Immune isolation-enabled nanoencapsulation of donor T cells: a promising strategy for mitigating GVHD and treating AML in preclinical models.

BACKGROUND: In allogeneic-hematopoietic stem cell transplantation for acute myeloid leukemia (AML), donor T cells combat leukemia through the graft-versus-leukemia (GVL) effect, while they also pose a risk of triggering life-threatening graft-versus-host disease (GVHD) by interacting with recipient cells. The onset of GVHD hinges on the interplay between donor T cells and recipient antigen-presenting cells (APCs), sparking T-cell activation. However, effective methods to balance GVHD and GVL are lacking. METHODS: In our study, we crafted nanocapsules by layering polycationic aminated gelatin and polyanionic alginate onto the surface of T cells, examining potential alterations in their fundamental physiological functions. Subsequently, we established an AML mouse model and treated it with transplantation of bone marrow cells (BMCs) combined with encapsulated T cells to investigate the GVL and anti-GVHD effects of encapsulated T cells. In vitro co-culture was employed to probe the effects of encapsulation on immune synapses, co-stimulatory molecules, and tumor-killing pathways. RESULTS: Transplantation of BMCs combined with donor T cells selectively encapsulated onto AML mice significantly alleviates GVHD symptoms while preserving essential GVL effects. Encapsulated T cells exerted their immunomodulatory effects by impeding the formation of immune synapses with recipient APCs, thereby downregulating co-stimulatory signals such as CD28-CD80, ICOS-ICOSL, and CD40L-CD40. Recipient mice receiving encapsulated T-cell transplantation exhibited a marked increase in donor Ly-5.1-BMC cell numbers, accompanied by unaltered in vivo expression levels of perforin and granzyme B. While transient inhibition of donor T-cell cytotoxicity in the tumor microenvironment was observed in vitro following single-cell nanoencapsulation, subsequent restoration to normal antitumor activity ensued, attributed to selective permeability of encapsulated vesicle shells and material degradation. Moreover, the expression of apoptotic proteins and FAS-FAS ligand pathway at normal levels was still observed in leukemia tumor cells. CONCLUSIONS: Encapsulated donor T cells effectively mitigate GVHD while preserving the GVL effect by minimizing co-stimulatory signaling with APCs through early immune isolation. Subsequent degradation of nanocapsules restores T-cell cytotoxic efficacy against AML cells, mediated by cytotoxic pathways. Using transplant-encapsulated T cells offers a promising strategy to suppress GVHD while preserving the GVL effect.

Percutaneous endocardial septal radiofrequency ablation on syncope in patients with hypertrophic obstructive cardiomyopathy: a short-term safety and efficacy study.

Background: Syncope is a serious consequence in patients with hypertrophic obstructive cardiomyopathy (HOCM). Percutaneous endocardial septal radiofrequency ablation (PESA) has emerged as a promising intervention to alleviate symptoms and enhance the quality of life for HOCM patients. However, little is known about the effects of PESA on syncope in HOCM. The authors aimed to study the effects of PESA on syncope in patients with HOCM. Materials and methods: Nineteen patients with HOCM and syncope were enrolled. The left ventricular outflow tract gradient (LVOTG) of the patients was more than 50 mmHg despite medication. The participants underwent PESA under the guidance of intracardiac echocardiography (ICE) combined with a three-dimensional electrophysiological mapping system. The patients were followed for 3 (3-5.5) months. Results: The mean age of the patients was 54.8±13.7 years. Out of the 19 participants, 7 (37%) were females. During the follow-up, the syncope was completely alleviated in 14 patients (73.7%) or the syncope episodes were reduced greater than or equal to 80% in 16 patients (84.2%). The mean NYHA functional class significantly improved from 2.2±0.7 at baseline to 1.7±0.6 during follow-up (P=0.002). The LVOTG and septal thickness showed a decreasing trend from baseline to follow-up (LVOTG: P=0.083, septal thickness: P=0.086). Conclusion: The authors' investigation provides evidence supporting the effectiveness of PESA in reducing syncope episodes in patients with HOCM.

Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and the production of autoantibodies. Previous studies have indicated an association between high-salt diets (HSD) and an increased risk of RA, yet the underlying mechanisms remain unclear. Macrophage pyroptosis, a pro-inflammatory form of cell death, plays a pivotal role in RA. In this study, we demonstrate that HSD exacerbates the severity of arthritis in collagen-induced arthritis (CIA) mice, correlating with macrophage infiltration and inflammatory lesions. Given the significant alterations observed in macrophages from CIA mice subjected to HSD, we specifically investigate the impact of HSD on macrophage responses in the inflammatory milieu of RA. In our in vitro experiments, pretreatment with NaCl enhances LPS-induced pyroptosis in RAW.264.7 and THP-1 cells through the p38 MAPK/NF-κB signaling pathway. Subsequent experiments reveal that Slc6a12 inhibitors and SGK1 silencing inhibit sodium-induced activation of macrophage pyroptosis and the p38 MAPK/NF-κB signaling pathway, whereas overexpression of the SGK1 gene counteracts the effect of sodium on macrophages. In conclusion, our findings verified that high salt intake promotes the progression of RA and provided a detailed elucidation of the activation of macrophage pyroptosis induced by sodium transportation through the Slc6a12 channel.

The HIF-1/ BNIP3 pathway mediates mitophagy to inhibit the pyroptosis of fibroblast-like synoviocytes in rheumatoid arthritis.

BACKGROUND: Synovial hypoxia, a critical pathological characteristic of rheumatoid arthritis (RA), significantly contributes to synovitis and synovial hyperplasia. In response to hypoxic conditions, fibroblast-like synoviocytes (FLS) undergo adaptive changes involving gene expression modulation, with hypoxia-inducible factors (HIF) playing a pivotal role. The regulation of BCL2/adenovirus e1B 19 kDa protein interacting protein 3 (BNIP3) and nucleotide-binding oligomerization segment-like receptor family 3 (NLRP3) expression has been demonstrated to be regulated by HIF-1. The objective of this study was to examine the molecular mechanism that contributes to the aberrant activation of FLS in response to hypoxia. Specifically, the interaction between BNIP3-mediated mitophagy and NLRP3-mediated pyroptosis was conjointly highlighted. METHODS: The research methodology employed Western blot and immunohistochemistry techniques to identify the occurrence of mitophagy in synovial tissue affected by RA. Additionally, the levels of mitophagy under hypoxic conditions were assessed using Western blot, immunofluorescence, quantitative polymerase chain reaction (qPCR), and CUT&Tag assays. Pyroptosis was observed through electron microscopy, fluorescence microscopy, and Western blot analysis. Furthermore, the quantity of reactive oxygen species (ROS) was measured. The silencing of HIF-1α and BNIP3 was achieved through the transfection of short hairpin RNA (shRNA) into cells. RESULTS: In the present study, a noteworthy increase in the expression of BNIP3 and LC3B was observed in the synovial tissue of patients with RA. Upon exposure to hypoxia, FLS of RA exhibited BNIP3-mediated mitophagy and NLRP3 inflammasome-mediated pyroptosis. It appears that hypoxia regulates the expression of BNIP3 and NLRP3 through the transcription factor HIF-1. Additionally, the activation of mitophagy has been observed to effectively inhibit hypoxia-induced pyroptosis by reducing the intracellular levels of ROS. CONCLUSION: In summary, the activation of FLS in RA patients under hypoxic conditions involves both BNIP3-mediated mitophagy and NLRP3 inflammasome-mediated pyroptosis. Additionally, mitophagy can suppress hypoxia-induced FLS pyroptosis by eliminating ROS and inhibiting the HIF-1α/NLRP3 pathway.

Avoiding Unnecessary Systematic Biopsy in Clinically Significant Prostate Cancer: Comparison Between MRI-Based Radiomics Model and PI-RADS Category.

