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Background To develop a machine learning (ML)-assisted model capable of accurately identifying patients with calculous pyonephrosis before making treatment decisions by integrating multiple clinical characteristics. Methods We retrospectively collected data from patients with obstructed hydronephrosis who underwent retrograde ureteral stent insertion, percutaneous nephrostomy (PCN), or percutaneous nephrolithotomy (PCNL). The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. We developed 5 ML-assisted models from 22 clinical features using logistic regression (LR), LR optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), support vector machine (SVM), extreme gradient boosting (XGBoost), and random forest (RF). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Decision curve analysis (DCA) was used to investigate the clinical net benefit associated with using the predictive models. Results A total of 322 patients were included, with 225 patients in the training dataset, and 97 patients in the testing dataset. The XGBoost model showed good discrimination with the AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.981, 0.991, 0.962, 1.000, 1.000, and 0.989, respectively, followed by SVM [AUC =0.985, 95% confidence interval (CI): 0.970-1.000], Lasso-LR (AUC =0.977, 95% CI: 0.958-0.996), LR (AUC =0.936, 95% CI: 0.905-0.968), and RF (AUC =0.920, 95% CI: 0.870-0.970). Validation of the model showed that SVM yielded the highest AUC (0.977, 95% CI: 0.952-1.000), followed by Lasso-LR (AUC =0.959, 95% CI: 0.921-0.997), XGBoost (AUC =0.958, 95% CI: 0.902-1.000), LR (AUC =0.932, 95% CI: 0.878-0.987), and RF (AUC =0.868, 95% CI: 0.779-0.958) in the testing dataset. Conclusions Our ML-based models had good discrimination in predicting patients with obstructed hydronephrosis at high risk of harboring pyonephrosis, and the use of these models may be greatly beneficial to urologists in treatment planning, patient selection, and decision-making.

Calcium oxalate (CaOx) crystal can trigger kidney injury, which contributes to the pathogenesis of nephrocalcinosis. The phenotypes of infiltrating macrophage may impact CaOx-mediated kidney inflammatory injury as well as crystal deposition. How aryl hydrocarbon receptor (AhR) regulates inflammation and macrophage polarization is well understood; however, how it modulates CaOx nephrocalcinosis remains unclear. Methods: Mice were intraperitoneally injected with glyoxylate to establish CaOx nephrocalcinosis model with or without the treatment of AhR activator 6-formylindolo(3,2-b)carbazole (FICZ). Positron emission tomography computed tomography (PET-CT) imaging, Periodic acid-Schiff (PAS) staining, and polarized light optical microscopy were used to evaluate kidney injury and crystal deposition in mice kidney. Western blotting, immunofluorescence, chromatin immunoprecipitation, microRNA-fluorescence in situ hybridization, and luciferase reporter assays were applied to analyze polarization state and regulation mechanism of macrophage. Results: AhR expression was significantly upregulated and negatively correlated with interferon-regulatory factor 1 (IRF1) and hypoxia inducible factor 1-alpha (HIF-1α) levels in a murine CaOx nephrocalcinosis model following administration of FICZ. Moreover, AhR activation suppressed IRF1 and HIF-1α levels and decreased M1 macrophage polarization in vitro. In terms of the mechanism, bioinformatics analysis and chromatin immunoprecipitation assay confirmed that AhR could bind to miR-142a promoter to transcriptionally activate miR-142a. In addition, luciferase reporter assays validated that miR-142a inhibited IRF1 and HIF-1α expression by directly targeting their 3'-untranslated regions. Conclusions: Our results indicated that AhR activation could diminish M1 macrophage polarization and promote M2 macrophage polarization to suppress CaOx nephrocalcinosis via the AhR-miR-142a-IRF1/HIF-1α pathway.

Objective To develop novel models for predicting extracapsular extension (EPE), seminal vesicle invasion (SVI), or upgrading in prostate cancer (PCa) patients using clinical parameters, biparametric magnetic resonance imaging (bp-MRI), and transrectal ultrasonography (TRUS)-guided systematic biopsies. Patients and methods We retrospectively collected data from PCa patients who underwent standard (12-core) systematic biopsy and radical prostatectomy. To develop predictive models, the following variables were included in multivariable logistic regression analyses: total prostate-specific antigen (TPSA), central transition zone volume (CTZV), prostate-specific antigen (PSAD), maximum diameter of the index lesion at bp-MRI, EPE at bp-MRI, SVI at bp-MRI, biopsy Gleason grade group, and number of positive biopsy cores. Three risk calculators were built based on the coefficients of the logit function. The area under the curve (AUC) was applied to determine the models with the highest discrimination. Decision curve analyses (DCAs) were performed to evaluate the net benefit of each risk calculator. Results A total of 222 patients were included in this study. Overall, 83 (37.4%), 75 (33.8%), and 107 (48.2%) patients had EPE, SVI, and upgrading at final pathology, respectively. The addition of bp-MRI data improved the discrimination of models for predicting SVI (0.807 vs 0.816) and upgrading (0.548 vs 0.625) but not EPE (0.766 vs 0.763). Similarly, models including clinical parameters, bp-MRI data, and information on systematic biopsies achieved the highest AUC in the prediction of EPE (0.842), SVI (0.913), and upgrading (0.794), and the three corresponding risk calculators yielded the highest net benefit. Conclusion We developed three easy-to-use risk calculators for the prediction of adverse pathological features based on patient clinical parameters, bp-MRI data, and information on systematic biopsies. This may be greatly beneficial to urologists in the decision-making process for PCa patients.

The purpose of this study was to assess risk factors of urosepsis after minimally invasive percutaneous nephrolithotomy (MPCNL) for the treatment of upper urinary tract stones in patients with preoperative urinary tract infection (UTI) and to explore preventive measures. Between 2008 and 2016, patients with preoperative UTI who underwent MPCNL for upper urinary tract stones were retrospectively collected. Patients were divided into nonurosepsis and urosepsis groups. Perioperative outcomes of all patients were evaluated and compared between the two groups. Risk factors for post-MPCNL urosepsis were investigated using univariate and multivariate regression analysis. A total of 843 patients including 22 patients with postoperative urosepsis (urosepsis group) and 821 patients without urosepsis (nonurosepsis group) were finally included in this study. All patients with postoperative urosepsis were cured and discharged after treatment. In univariate analysis it was demonstrated that the incidence of urosepsis after MPCNL was significantly correlated with channel size (P=0.001), surgical time (P=0.003), as well as the tear of the collection system and percutaneous renal channel crossing the renal papilla (P=0.004). Moreover, multivariate analysis showed that smaller channel size (OR = 11.192, 95% CI: 2.425–51.650, P=0.002), longer surgical time (OR = 6.762, 95% CI: 1.712–17.844, P=0.008), and tear of collection system and percutaneous renal channel crossing the renal papilla (OR = 5.531, 95% CI 1.228–14.469, P=0.012) were independent risk factors for urosepsis following MPCNL in patients with preoperative UTI. In conclusion, in patients with preoperative UTI undergoing MPCNL for upper urinary tract stones, smaller channel size, prolonged operation time, as well as tear of the collection system and percutaneous renal channel crossing the renal papilla are independent risk factors for postoperative urosepsis. Therefore, it is indicated that, in clinical practice, it is of great significance to choose appropriate channel size and avoid renal injury and control surgical time to prevent the urosepsis after MPCNL in patients with preoperative UTI.

