8.5 ± 4.2 vs. 19.7 ± 9.7 mL/min, P < 0.001). The presence of low-intensity ASILs on SWI showed a moderate negative correlation with renal allograft function in recipients with DGF (r = - 0.553, P = 0.001). CONCLUSION: SWI can be used to evaluate DGF in the early post-kidney transplantation period.

Evaluating Renal Fibrosis with R2* Histogram Analysis of the Whole Cortex in a Unilateral Ureteral Obstruction Model.

RATIONALE AND OBJECTIVES: The aim of this study was to use histogram analysis to assess the correlation between blood oxygen-level dependent magnetic resonance imaging (BOLD-MRI) and renal fibrosis induced by unilateral ureteral obstruction (UUO) in an animal model for a long experimental period. MATERIALS AND METHODS: The rabbits were randomly divided into a control group (n = 6) and a UUO group (n = 30). The rabbits in the UUO group underwent left ureteral obstruction surgery. BOLD-MRI examinations were performed at 2, 4, 6, and 8 weeks after ligation. After the examinations, nephrectomy was performed for histologic evaluation. Histogram analysis of the left renal cortex (C) R2* values was performed to measure the mean, median, 10th percentile, 90th percentile, skewness, and kurtosis for all kidneys. Masson trichrome staining was used to assess the percentage of fibrotic area. RESULTS: The histogram R2* values of the mean, median, 10th percentile, and 90th percentile at week 2 were all lower than those at baseline. Over the course of UUO progression, there were statistical differences between the histogram R2* values at any other two time points, except between weeks 4 and 6, and weeks 6 and 8. A close correlation was found between the percentage of fibrotic area and R2* values (mean: F = 21.49, p = 0.0001, R2 = 0.49, median: F = 30.07, p < 0.0001, R2 = 0.58, 10th percentile: F = 31.02, p < 0.0001, R2 = 0.59, 90th percentile: F = 24.13, p < 0.0001, R2 = 0.52). CONCLUSION: BOLD-MRI could reflect the formation and progression of renal fibrosis in a rabbit UUO model; however, the value of BOLD-MRI in the long-term evaluation of fibrosis is limited.

Bromodomain-Containing Protein 4 (BRD4) Inhibition Sensitizes Palomid 529-Induced Anti-Renal Cell Carcinoma Cell Activity in Vitro and in Vivo.

BACKGROUND/AIMS: Mammalian target of rapamycin (mTOR) is a valuable treatment target of renal cell carcinoma (RCC). Palomid 529 is a novel mTORC1/2 dual inhibitor. METHODS: RCC cells were treated with different concentrations of Palomid 529. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by BrdU ELISA assay. Cell apoptosis was tested by the Hoechst-33342 nuclei staining assay and Histone DNA ELISA assay. mTOR signaling was tested by Western blotting assay and co-immunoprecipitation (IP) assay. The SCID mouse 786-O xenograft model was established to test RCC cell growth in vivo. RESULTS: Palomid 529 exerted cytotoxic, anti-proliferative and pro-apoptotic activities in 786-O RCC cells. Palomid 529 disassembled mTORC1/2, causing de-phosphorylation of mTORC1/2 substrates. Bromodomain-containing protein 4 (BRD4) is a primary resistant factor of Palomid 529. Palomid 529-induced 786-O cell apoptosis was sensitized by BRD4 inhibitors or BRD4 silencing, but inhibited with BRD4 over-expression. Palomid 529-induced cytotoxicity in the primary human RCC cells was negatively correlated with BRD4 expression level. In vivo, Palomid 529 i.p. administration inhibited 786-O xenograft tumor growth in SCID mice. Its anti-tumor activity was further sensitized by co-administration of the BRD4 inhibitor JQ1. Cconclusion: Palomid 529 inhibits RCC cell growth in vitro and in vivo. BRD4 inhibition could further sensitize Palomid 529 against RCC cells.

CT-based radiomic model predicts high grade of clear cell renal cell carcinoma.

PURPOSE: To compare the predictive models that can incorporate a set of CT image features for preoperatively differentiating the high grade (Fuhrman III-IV) from low grade (Fuhrman I-II) clear cell renal cell carcinoma (ccRCC). MATERIAL AND METHODS: One hundred and fourteen patients with ccRCC treated with a partial or radical nephrectomy were enrolled in the training cohort. The six non-texture features, including Pseudocapsule, Round mass, maximal tumor diameter (Diametermax), intratumoral artery (Arterytumor), enhancement value of the tumor (TEV) and relative TEV (rTEV), were assessed for each tumor. The texture features were extracted from the CT images of the section with the largest area of renal mass at both corticomedullary and nephrographic phases. The least absolute shrinkage and selection operator (LASSO) was used to screen the most valuable texture features to calculate a texture score (Texture-score) for each patient. A logistic regression model was used in the training cohort to discriminate the high from low grade ccRCC at nephrectomy. The predictors would include all non-texture features in Model 1, all non-texture features and Texture-score in Model 2, and Texture-score in Model 3. The performance of the predictive models were tested and compared in an independent validation cohort composed of 92 cases with ccRCC. RESULTS: Inter-rater agreement was good for each non-texture feature and Texture-score (the concordance correlation coefficient or Kappa coefficient > 0.70). The Texture-score was calculated via a linear combination of the 4 selected texture features. The three models shown good discrimination of the high from low grade ccRCC in the training cohort and the area under receiver operating characteristic curve (AUC) was 0.826 in Mode 1, 0.878 in Model 2 and 0.843 in Model 3, and a significant different AUC was found between Model 1 and Model 2. Application of the predictive models in the validation cohort still gave a discrimination (AUC > 0.670), and the Texture-score based models with or without the non-texture features (Model 2 and 3) showed a better discrimination of the high from low grade ccRCC (P < 0.05). CONCLUSION: This study presented the Texture-score based models can facilitate the preoperative discrimination of the high from low grade ccRCC.

Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires AMPK Activation.

We here evaluated the antiesophageal cancer cell activity by the antifungal drug itraconazole. Our results show that µg/mL concentrations of itraconazole potently inhibited survival and proliferation of established (TE-1 and Eca-109) and primary human esophageal cancer cells. Itraconazole activated AMPK signaling, which was required for subsequent esophageal cancer cell death. Pharmacologic AMPK inhibition, AMPKα1 shRNA, or dominant negative mutation (T172A) almost completely abolished itraconazole-induced cytotoxicity against esophageal cancer cells. Significantly, itraconazole induced AMPK-dependent autophagic cell death (but not apoptosis) in esophageal cancer cells. Furthermore, AMPK activation by itraconazole induced multiple receptor tyrosine kinases (RTKs: EGFR, PDGFRα, and PDGFRß), lysosomal translocation, and degradation to inhibit downstream Akt activation. In vivo, itraconazole oral gavage potently inhibited Eca-109 tumor growth in SCID mice. It was yet ineffective against AMPKα1 shRNA-expressing Eca-109 tumors. The in vivo growth of the primary human esophageal cancer cells was also significantly inhibited by itraconazole administration. AMPK activation, RTK degradation, and Akt inhibition were observed in itraconazole-treated tumors. Together, itraconazole inhibits esophageal cancer cell growth via activating AMPK signaling. Mol Cancer Ther; 17(6); 1229-39. ©2018 AACR.

Fat status detection and histotypes differentiation in solid renal masses using Dixon technique.

PURPOSE: To detect fat status and differentiate histotypes of renal masses by using Dixon technique. MATERIALS AND METHODS: This study included 134 solid renal masses. Signal intensity index (SII) and fat fraction (FF) in different histotypes were compared. RESULTS: Only angiomyolipoma (AML), clear cell renal cell carcinoma (RCC), and papillary RCC were confirmed to contain fat. The FF of 16.8% can effectively differentiate AML from clear cell RCC, so did the SII of 9.2% can differentiate clear cell RCC from non-clear cell RCC and rare benign histotypes. CONCLUSION: Dixon technique successfully evaluated the fat status and histotypes of renal masses.

Longitudinal assessment of rabbit renal fibrosis induced by unilateral ureteral obstruction using two-dimensional susceptibility weighted imaging.

BACKGROUND: Previous studies indicated that two-dimensional-susceptibility weighted imaging (2D-SWI) could serve as a useful biomarker for differentiating the grade of liver fibrosis. PURPOSE: To evaluate the feasibility of 2D-SWI in the dynamic quantification of renal fibrosis in a rabbit model. STUDY TYPE: Longitudinal study. ANIMAL MODEL: Twenty-Four New Zealand White Rabbits including control group (n = 4); and renal fibrosis group (n = 20), by means of a unilateral ureteral obstruction (UUO) model. FIELD STRENGTH/SEQUENCE: The 3.0 T SWI using a 2D gradient-echo sequence. ASSESSMENT: The relative SWI signal ratio(r) of cortical and medulla (r = SIrenal /SImuscle ) was longitudinally assessed before ligation and on weeks 2, 4, 6, and 8 following ligation. Sirius Red staining was used to assess the degree of fibrosis in five high-power fields. STATISTICAL TESTS: The repeated measures of analysis of variance and linear regression analysis. RESULTS: Both the cortical and medullary r values were significantly higher in the UUO kidneys at week 2 compared with the kidneys before ligation. Over the course of UUO progression, significant changes occurred in the cortical and medullary r values in vivo and fibrosis scores in vitro (all P values < 0.05). The r values gradually decreased, while the fibrosis scores gradually increased over 8 weeks following ligation. The linear regression analysis showed a strong and significant correlation between cortical and medullary r values and the pathologic fibrosis scores (R2 = 0.91, 0.81, respectively). DATA CONCLUSION: The SWI sequence could provide a quantitative evaluation of renal fibrosis during UUO progression. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1572-1577.

Down-regulation of miR-605 promotes the proliferation and invasion of prostate cancer cells by up-regulating EN2.