BACKGROUND: MRI-targeted biopsy (MRTB) improves the clinically significant prostate cancer (csPCa) detection rate with fewer biopsy cores in men with suspected PCa. However, whether concurrent systematic biopsy (SB) can be avoided in patients undergoing MRTB remains unclear. PURPOSE: To evaluate the potential value of MRI-based radiomics models in avoiding unnecessary SB in biopsy-naïve patients. STUDY TYPE: Retrospective. POPULATION: A total of 226 patients (mean age 66.6 ± 9.02 years) with suspicion of PCa (PI-RADS score ≥ 3) and received combined cognitive MRTB with SB were retrospectively recruited and randomly divided into training (N = 180) and test (N = 46) cohorts at an 8:2 ratio. FIELD STRENGTH/SEQUENCE: A 3.0 T, biparametric MRI (bpMRI) including T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) map. ASSESSMENT: The whole prostate gland (PG) and the index lesion (IL) were delineated. Three radiomics models of bpMRIPG , bpMRIIL , and bpMRIPG+IL were constructed, respectively, and the performance of each radiomics model was compared with that of PI-RADS assessment. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) regression method was used to select texture features. The area under the curve (AUC) and decision curve analysis were used to estimate the models. RESULTS: The bpMRIPG+IL radiomics model exhibited good discrimination, calibration, and net benefits, which would reduce the SB biopsy in 71.2% and 71.4% of men with PI-RADS ≥ 5 lesions in the training and test cohorts, respectively. DATA CONCLUSION: A bpMRIPG+IL radiomics model may outperform PI-RADS category in help reducing unnecessary SB in biopsy-naïve patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 6.

Machine learning-based combined nomogram for predicting the risk of pulmonary invasive fungal infection in severely immunocompromised patients.

Background: Early and accurate diagnosis of invasive fungal infection (IFI) is pivotal for the initiation of effective antifungal therapy for patients with hematologic malignancies. Methods: This retrospective study involved 235 patients with hematologic malignancies and pulmonary infections diagnosed as IFIs (n=118) or bacterial pneumonia (n=117). Patients were randomly divided into training (n=188) and validation (n=47) datasets. Four feature selection methods with nine classifiers were implemented to select the optimal machine learning (ML) model using five-fold cross-validation. A radiomic signature was constructed using a linear ML algorithm, and a radiomic score (Radscore) was calculated. The combined model was developed with the Radscore, the significant clinical and radiologic factors were selected using multivariable logistic regression, and the results were presented as a clinical radiomic nomogram. A prospective pilot study was also conducted to compare the classification performance of the combined nomogram with practicing radiologists. Results: Significant differences were found in the Radscore between IFI and bacterial pneumonia patients in the training (0.683 vs. -0.724, P<0.001) and validation set (0.353 vs. -0.717, P=0.002). The combined model showed good discrimination performance in the validation cohort [area under the curve (AUC) =0.844] and outperformed the clinical (AUC =0.696) and radiomics (AUC =0.767) model alone (both P<0.05). Conclusions: The clinical radiomic nomogram can serve as a promising predictive tool for IFI in patients with hematologic malignancies.

[Research on real-time detection system of catheter delivering force in vascular interventional robots].

In existing vascular interventional surgical robots, it is difficult to accurately detect the delivery force of the catheter/guidewire at the slave side. Aiming to solve this problem, a real-time force detection system was designed for vascular interventional surgical (VIS) robots based on catheter push force. Firstly, the transfer process of catheter operating forces in the slave end of the interventional robot was analyzed and modeled, and the design principle of the catheter operating force detection system was obtained. Secondly, based on the principle of stress and strain, a torque sensor was designed and integrated into the internal transmission shaft of the slave end of the interventional robot, and a data acquisition and processing system was established. Thirdly, an ATI high-precision torque sensor was used to build the experimental platform, and the designed sensor was tested and calibrated. Finally, sensor test experiments under ideal static/dynamic conditions and simulated catheter delivery tests based on actual human computed tomography (CT) data and vascular model were carried out. The results showed that the average relative detection error of the designed sensor system was 1.26% under ideal static conditions and 1.38% under ideal dynamic stability conditions. The system can detect on-line catheter operation force at high precision, which is of great significance towards improving patient safety in interventional robotic surgery.