Histone lysine methyltransferases (HMT) comprise a subclass of epigenetic regulators; dysregulation of these enzymes affects gene expression, which may lead to tumorigenesis. Here, we performed an integrated analysis of 50 HMTs in bladder cancer and found intrinsic links between copy number alterations, mutations, gene expression levels, and clinical outcomes. Through integrative analysis, we identified six HMT genes (PRDM9,ASH1L,SETD3,SETD5,WHSC1L1, and KMT2D) that may play a key role in the development and progression of bladder cancer. Of these six HMTs, histone lysine N-methyltransferase 2D (KMT2D) exhibited the highest mutation rate in bladder cancer. Our comparison of the mRNA and miRNA expression profiles of mutated and wild-type KMT2D suggested that two signaling pathways (FOX1-miR-1224-5p-DLK1 and HIF/GATA5-miR-133a-3p-DRD5) may mediate the tumor suppressive effect of the KMT2D mutation. In summary, our findings indicate that mutations in HMT genes, especially KMT2D mutation, may play a role in the development of bladder cancer.

Based on the hypothesis that bioscaffold permeability is a major factor in determining the outcome of histologically complete and functional bladder regeneration, we evaluated regeneration processes of four-layer porcine small intestinal submucosa (SIS) construct; and compared results between rat bladders augmented with single-layer SIS bioscaffolds. Sprague-Dawley female rats were subjected to hemi-cystectomy followed by anastomosis of a patch of either single- or four-layer porcine SIS. Permeability was analyzed in situ using magnetic resonance imaging (MRI) at post-operative days 7 and 14. Bladder sections excised at days 7, 14, 28, and 56 post-operation Samples were assessed by HE and Masson's trichrome stains. Urothelial differentiation was analyzed using cytokeratin AE1/AE3, and uroplakin III (UPIII). In addition, quantitative and qualitative evaluations of neutrophils, mast cells, eosinophils, and macrophages were performed using anti-myeloperoxidase, Alcian blue, Giemsa stain, and anti-CD68 staining methods, respectively. Four-layer SIS was consistently impermeable as evidenced by the absence of intravesical administered gadolinium with diethylenetriaminepentacetate (Gd-DTPA) contrast signal in peripheral regions of augmented bladders compared with single-layer SIS bioscaffold. Elevated and sustained eosinophil and neutrophil infiltrations were prominent in four-layered SIS-augmented bladders compared with single-layer SIS with comparable impermeability. Delayed but consistent urothelial regeneration and differentiation were observed in four-layer SIS-augmented bladders; and urothelial differentiation was observed at day 56 post-augmentation. In conclusion, four-layer SIS enacts an elevated inflammatory response along with extended urothelial regeneration. Four-layer SIS may activate a different but yet to be identified mechanism for inflammatory responses. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1960-1969, 2019.

Impaired oxidative metabolism is one of multi-variate factors leading to exercise intolerance in heart failure patients. The purpose of the study was to demonstrate the use of dynamic 31P magnetic resonance spectroscopy (MRS) and 31P magnetic resonance imaging (MRI) techniques to measure PCr resynthesis rate post-exercise as a biomarker for oxidative metabolism in skeletal muscle in HF patients and controls. In this prospective imaging study, we recruited six HF patients and five healthy controls. The imaging protocol included 31P-MRS, spectrally selective 3D turbo spin echo for 31P-MRI, and Dixon multi-echo GRE for fat–water imaging on a 3 T clinical MRI scanner. All the subjects were scanned pre-exercise, during plantar flexion exercise, and post-exercise recovery, with two rounds of exercise for 31P -MRS and 31P-MRI, respectively. Unpaired t-tests were used to compare 31P-MRS and 31P-MRI results between the HF and control cohorts. The results show that PCr resynthesis rate was significantly slower in the HF cohort compared to the controls using 31P-MRS (P = 0.0003) and 31P-MRI (P = 0.0014). 31P-MRI showed significant differences between the cohorts in muscle groups (soleus (P = 0.0018), gastrocnemius lateral (P = 0.0007) and gastrocnemius medial (P = 0.0054)). The results from this study suggest that 31P-MRS/31P-MRI may be used to quantify lower leg muscle oxidative metabolism in HF patients, with 31P-MRI giving an additional advantage of allowing further localization of oxidative metabolism deficits. Upon further validation, these techniques may serve as a potentially useful clinical imaging biomarker for staging and monitoring therapies in HF-patients.

Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5′ caps and 3′ poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients’ survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-020-01300-8.

To compare the safety, effectiveness, and feasibility of contrast-enhanced ultrasound (CEUS) versus conventional ultrasound-guided percutaneous nephrolithotomy (PCNL) in patients with nondilated collecting system.Between July 2018 and July 2020, 160 kidney stone patients with nondilated collecting system planned for PCNL were randomly assigned into two groups, CEUS with retrograde ureteral contrast injection and conventional ultrasound with retrograde ureteral normal saline injection. Patient's demographics, the success rate of puncture, success rate of a single-needle puncture, number of punctures, puncture time, perioperative outcomes, stone-free rate, and incidence of complications were compared.The success rate of a single-needle puncture for CEUS-guided PCNL was higher than that in the conventional ultrasound group (88.5% vs. 73.7%, p = 0.02). Patients performed with CEUS-guided PCNL required less needle passes (p = 0.02), shorter needle puncture time (p = 0.031), and shorter channel establishment time (p = 0.04) than those guided with conventional ultrasound. The postoperative hemoglobin decrease in the CEUS-guided PCNL group was less than that of the control group (p = 0.02). There was no significant difference in operating time, length of hospital stays, kidney function change, and complications between the two groups (p0.05). The 1-month stone-free rate was 94.9% in the CEUS group and 90.8% in the control group (p0.05).Compared with conventional ultrasound, CEUS-guided PCNL may facilitate ultrasound-guided PCNL for patients without hydronephrosis, and benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop.Chinese Clinical Trial Registry: ChiCTR1800016981 KEY POINTS: • Compared with conventional ultrasound, CEUS-guided PCNL is a safe and efficacious procedure for kidney stone patients with nondilated collecting system. • Compared with conventional ultrasound, CEUS-guided PCNL benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. • CEUS-guided PCNL associated with the more accurate needle puncture and acceptable complications.