AIMS: MicroRNA served as inhibitor for gene expression in various cancers. This study aimed to investigate the role of miR-605 and EN2 in prostate cancer (PCa). MATERIALS AND METHODS: In this research, the expression of miR-605 and EN2 protein in PCa tissues and cells were determined by qRT-PCR and western blot, respectively. The cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and the tumor cell invasion assay was accomplished with transwell system. Flow cytometry was used to analyze the cell cycle. The endogenous expression of miR-605 and EN2 was modulated by recombinant plasmids and cell transfection. Dual luciferase reporter assay was performed to determine the interaction between miR-605 and EN2 in PCa cells. KEY FINDINGS: The expression of miR-605 was lower in PCa tissue and cells than that in normal tissues and cells, while the expression of EN2 was just the opposite. Down-regulation of the EN2 by siRNA inhibited the proliferation and invasion of PC3 cells, and the cell cycle was arrested in G0/G1 phase. EN2 regulated the expression of E-cadherin and Vimentin through Snail and EN2 regulated the cell cycle and cell proliferation via PI3K/AKT pathway. MiR-605 inhibited the proliferation and invasion of PCa cells through targeting EN2. SIGNIFICANCE: EN2 is negatively regulated by miR-605, and down-regulation of miR-605 promotes the proliferation and invasion of PCa cells by up-regulating EN2, which leads to PCa development and progression.

Hydrogen Rich Water Attenuates Renal Injury and Fibrosis by Regulation Transforming Growth Factor-ß Induced Sirt1.

The current research was designed to study the role of hydrogen in renal fibrosis and the renal epithelial to mesenchymal transition (EMT) induced by transforming growth factor-ß1 (TGF-ß1). Hydrogen rich water (HW) was used to treat animal and cell models. Unilateral ureteral obstruction (UUO) was performed on Balb/c mice to create a model of renal fibrosis. Human kidney proximal tubular epithelial cells (HK-2 cells) were treated with TGF-ß1 for 36 h to induce EMT. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured to test renal function, in addition, kidney histology and immunohistochemical staining of alpha-smooth muscle actin (α-SMA) positive cells was performed to examine the morphological changes. The treatment with UUO induced a robust fibrosis of renal interstitium, shrink of glomerulus and partial fracture of basement membrane. Renal function was also impaired in the experimental group with UUO, with an increase of Scr and BUN in serum. After that, Western-blot was performed to examine the expression of α-SMA, fibronectin, E-cadherin, Smad2 and Sirtuin-1 (Sirt1). The treatment with HW attenuated the development of fibrosis and deterioration of renal function in UUO model. In HK-2 cells, the pretreatment of HW abolished EMT induced by TGF-ß1. The down-regulation the expression of Sirt1 induced by TGF-ß1 which was dampened by the treatment with HW. Sirtinol, a Sirt1 inhibitor, reversed the effect of HW on EMT induced by TGF-ß1. HW can inhibit the development of fibrosis in kidney and prevents HK-2 cells from undergoing EMT which is mediated through Sirt1, a downstream molecule of TGF-ß1.

Magnetic resonance imaging evaluation of renal ischaemia-reperfusion injury in a rabbit model.

NEW FINDINGS: What is the central question of this study? Renal ischaemia-reperfusion injury occurs in various clinical settings. The clinical diagnosis of ischaemia-reperfusion injury is routinely based on biochemical and haematological tests, which cannot evaluate the function of a single kidney. New magnetic resonance imaging techniques to identify the pathophysiological changes in the renal outer medulla were evaluated. What is the main finding and its importance? This study demonstrated that susceptibility-weighted imaging is a feasible non-invasive tool for imaging and evaluating physipathological changes in the renal outer medulla after ischaemia-reperfusion injury. The aim was to evaluate the feasibility of susceptibility-weighted imaging (SWI) as a tool to identify the changes in the renal outer medulla (OM) in a rabbit model of renal ischaemia-reperfusion injury (IRI). New Zealand rabbits were used (control group n = 10; IRI group n = 40). The rabbits in the IRI group were subjected to left renal artery clamping for 60 min. T2-weighted (T2WI) and SWI examinations were performed at 1, 12, 24 or 48 h after reperfusion (each n = 10). After the examinations, the kidneys were submitted to histological evaluation. The contrast-to-noise ratio (CNR) for the left renal OM was measured using T2WI and SWI. The T2WI and SWI scores of the integrity of the renal OM were evaluated. There were significant differences between T2WI CNRs and SWI CNRs in the control group and the IRI 1, 12 and 48 h time points (all P < 0.05). No significant difference was found between T2WI and SWI CNRs at IRI 24 h (P > 0.05). The mean SWI scores of renal OM in the IRI 1 and 12 h subgroups were both significantly lower than that in the control group (all P < 0.05). The only significant difference in the mean T2WI scores of renal OM was observed between the control and IRI 1 h groups (P < 0.05). Susceptibility-weighted imaging has a significant advantage in evaluation of healthy renal OM over conventional magnetic resonance imaging, and it is a feasible non-invasive tool for imaging and evaluating changes in the renal OM after IRI.