Diagnostic Performance of 2D and 3D T2WI-Based Radiomics Features With Machine Learning Algorithms to Distinguish Solid Solitary Pulmonary Lesion.

OBJECTIVE: To evaluate the performance of 2D and 3D radiomics features with different machine learning approaches to classify SPLs based on magnetic resonance(MR) T2 weighted imaging (T2WI). MATERIAL AND METHODS: A total of 132 patients with pathologically confirmed SPLs were examined and randomly divided into training (n = 92) and test datasets (n = 40). A total of 1692 3D and 1231 2D radiomics features per patient were extracted. Both radiomics features and clinical data were evaluated. A total of 1260 classification models, comprising 3 normalization methods, 2 dimension reduction algorithms, 3 feature selection methods, and 10 classifiers with 7 different feature numbers (confined to 3-9), were compared. The ten-fold cross-validation on the training dataset was applied to choose the candidate final model. The area under the receiver operating characteristic curve (AUC), precision-recall plot, and Matthews Correlation Coefficient were used to evaluate the performance of machine learning approaches. RESULTS: The 3D features were significantly superior to 2D features, showing much more machine learning combinations with AUC greater than 0.7 in both validation and test groups (129 vs. 11). The feature selection method Analysis of Variance(ANOVA), Recursive Feature Elimination(RFE) and the classifier Logistic Regression(LR), Linear Discriminant Analysis(LDA), Support Vector Machine(SVM), Gaussian Process(GP) had relatively better performance. The best performance of 3D radiomics features in the test dataset (AUC = 0.824, AUC-PR = 0.927, MCC = 0.514) was higher than that of 2D features (AUC = 0.740, AUC-PR = 0.846, MCC = 0.404). The joint 3D and 2D features (AUC=0.813, AUC-PR = 0.926, MCC = 0.563) showed similar results as 3D features. Incorporating clinical features with 3D and 2D radiomics features slightly improved the AUC to 0.836 (AUC-PR = 0.918, MCC = 0.620) and 0.780 (AUC-PR = 0.900, MCC = 0.574), respectively. CONCLUSIONS: After algorithm optimization, 2D feature-based radiomics models yield favorable results in differentiating malignant and benign SPLs, but 3D features are still preferred because of the availability of more machine learning algorithmic combinations with better performance. Feature selection methods ANOVA and RFE, and classifier LR, LDA, SVM and GP are more likely to demonstrate better diagnostic performance for 3D features in the current study.

IgD promotes pannus formation by activating Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in FLS of CIA rats and the regulation of IgD-Fc-Ig fusion protein.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation, synovial hyperplasia, cartilage degeneration, bone erosion, and pannus. Immunoglobulin D (IgD) plays an important role in autoimmune diseases although the content of it in vivo is low. Increased concentrations of anti-IgD autoantibodies have been detected in many RA patients. IgD-Fc-Ig fusion protein is constructed by connecting human IgD Fc domain and IgG1 Fc domain, which specifically block the IgD/ IgDR pathway and regulate the function of cells expressing IgDR to treat RA. The expression levels of Wnt5A and Frizzled 5 are higher in RA synovial tissue specimens. The complex of Wnt5A-Fzd5-LRP5/6-CTHRC1 promotes the expression of hypoxia inducible factor-1α by activating nuclear factor kappa-B (NF-κB), leading to high expression of VEGF and participating in angiogenesis. VEGF is the strongest angiogenic factor found so far. Here, we aimed to explore whether IgD participates in synovitis by binding to IgDR and regulating the activation of Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in fibroblast synovial cells (FLSs), whether IgD-Fc-Ig fusion protein inhibits VEGF production in FLS of CIA and explore mechanism. We found that IgDR is expressed on MH7A and FLS. IgD promotes VEGF expression by activating Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in MH7A and FLS. After activation of Fzd5 with Wnt5A, IgD-Fc-Ig reduced VEGF-A level in the culture supernatant of MH7A stimulation by IgD. The expressions of CTHRC1, Fzd5, p-P65 and VEGF in MH7A and FLSs were down-regulated after IgD-Fc-Ig treatment. IgD-Fc-Ig suppressed the combination of CTHRC1 and Fzd5 as well. By using the animal model, we demonstrated that IgD-Fc-Ig suppress ankle CTHRC1 and Fzd5 production resulted in inhibition of index of joint inflammation of CIA rats, which were consistent with vitro results. Conclusively, IgD-Fc-Ig inhibits IgD and Wnt5A-induced angiogenesis and joint inflammation by suppressing the combination of CTHRC1 and Fzd5. Our results show that IgD-Fc-Ig exerts its suppressive effect on IgD and Wnt5A by Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway.