Hailang Liu,1 Kun Tang,1 Ejun Peng,1 Liang Wang,2 Ding Xia,1 Zhiqiang Chen1 1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People’s Republic of China; 2Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People’s Republic of ChinaCorrespondence: Ding Xia; Zhiqiang ChenTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, Hubei, People’s Republic of ChinaEmail 3012904661@qq.com; lhl20180129@163.comObjective: This study aimed to develop a machine learning (ML)-assisted model capable of accurately predicting the probability of biopsy Gleason grade group upgrading before making treatment decisions.Methods: We retrospectively collected data from prostate cancer (PCa) patients. Four ML-assisted models were developed from 16 clinical features using logistic regression (LR), logistic regression optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), random forest (RF), and support vector machine (SVM). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Calibration plots and decision curve analysis (DCA) were performed to evaluate the calibration and clinical usefulness of each model.Results: A total of 530 PCa patients were included in this study. The Lasso-LR model showed good discrimination with an AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.776, 0.712, 0.679, 0.745, 0.730, and 0.695, respectively, followed by SVM (AUC=0.740, 95% confidence interval [CI]=0.690– 0.790), LR (AUC=0.725, 95% CI=0.674– 0.776) and RF (AUC=0.666, 95% CI=0.618– 0.714). Validation of the model showed that the Lasso-LR model had the best discriminative power (AUC=0.735, 95% CI=0.656– 0.813), followed by SVM (AUC=0.723, 95% CI=0.644– 0.802), LR (AUC=0.697, 95% CI=0.615– 0.778) and RF (AUC=0.607, 95% CI=0.531– 0.684) in the testing dataset. Both the Lasso-LR and SVM models were well-calibrated. DCA plots demonstrated that the predictive models except RF were clinically useful.Conclusion: The Lasso-LR model had good discrimination in the prediction of patients at high risk of harboring incorrect Gleason grade group assignment, and the use of this model may be greatly beneficial to urologists in treatment planning, patient selection, and the decision-making process for PCa patients.Keywords: prostate cancer, biopsy cores, Gleason grade group, upgrading, machine learning

Background We aim to determine the prevalence of hypervirulent Klebsiella pneumoniae (hvKp), which causes surgical site infections (SSIs), and describe the microbiological and molecular characteristics of hvKp isolates. Methods Non-duplicate K. pneumoniae strains were isolated from wound drainage specimens of postoperative patients at the Chinese PLA General Hospital between September 2008 and July 2017. Antimicrobial susceptibility, string test, pulsed-field gel electrophoresis (PFGE), and genome sequencing analyses were performed. Results Fifty-one K. pneumoniae strains were isolated from wound drainage specimens collected from postoperative patients. Twenty-six hvKp strains, including 17 (17/37, 46.0%) and 9 (9/14, 64.3%) hvKp strains, were isolated from 37 and 14 patients with SSIs and community-acquired infections (CAIs), respectively. Notably, 4 extended-spectrum beta-lactamase (ESBL)-producing hvKp strains (4/26, 15.4%) and 2 carbapenem-resistant hvKp strains (2/26, 7.7%) were found. Thirteen K1 serotype (13/26, 50.0%) and 7 K2 serotype (7/26, 26.9%) strains were identified. Phylogenetic analysis results showed that 13 K1 serotype isolates exhibited a high degree of clonality, while 7 K2 serotype strains were genetically unrelated. MLST analysis indicated that there was a strong correlation between ST23 and the K1 serotype. ST65, ST86, and ST375 were prevalent in K2 serotype strains. Almost all hvKp strains (24/26, 92.3%) harbored large virulence plasmids with a high degree of homology to pNTUH-K2044 and sizes ranging from 140 to 220 kbp. Conclusions HvKp strains were prevalent in SSIs. Effective surveillance and control measures should be implemented to prevent the dissemination of such organisms, including the ESBL-producing and carbapenem-resistant hvKp strains.

Objective. Hyperperfusion syndrome (HPS) after bypass surgery for moyamoya disease (MMD) mainly results from redistribution of blood flow, which leads to poor outcomes, while effective methods to predict HPS are still lacking. Indocyanine green (ICG) videoangiography can assess regional cerebral blood flow changes semiquantitatively with the application of FLOW 800 software. The purpose of this study was to investigate whether the intraoperative evaluation of local hemodynamic changes around anastomotic sites using FLOW 800 videoangiography mapping can predict the incidence of HPS and clinical outcomes. Methods. Of the patients who were diagnosed with MMD in our hospital between August 2018 and December 2019, who underwent superficial temporal artery-middle cerebral artery bypass surgeries, we investigated 65 hemispheres (in 62 patients) in which intraoperative ICG analysis was performed using FLOW 800 (Zeiss Meditec, Oberkochen, Germany) to evaluate the local cerebral hemodynamics before and after anastomosis. Regions of interest were set at more than 2 points on the brain surface according to the location and situation of recipient arteries in the surgical area. Peak cerebral blood volume (CBV), regional cerebral blood flow (CBF), and time to peak (TTP) were calculated from the selected points. As the data were available intraoperatively, anastomoses were performed in a suitable area. According to the occurrence of HPS, patients were divided into the asymptomatic and symptomatic groups, from which hemodynamic parameters were compared. Furthermore, ROC analysis was performed to determine the diagnostic accuracy of change rates in CBV, CBF, and TTP (i.e., ΔCBV, ΔCBF, and ΔTTP) for predicting HPS. Results. Data from the 62 patients were analyzed, and all patients were closely assessed during hospitalization after the procedures. The values of ΔCBV and ΔCBF were significantly higher in the symptomatic group (p<0.01), while ΔTTP is slightly lower in the symptomatic group with no statistical differences (p=0.72). Hemodynamic parameters including ΔCBV and ΔCBF, calculated by FLOW 800, had high sensitivity and specificity according to the ROC curve (ΔCBV: AUC=0.743, 95% CI, 0.605–0.881, p=0.002; ΔCBF: AUC=0.852, 95% CI, 0.750–0.954, p<0.01), which could be used as predictors for HPS. Conclusions. Intraoperative ICG-FLOW 800 videoangiography mapping is a safe method which can reflect hemodynamic characteristics in the surgical area for MMD, the findings of which correlate with the occurrence of HPS. Parameters including ΔCBV and ΔCBF are proven to be efficient in the prediction of HPS.

Medicine is an important application area for deep learning models. Research in this field is a combination of medical expertise and data science knowledge. In this paper, instead of 2D medical images, we introduce an open-access 3D intracranial aneurysm dataset, IntrA, that makes the application of points-based and mesh-based classification and segmentation models available. Our dataset can be used to diagnose intracranial aneurysms and to extract the neck for a clipping operation in medicine and other areas of deep learning, such as normal estimation and surface reconstruction. We provide a large-scale benchmark of classification and part segmentation by testing state-of-the-art networks. We also discuss the performance of each method and demonstrate the challenges of our dataset. The published dataset can be accessed here: https://github.com/intra3d2019/IntrA., Comment: Accepted by cvpr2020, camera-ready version will be uploaded later

PURPOSE To demonstrate the feasibility of the so-called quadrupolar jump-and-return (QJR) pulse sequence by assessing its performance on the contrast modification to knee cartilage and quality of fluid suppression in the knee joint in vivo at 7T. METHODS The right knee joints of five healthy volunteers (3 males: mean age = 32.4 ± 1.3 years; 2 females: mean age = 27.9 ± 1.0 years; mean age = 30.6 ± 2.7 years) were scanned on a 7T scanner with variation of the delay in the QJR sequence from 1 ms to 5 ms. For one healthy volunteer, the QJR scan with the delay of 3 ms and the inversion-recovery (IR) scan were performed. Numerical simulations were conducted to evaluate the effects of B0 - and B1 -field inhomogeneities and residual quadrupolar couplings on fluid suppression and tissue contrast, respectively. RESULTS The QJR sequence suppressed the fluid signal from the artery and produced the contrast of knee cartilage in vivo. Its performance was comparable to that of the conventional IR sequence. Numerical simulations suggested that the fluid suppression may not be affected much by field inhomogeneities but that a distribution of residual quadrupolar couplings and weak RF pulses may interfere with the clear interpretation of cartilage contrast. CONCLUSION This preliminary work demonstrated that the QJR pulse sequence produces contrast for knee cartilage while suppressing the fluid signal from the artery. The knee cartilage contrast and quality of fluid suppression obtained from the QJR sequence were comparable to those of the IR sequence. Magn Reson Med 80:641-647, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Augmentation enterocystoplasty remains the gold standard surgical bladder reconstruction procedure to increase the capacity and compliance of dysfunctional bladders. Since the use of the patient's intestine has severe risks of complications, alternative biodegradable matrices have been explored. Porcine small intestinal submucosa (SIS) has gained immense interests in bladder reconstruction due to its favorable properties. However, trials have shown inconsistent regeneration with SIS, attributed to the heterogeneity in microstructures and mechanical properties. We hypothesize that uneven SIS permeability to urine is a factor responsible for the inconsistency. We measured permeability to urine in situ using a contrast enhanced-magnetic resonance imaging (MRI), and evaluated urothelium regeneration using immunohistochemical staining of urothelial cell markers in SIS-augmented rat bladders. Results showed significant differences in permeability among SIS-augmented rat bladders. Commercial SIS scaffolds were then categorized into nonleaky and leaky groups based on MRI results. Hematoxylin and eosin staining showed higher numbers of inflammatory cells in leaky SIS on day 14 relative to nonleaky SIS. In addition, trichrome staining showed major changes in the distribution of collagen on day 28 between SIS-augmented bladder groups. Furthermore, expressions of urothelium-associated markers (cytokeratins AE1/AE3, claudin 4, and uroplakin III) were completed in bladders augmented with nonleaky SIS, whereas limited urothelial differentiation was noticed in leaky SIS-augmented bladders at post-augmentative day 14. These results show that scaffold permeability to urine may be responsible for variations in regenerative capacity of porcine SIS. Applications of MRI technique will be helpful to understand a relationship between biomaterial property and regenerative capacity. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1778-1787, 2018.

Abstract Triple-negative breast cancer (TNBC), defined as a tumor subtype that lacks ER, PR, and HER2, shows a poor prognosis due to its aggressive tumor biology and limited treatment options. Deregulation of Aurora kinase A (Aur-A), a member of the mitotic serine/threonine Aurora kinase family, and overactivation of the mTOR pathway commonly occur in multiple cancer types. We previously found that Aur-A activated the mTOR pathway and inhibited autophagy activity in breast cancer cell models. Whether and how Aur-A regulates mTOR in TNBC are still unclear. Here, we found that Aur-A and p-mTOR are highly expressed and positively associated with each other in TNBC cells and tissues. Inhibition or knockdown of Aur-A decreased p-mTOR and suppressed cell proliferation and migration, whereas overexpression of Aur-A increased p-mTOR levels and promoted cell proliferation and migration, which was significantly abrogated by simultaneous silencing of mTOR. Intriguingly, overexpression of Aur-A enhanced the expression of p-mTOR and p-ERK1/2, and silencing or inhibition of ERK1/2 blocked Aur-A-induced p-mTOR. However, silencing or inhibition of mTOR failed to reverse Aur-A-induced ERK1/2, indicating that Aur-A/ERK1/2/mTOR forms an oncogenic cascade in TNBC. We finally found that double inhibition of Aur-A and mTOR showed significant synergistic effects in TNBC cell lines and a xenograft model, indicating that Aur-A and mTOR are potential therapeutic targets in the TNBC subtype.

Purpose: To study the effects of magnetization transfer (MT, in which a semisolid spin pool interacts with the free pool), in the context of magnetic resonance fingerprinting (MRF). Methods: Simulations and phantom experiments were performed to study the impact of MT on the MRF signal and its potential influence on T1 and T2 estimation. Subsequently, an MRF sequence implementing off-resonance MT pulses and a dictionary with an MT dimension by incorporating a two-pool model were used to estimate the fractional pool size in addition to the B1+, T1, and T2 values. The proposed method was evaluated in the human brain. Results: Simulations and phantom experiments showed that an MRF signal obtained from a cross-linked bovine serum sample is influenced by MT. Using a dictionary based on an MT model, a better match between simulations and acquired MR signals can be obtained (NRMSE 1.3% versus 4.7%). Adding off-resonance MT pulses can improve the differentiation of MT from T1 and T2. In-vivo results showed that MT affects the MRF signals from white matter (fractional pool-size ~16%) and gray matter (fractional pool-size ~10%). Furthermore, longer T1 (~1060 ms versus ~860 ms) and T2 values (~47 ms versus ~35 ms) can be observed in white matter if MT is accounted for. Conclusion: Our experiments demonstrated a potential influence of MT on the quantification of T1 and T2 with MRF. A model that encompasses MT effects can improve the accuracy of estimated relaxation parameters and allows quantification of the fractional pool size., 11 pages, 5 figures, 2 tables, 2 supplements

Calcium-activated nucleotidase 1 (CANT1, belongs to the apyrase family, is widely expressed in various organs. However, the biological function of CANT1 remains poorly explored. In this study, we aimed to investigate the expression profile and functions of CANT1 in clear cell renal cell carcinoma (ccRCC). Our data show that the protein level of CANT1 was significantly higher in tumor tissues than in adjacent normal tissues. CANT1 silencing suppressed cell proliferation, migration, and invasion obviously in 769-P and 786-O cells, arrested cell cycle in S phase and promoted apoptosis in 769-P cells. In conclusion, the present study shows the different expression mode of CANT1 in human ccRCC tumor tissue and adjacent normal tissue, denotes the function of CANT1 in ccRCC cells and provides potential molecular mechanisms and pathways of CANT1 antitumor function in ccRCC.