Characteristics of COVID-19 patients with preexisting CKD history.

PURPOSE: This paper was intended to describe the characteristics of coronavirus disease 2019 (COVID-19) patients with known chronic kidney disease (CKD) history. METHODS: Clinical information of 20 COVID-19 pneumonia patients with CKD history diagnosed between January 20th and March 1st, 2020 were collected in Tongji Hospital, Wuhan. We listed the clinical baseline data, laboratory findings, chest computed tomography (CT) changes and processed a short period of follow-up of these 20 patients. RESULTS: Based on the estimated glomerular filtration rate (eGFR) on admission, 6 patients were classified as stage 2 of CKD, 5 were as 3a, 2 were as 3b, 3 were as 4 and 4 were as 5, respectively. COVID-19 patients with CKD history were elder and hypertension was the most common comorbidity. Cough and fever accounted for more than 80% of the infectious cases. Lymphopenia, increased D-dimer and elevated infectious indications such as hypersensitive C response protein (hsCRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were also common among these patients. Ground-glass opacity (GGO) and consolidation were the major manifestations in CT scans. 4 patients died and 7 patients underwent acute kidney injury (AKI) during observation. Among 16 discharged patients, 12 were with stable renal function and 4 had deteriorating renal function compared with that of admission. CONCLUSION: Compared to general population infected with SARS-CoV-2, COVID-19 patients with CKD history had a preference to develop to severity with higher fatality rate.

Cycle-Consistent Generative Adversarial Network: Effect on Radiation Dose Reduction and Image Quality Improvement in Ultralow-Dose CT for Evaluation of Pulmonary Tuberculosis.

OBJECTIVE: To investigate the image quality of ultralow-dose CT (ULDCT) of the chest reconstructed using a cycle-consistent generative adversarial network (CycleGAN)-based deep learning method in the evaluation of pulmonary tuberculosis. MATERIALS AND METHODS: Between June 2019 and November 2019, 103 patients (mean age, 40.8 ± 13.6 years; 61 men and 42 women) with pulmonary tuberculosis were prospectively enrolled to undergo standard-dose CT (120 kVp with automated exposure control), followed immediately by ULDCT (80 kVp and 10 mAs). The images of the two successive scans were used to train the CycleGAN framework for image-to-image translation. The denoising efficacy of the CycleGAN algorithm was compared with that of hybrid and model-based iterative reconstruction. Repeated-measures analysis of variance and Wilcoxon signed-rank test were performed to compare the objective measurements and the subjective image quality scores, respectively. RESULTS: With the optimized CycleGAN denoising model, using the ULDCT images as input, the peak signal-to-noise ratio and structural similarity index improved by 2.0 dB and 0.21, respectively. The CycleGAN-generated denoised ULDCT images typically provided satisfactory image quality for optimal visibility of anatomic structures and pathological findings, with a lower level of image noise (mean ± standard deviation [SD], 19.5 ± 3.0 Hounsfield unit [HU]) than that of the hybrid (66.3 ± 10.5 HU, p < 0.001) and a similar noise level to model-based iterative reconstruction (19.6 ± 2.6 HU, p > 0.908). The CycleGAN-generated images showed the highest contrast-to-noise ratios for the pulmonary lesions, followed by the model-based and hybrid iterative reconstruction. The mean effective radiation dose of ULDCT was 0.12 mSv with a mean 93.9% reduction compared to standard-dose CT. CONCLUSION: The optimized CycleGAN technique may allow the synthesis of diagnostically acceptable images from ULDCT of the chest for the evaluation of pulmonary tuberculosis.