Background: Intrarenal calcium oxalate (CaOx) crystals trigger inflammation and induce kidney tubular cell injury, which are processes that involve TLR4/NF-κB signalling. A recent genome-wide gene expression profile analysis of Randall's plaques in CaOx stone patients revealed that the expression of the long noncoding RNA H19 was significantly upregulated. However, to date, its role in kidney CaOx stones has not been reported. Method: GEO dataset were utilized to analyze gene expression profiles. Luciferase reporter assays, western blotting, qRT-PCR assay, immunoflfluorescence staining and ROS assay were employed to study the molecular mechanism of regulation of HMGB1/TLR4/NF-κB by H19 and miR-216b. In vitro and in vivo assays were performed to further confirm the the proinflammatory and prooxidative stress effects. Finding: H19 expression was significantly increased and positively corelated with the expression levels of HMGB1, TLR4 and NF-κB in the Randall's plaques and glyoxylate-induced CaOx nephrocalcinosis mouse model. H19 interacted with miR-216b and suppressed its expression. Additionally, miR-216b inhibited HMGB1 expression by directly binding its 3'-untranslated region (3'UTR). Moreover, the downregulation of H19 inhibited HMGB1, TLR4 and NF-κB expression and suppressed CaOx nephrocalcinosis-induced renal tubular epithelial cell injury, NADPH oxidase, and oxidative stress in vivo and in vitro. Interestingly, the inhibition of miR-216b can partially reverse the inhibitory effect of H19 knockdown on HMGB1 expression. Interpretation: We determined that H19 might serve as a facilitatory factor in the process of CaOx nephrocalcinosis-induced oxidative stress and renal tubular epithelial cell injury and revealed the mechanism by which the interaction between H19 and miR-216b could exert its effect via the HMGB1/TLR4/NF-κB pathway. Funding: This work was supported by the National Nature Science Foundation of China (8196030190, 8190033175, 81370805, 81470935, 81500534, and 81602236). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: All animal experiments were performed according to protocols approved by the Ethics Committee of Tongji Hospital, Huazhong University of Science and Technology.

For the treatment of large upper urinary stones percutaneous nephrolithotomy (PCNL) is generally considered the first choice, and Laparoscopic Stone Surgery (LSS) is an alternative. We aim to compare the efficiency and safety of PCNL with LSS, as far as the management of large upper urinary stones is concerned. A systematic search from Pubmed, Web of Science, Wiley Online Library and Elsevier was performed up to August 1, 2015 for the relevant published studies. After data extraction and quality assessment, meta-analysis was performed using the RevMan 5.3 software. 15 eligible trials evaluating LSS vs. PCNL were identified including 6 prospective and 9 retrospective studies with 473 patients undergoing LSS and 523 patients undergoing PCNL. Although LSS led to longer operative time (p = 0.01) and higher open conversion rate (p = 0.02), patients might benefit from significantly fewer overall complications (p = 0.03), especially lower bleeding rate (p = 0.02), smaller drop in hemoglobin level (p

In the field of sodium magnetic resonance imaging (MRI), inversion recovery (IR) is a convenient and popular method to select sodium in different environments. For the knee joint, IR has been used to suppress the signal from synovial fluids, which improves the correlation between the sodium signal and the concentration of glycosaminoglycans (GAGs) in cartilage tissues. For the better inversion of the magnetization vector under the spatial variations of the B0 and B1 fields, the IR sequence usually employ adiabatic pulses as the inversion pulse. On the other hand, it has been shown that RF shapes robust against the variations of the B0 and B1 fields can be generated by numerical optimization based on optimal control theory. In this work, we compare the performance of fluid-suppressed sodium MRI on the knee joint in vivo, between one implemented with an adiabatic pulse in the IR sequence and the other with the adiabatic pulse replaced by an optimal-control shaped pulse. While the optimal-control pulse reduces the RF power deposited to the body by 58%, the quality of fluid suppression and the signal level of sodium within cartilage are similar between two implementations.

Bipolar energy has recently been used as a common alternative to conventional monopolar transurethral resection of the bladder (TURB) while managing nonmuscle-invasive bladder cancer (NMIBC). We established a meta-analysis comparing the safety and efficacy of plasmakinetic bipolar and monopolar TURB for NMIBC.A systematic search of PubMed, MEDLINE, Web of Science, and China National Knowledge Infrastructure was performed up to March 1, 2015. Outcomes of interest assessing the two techniques included demographic and clinical baseline characteristics, perioperative variables, and complications.Eight eligible trials evaluating bipolar TURB (bTURB) versus monopolar TURB (mTURB) for NMIBC were identified including six randomized controlled trials (RCTs), one prospective study, and one retrospective study. The bTURB was associated with shorter operative time (P = 0.002), shorter hospital stay (P0.001), less established blood loss (P0.001), and shorter catheterization time (P = 0.004). There were fewer complications such as obturator nerve reflex (P0.001) and bladder perforation (P = 0.003) in the bTURB group. The postoperative recurrence rate in 2 years also showed advantages of bTURB over mTURB.Our data showed that bTURB appeared to be a safe and efficient method and had presented several advantages when compared with conventional mTURB in the management of NMIBC. As a promising technique, bTURB may be used as a preferable choice instead of mTURB for superficial bladder tumor.

This study is to establish a rabbit model for human prosthetic joint infection and biofilm formation. Thirty-two healthy adult rabbits were randomly divided into four groups and implanted with stainless steel screws and ultra-high molecular weight polyethylene (UHMWPE) washers in the non-articular surface of the femoral lateral condyle of the right hind knees. The rabbit knee joints were inoculated with 1 mL saline containing 0, 102, 103, 104 CFU of Staphylococcus epidermidis (S. epidermidis) isolated from the patient with total knee arthroplasty (TKA) infection, respectively. On the 14th postoperative day, the UHMWPE washers from the optimal 103 CFU group were further examined. The SEM examination showed a typical biofilm construction that circular S. epidermidis were embedded in a mucous-like matrix. In addition, the LCSM examination showed that the biofilm consisted of the polysaccharide stained bright green fluorescence and S. epidermidis radiating red fluorescence. Thus, we successfully create a rabbit model for prosthetic joint infection and biofilm formation, which should be valuable for biofilm studies.

Background The present study aimed to develop three nomograms by incorporating multiple clinical characteristics to identify those prostate cancer (PCa) patients with high probability of incorrect biopsy Gleason grade group (GG) before making treatment decisions. Methods We retrospectively collected data from PCa patients who underwent systematic biopsy and radical prostatectomy from January 2015 to December 2019 at Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology. Univariable and multivariable logistic regression analyses were preformed to identify independent risk factors associated with upgrading, upstaging and downgrading. By incorporating selected clinical parameters with high predictive value, we constructed three nomograms to predict the probability of upgrading, upstaging and downgrading. Discrimination of nomograms was evaluated by receiver operating characteristic (ROC) analysis with corresponding area under the curve (AUC). Decision curve analysis (DCA) and calibration curves were performed to evaluate calibration and the clinical usefulness of nomograms. Performance of the three nomograms was validated in the testing dataset. Results There were 585 PCa patients in total enrolled in this study who met the inclusion criteria. Of the 585 patients, the disease of 262 (44.8 %) was upgraded and 68 (11.6 %) was downgraded, and the disease of 67 (11.5 %) was upstaged. With regard to findings of multivariable analyses, patients’ age and biopsy GG (GG 2, GG 3, GG 4 versus GG 1) were significantly associated with upgrading. Moreover, maximum diameter of the index lesion (D-max), clinical T stage (cT3a, cT3b versus cT1−2), number of positive cores and total tumor length were significantly associated with upstaging. Furthermore, d -max, %fPSA (> 0.16 versus ≤ 0.16) and biopsy GG (GG 3, GG 4, GG 5 versus GG 2) were independent predictors of downgrading. The three nomograms displayed good calibration in respective calibration plots. ROC analyses showed good discrimination with satisfactory AUC values and DCA plots demonstrated that the upgrading-risk nomogram, upstaging-risk nomogram and downgrading-risk nomogram were all clinically useful. Conclusions The upgrading-risk nomogram, upstaging-risk nomogram, and downgrading-risk nomogram were developed and correctly predicted the probability of incorrect Gleason grade group assigned to patients undergoing systematic biopsy.

Paragangliomas of the urinary bladder (PUBs) are challenging catecholamine-producing neuroendocrine tumors. We aimed to facilitate their diagnosis and treatment by functional and anatomical classifications.Between April 2007 and September 2017, 31 cases from 2 centers were retrieved, in which the patients were pathologically diagnosed with PUB. Besides classifying them into functional and nonfunctional PUBs, functional PUBs were further subclassified into typical functional PUB (with typical symptoms and elevated catecholamines/metabolites levels) and atypical functional PUB. Anatomically, they were classified into submucosal, intramural, and subserosal PUBs.Functionally, these cases comprised 17 (54.8%) functional and 14 (45.2%) nonfunctional PUBs. Functional PUBs had significantly larger diameters than nonfunctional PUBs (P0.01). Of the 17 functional PUB cases, 8 were further subclassified into typical functional PUB, of which 4 were diagnosed without cystoscopy. Anatomically, these cases comprised 14 (45.2%) submucosal, 13 (41.9%) intramural, and 4 (12.9%) subserosal PUBs. Intramural and subserosal PUBs had significantly larger diameters and were more likely to be functional than submucosal PUBs (P0.05). Cystoscopy failed to detect the tumor in all patients with subserosal PUB. Besides all patients with intramural or subserosal PUB, 1 patient with submucosal PUB underwent partial cystectomy. The remaining 13 patients with submucosal PUB underwent transurethral resection of bladder tumor, 5 of whom required extra surgical intervention.By functional classification, omitting cystoscopy is feasible in the diagnosis of typical functional PUBs. By anatomical classification, intramural, and subserosal PUBs tend to be large and functional. Moreover, negative cystoscopic findings are not sufficient to exclude subserosal PUBs. Finally, not all submucosal PUBs are amenable to transurethral resection of bladder tumor.

Background/Aims: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically centered on paclitaxel-based chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates chemoresistance to paclitaxel by regulating target genes associated with drug resistance. Methods: We used data from The Cancer Genome Atlas to compare miR-34a expression levels in prostate cancer (PC) tissues with normal prostate tissues. The effects of miR-34a inhibition and overexpression on PC proliferation were evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was employed to identify the interactions between miR-34a and specific target genes. To determine the effects of up-regulation of miR-34a on tumor growth and chemo-resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice subcutaneously and evaluated the rate of tumor growth during paclitaxel treatment. We examined changes in the expression levels of miR-34a target genes JAG1 and Notch1 and their downstream genes via miR-34a transfection by quantitative reverse transcription PCR (qRT-PCR) and western blot assay. Results: miR-34a served as an independent predictor of reduced patient survival. MiR-34a was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to paclitaxel while miR-34a down-regulation resulted in chemoresistance to paclitaxel in vitro. A study of gain and loss in a series of functional assays revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the overexpression of miR-34a increased the sensitivity of PC-3PR cells to chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We found that miR-34a increased the chemosensitivity of PC-3PR cells by directly repressing the TCF1/ LEF1 axis. Conclusion: Our results showed that miR-34a is involved in the development of chemosensitivity to paclitaxel. By regulating the JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as potential predictive biomarkers of response to paclitaxel-based chemotherapy and/or therapeutic targets that will help to overcome chemoresistance at the mCRPC stage.

Chemical exchange saturation transfer (CEST) has been an intensive research area in MRI, providing contrast mechanisms for the amplified detection and monitoring of biomarkers and physiologically active molecules. In biological tissues and organs, many endogenous CEST agents coexist, and their CEST effects may overlap. The interpretation of such overlapped CEST effects can be addressed when the individual CEST effects originating from various metabolites are characterized. In this work, we present the in vitro measurements of the CEST effects from endogenous CEST agents that are commonly found in biological tissues and organs, at the external magnetic fields of 3 T and 7 T and under various pH conditions. Together with the proton NMR spectra measured at 11.7 T, these CEST effects have been evaluated in consideration of the chemical exchange rates, chemical shifts, and acidities of the labile protons. Amine protons of small metabolites might not be visible at 3 T, but some of them can be probed at 7 T, wherein their CEST effects may overlap with those from coexisting amide and hydroxyl protons.

Most simple renal cysts rarely require therapy. When it grows to such a large size, regardless of the presence of symptomatology, surgical intervention is required. In this study, we explored a new approach called percutaneous ureteroscopy laser unroofing for treatment renal cysts and evaluated its safety and efficacy. 71 simple renal cyst patients with surgical indications were enrolled, including 6 patients with a peripelvic cyst and 5 patients coexisting ipsilateral calculi. Under ultrasound guidance, an eighteen-gauge needle was placed inside the cyst cavity, and a guidewire was introduced followed by sequential dilation up to 28 F. The extra-parenchymal portion of cyst wall was dissociated and incised using either a Thulium or Holmium laser, and a pathological examination was performed. Renal calculi were treated simultaneously. For peripelvic cyst patients, one end of a double-J stent was inserted into the cyst cavity to prevent auto-closure. Mean of 11.7 months follow-up, the results showed that the cyst was completely resolved in 53 patients, its size was reduced to less than 50% in 15 patients, and treatment failed in only 3 anterior cyst patients, suggesting that percutaneous ureteroscopy laser unroofing is an effective and less invasive alternative for treatment of renal cysts in selected patients.

Androgen ablation is the standard of care prescribed to patients with advanced or metastatic prostate cancer (PCa) to slow down disease progression. Unfortunately, a majority of PCa patients under androgen ablation progress to castration-resistant prostate cancer (CRPC). Several mechanisms including alternative intra-prostatic androgen production and androgen-independent androgen receptor (AR) activation have been proposed for CRPC progression. Aldo-keto reductase family 1 member C3 (AKR1C3), a multi-functional steroid metabolizing enzyme, is specifically expressed in the cytoplasm of PCa cells; and positive immunoreactivity of the type A γ-aminobutyric acid receptor (GABAAR), an ionotropic receptor and ligand-gated ion channel, is detected on the membrane of PCa cells. We studied a total of 72 radical prostatectomy cases by immunohistochemistry, and identified that 21 cases exhibited positive immunoreactivities for both AKR1C3 and GABAAR. In the dual positive cancer cases, AKR1C3 and GABAAR subunit α1 were either expressed in the same cells or in neighboring cells. Among several possible substrates, AKR1C3 reduces 5α-dihydrotesterone (DHT) to form 5α-androstane-3α, 17β-diol (3α-diol). 3α-diol is a neurosteroid that acts as a positive allosteric modulator of the GABAAR in the central nervous system (CNS). We examined the hypothesis that 3α-diol-regulated pathological effects in the prostate are GABAAR-dependent, but are independent of the AR. In GABAAR-positive, AR-negative human PCa PC-3 cells, 3α-diol significantly stimulated cell growth in culture and the in ovo chorioallantoic membrane (CAM) xenograft model. 3α-diol also up-regulated expression of the epidermal growth factor (EGF) family of growth factors and activation of EGF receptor (EGFR) and Src as measured by quantitative polymerase chain reaction and immunoblotting, respectively. Inclusion of GABAAR antagonists reversed 3α-diol-stimulated tumor cell growth, expression of EGF family members, and activation of EGFR and Src to the level observed in untreated cells. Results from the present study suggest that 3α-diol may act as an alternative intra-prostatic neurosteroid that activates AR-independent PCa progression. The involvement of AKR1C3-mediated steroid metabolisms in modulating GABAAR activation and promoting PCa progression requires continued studies.

// Kun Tang 1, 2, * , Haoran Liu 1, 2, * , Kehua Jiang 1, 2 , Tao Ye 1, 2 , Libin Yan 1, 2 , Peijun Liu 1, 2 , Ding Xia 1, 2 , Zhiqiang Chen 1, 2 , Hua Xu 1, 2 and Zhangqun Ye 1, 2 1 Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 2 Institute of Urology of Hubei Province, Wuhan 430030, China * These authors have contributed equally to this work Correspondence to: Hua Xu, email: xuhuawhu@163.com Keywords: inflammatory response biomarkers, nephrolithiasis, percutaneous nephrolithotomy, metabolic syndrome, systemic inflammatory response syndrome Received: March 06, 2017 Accepted: July 12, 2017 Published: August 18, 2017 ABSTRACT Neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were promising biomarkers used to predict diagnosis and prognosis in various inflammatory responses diseases and cancers. However, there have been no reports regarding these biomarkers in kidney stone patients. This study aimed to evaluate the predictive value of inflammatory biomarkers for metabolic syndrome (MetS) and post-PCNL SIRS in nephrolithiasis patients. We retrospectively enrolled 513 patients with nephrolithiasis and 204 healthy controls. NLR, dNLR, LMR and PLR in nephrolithiasis patients were significantly higher than control group. Patients with renal stone have higher NLR, dNLR, LMR and PLR than those without. ROC curve analysis indicated NLR, dNLR, LMR and PLR for predicting patients with nephrolithiasis and MetS, displayed AUC of 0.730, 0.717, 0.627 and 0.606. Additionally, ROC curves, using post-PCNL SIRS as the end-point for NLR, dNLR, LMR and PLR with AUC of 0.831, 0.813, 0.723 and 0.685. Multivariate analysis revealed that NLR, dNLR represented independent factors for predicting post-PCNL SIRS. While LMR independently associated with MetS. These resluts demonstrate preoperative NLR, dNLR and LMR appears to be effective predictors of post-PCNL SIRS and LMR of MetS in nephrolithiasis patients.

To evaluate the potential of sodium MRI to detect changes over time of apparent sodium concentration (ASC) in articular cartilage in patients with knee osteoarthritis (OA). The cartilage of 12 patients with knee OA were scanned twice over a period of approximately 16 months with two sodium MRI sequences at 7 T: without fluid suppression (radial 3D) and with fluid suppression by adiabatic inversion recovery (IR). Changes between baseline and follow-up of mean and standard deviation of ASC (in mM), and their rate of change (in mM/day), were measured in the patellar, femorotibial medial and lateral cartilage regions for each subject. A matched-pair Wilcoxon signed rank test was used to assess significance of the changes. Changes in mean and in standard deviation of ASC, and in their respective rate of change over time, were only statistically different when data was acquired with the fluid-suppressed sequence. A significant decrease (p = 0.001) of approximately 70 mM in mean ASC was measured between the two IR scans. Quantitative sodium MRI with fluid suppression by adiabatic IR at 7 T has the potential to detect a decrease of ASC over time in articular cartilage of patients with knee osteoarthritis. • Sodium MRI can detect apparent sodium concentration (ASC) in cartilage • Longitudinal study: sodium MRI can detect changes in ASC over time • Potential for follow-up studies of cartilage degradation in knee osteoarthritis

A 52-year-old Hispanic male presented with hematuria and was later diagnosed with a large invasive high-grade urothelial cell carcinoma (UCC) of the urinary bladder, but with ambiguous pT1/pT2 staging regarding musclaris propria invasion by UCC. The conventional treatment including radical cystoprostatectomy followed by neoadjuvant chemotherapy with or without radiation therapy was presented. The patient decided to delay the standard therapy until a later stage, but elected to go through transurethral resection of bladder tumor (TURBT) without Bacillus Calmette-Guérin instillation. Following TURBT, the patient started oral Boswellia sacra gum resin (aka frankincense or Ru Xiang in Chinese) hydrodistillates (BSGRH) administration at 3 mL daily with lifestyle changes, and continued this regimen in the last 25 months. Within the first year after diagnosis, the patient experienced 2 recurrences. Recurrent tumors were removed by TURBT alone and both tumors were far smaller than the original one. After the second recurrence, the patient has no detectible cancer in the bladder based on cystoscopy for 14 months and has an intact genitourinary system. His liver and kidney functions are considered to be normal based on blood chemistry tests. This index case suggests that BSGRH may have cancer chemopreventive effects on UCC. The use of Boswellia-derived products in the management of cancer has been well document in other published studies, and boswellic acids have been suggested to be the major component. However, BSGRH contains very little boswellic acids. Demonstration of cancer chemoprevention using BSGRH is one step forward in isolating the key components other than boswellic acids in frankincense. The critical question as to whether these components can simultaneously activate multiple pathways in cancer cells to execute cancer suppression/cytotoxicity or prevention effects remains to be addressed. More studies including identification of key molecules, pharmacokinetics of major compounds, as well as long-term benefits and possible adverse effects will be needed to meet the guidelines of the US Food and Drug Administration for botanical drug development.

During the previous 2 decades, numerous surgical procedures have become available to treat osteochondral lesions of the talus. The objective of the present study was to use 7 Tesla (7T) magnetic resonance imaging (MRI) to quantify and compare T2 values (a marker of collagen architecture) of native tibiotalar cartilage and cartilage repair tissue in patients treated with a juvenile particulate allograft for osteochondral lesions of the talus. The institutional review board approved the present study, and all subjects provided written informed consent. We scanned the ankles of 7 cartilage repair patients using a 7T MRI scanner with a multi-echo spin-echo sequence to measure the cartilage T2 values. We assessed the cartilage T2 values in the talar repair tissue, adjacent native talar cartilage, and overlying tibial cartilage. We compared the differences between groups using the paired t test. The talar cartilage repair tissue demonstrated greater mean T2 relaxation times compared with the native adjacent talar cartilage (64.88 ± 12.23 ms versus 49.56 ± 7.82 ms; p = .043). The tibial cartilage regions overlying these talar cartilage regions demonstrated a trend toward greater T2 relaxation times (77.00 ± 31.29 ms versus 59.52 ± 7.89 ms; p = .067). 7T MRI can detect differences in T2 values in cartilage repair tissue compared with native cartilage and could be useful for monitoring the status of cartilage health after surgical intervention.

The purpose of this study was to use MRI to determine if a loss of meniscal intra-substance integrity, as determined by T2* relaxation time, is associated with an increase of Kellgren-Lawrence (KL) grade, and if this was correlated with risk factors for cartilage degeneration, namely meniscal extrusion, contact area and anterior-posterior (AP) displacement.Eleven symptomatic knees with a KL 2 to 4 and 11 control knees with a KL 0 to 1 were studied. A 3 Tesla MRI scanner was used to scan all knees at 15° of flexion. With a 222N compression applied, a 3D SPACE sequence was obtained, followed by a spin echo 3D T2* mapping sequence. Next, an internal tibial torque of 5Nm was added and a second 3D SPACE sequence obtained. The MRI scans were post-processed to evaluate meniscal extrusion, contact area, AP displacement and T2* relaxation time.KL grade was correlated with T2* relaxation time for both the anterior medial meniscus (r=0.79, p0.001) and the posterior lateral meniscus (r=0.55, p=0.009). In addition, T2* relaxation time was found to be correlated with risk factors for cartilage degeneration. The largest increases in meniscal extrusion and decreases in contact area were noted for those with meniscal tears (KL 3 to 4). All patients with KL 3 to 4 indicated evidence of meniscal tears.This suggests that a loss of meniscal integrity, in the form of intra-substance degeneration, is correlated with risk factors for cartilage degeneration.

The purpose of this study was to demonstrate the feasibility of biexponential T1ρ relaxation mapping of human knee cartilage in vivo. A three-dimensional, customized, turbo-flash sequence was used to acquire T1ρ-weighted images from healthy volunteers employing a standard 3-T MRI clinical scanner. A series of T1ρ-weighted images was fitted using monoexponential and biexponential models with two- and four-parametric non-linear approaches, respectively. Non-parametric Kruskal–Wallis and Mann–Whitney U-statistical tests were used to evaluate the regional relaxation and gender differences, respectively, with a level of significance of P = 0.05. Biexponential relaxations were detected in the cartilage of all volunteers. The short and long relaxation components of T1ρ were estimated to be 6.9 and 51.0 ms, respectively. Similarly, the fractions of short and long T1ρ were 37.6% and 62.4%, respectively. The monoexponential relaxation of T1ρ was 32.6 ms. The experiments showed good repeatability with a coefficient of variation (CV) of less than 20%. A biexponential relaxation model showed a better fit than a monoexponential model to the T1ρ relaxation decay in knee cartilage. Biexponential T1ρ components could potentially be used to increase the specificity to detect early osteoarthritis by the measurement of different water compartments and their fractions.

The creatine kinase (CK) reaction plays a critical role in skeletal muscle function, and can be studied non-invasively using phosphorus ((31)P) saturation transfer (ST) techniques. However, due to the low MR sensitivity of the (31)P nucleus, most studies on clinically approved magnetic fields (≤3.0 T) have been performed with coarse resolution and limited tissue coverage. However, such methods are not able to detect spatially resolved metabolic heterogeneities, which may be important in diseases of the skeletal muscle. In this study, our aim was to develop and implement a (31)P-MRI method for mapping the kinetics of the CK reaction, and the unidirectional phosphocreatine (PCr) to adenosine triphosphate (ATP) metabolic fluxes in muscles of the lower leg on a clinical 3.0 T MR scanner. We imaged the lower leg muscles of ten healthy volunteers (total experimental time: 40 min, nominal voxel sizes 0.5 mL), and found statistically significant differences between the kinetics of the CK reaction among muscle groups. Our developed technique may allow in the future the early detection of focal metabolic abnormalities in diseases that affect the function of the skeletal muscle.