Automatic Prediction of MGMT Status in Glioblastoma via Deep Learning-Based MR Image Analysis.

Methylation of the O6-methylguanine methyltransferase (MGMT) gene promoter is correlated with the effectiveness of the current standard of care in glioblastoma patients. In this study, a deep learning pipeline is designed for automatic prediction of MGMT status in 87 glioblastoma patients with contrast-enhanced T1W images and 66 with fluid-attenuated inversion recovery(FLAIR) images. The end-to-end pipeline completes both tumor segmentation and status classification. The better tumor segmentation performance comes from FLAIR images (Dice score, 0.897 ± 0.007) compared to contrast-enhanced T1WI (Dice score, 0.828 ± 0.108), and the better status prediction is also from the FLAIR images (accuracy, 0.827 ± 0.056; recall, 0.852 ± 0.080; precision, 0.821 ± 0.022; and F 1 score, 0.836 ± 0.072). This proposed pipeline not only saves the time in tumor annotation and avoids interrater variability in glioma segmentation but also achieves good prediction of MGMT methylation status. It would help find molecular biomarkers from routine medical images and further facilitate treatment planning.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging of Lung Cancer: Comparison Between Turbo Spin-Echo and Echo-Planar Imaging.

OBJECTIVE: The aim of the study was to compare intravoxel incoherent motion diffusion-weighted imaging (DWI) for evaluating lung cancer using single-shot turbo spin-echo (TSE) and single-shot echo-planar imaging (EPI) in a 3T MR system. METHODS: Both single-shot TSE-DWI and single-shot EPI-DWI were scanned twice respectively for 15 patients with lung cancer. Distortion ratio, signal-to-noise ratio, and contrast-to-noise ratio were compared between the 2 techniques. The Bland-Altman analysis was performed to analyze reproducibility between the parameters of TSE-DWI and EPI-DWI. Short-term test-retest repeatability, as well as interobserver agreement, was evaluated using the coefficient of variation (CV) and the intraclass correlation coefficient (ICC). RESULT: Turbo spin-echo DWI has lower signal-to-noise ratio and similar contrast-to-noise ratio compared with EPI-DWI. Distortion ratio of TSE-DWI was significantly smaller than that of EPI-DWI. The apparent diffusion coefficient (ADC) and true diffusivity (D) of TSE-DWI showed higher values than those of EPI-DWI. The Bland-Altman analysis showed unacceptable limits of agreement between these 2 sequences. Test-retest repeatability was good for ADC and D of EPI-DWI (CV, 14.11%-16.60% and 17.08%-19.53%) and excellent for ADC and D of TSE-DWI (CV, 4.8%-6.19% and 6.05%-8.71%), but relatively poor for perfusion fraction (f) and pseudo-diffusion coefficient (D*) (CV, 25.95%-27.70% and 56.92%-71.84% for EPI, 23.67%-28.67% and 60.85%-70.17% for TSE). For interobserver agreement, both techniques were good to excellent in ADC and D (The lower limit of 95% confidence interval for ICC was almost all greater than 0.75), whereas D* and f had higher interobserver variabilities with D* of TSE-DWI showing poorest reproducibility (ICC, -0.27 to 0.12). CONCLUSIONS: Lung DWI or IVIM using TSE could provide distortion-free images and improve the test-retest robustness of ADC and D as compared with EPI-DWI; however, it might exert a negative effect on perfusion parameter D*.

Ablation of Gsa impairs renal tubule proliferation after injury via CDK2/cyclin E.

Acute kidney injury has a high global morbidity associated with an increased risk of death and chronic kidney disease. Renal tubular epithelial cell regeneration following injury may be a decisive factor in renal repair or the progression of acute kidney injury to chronic kidney disease, but the underlying mechanism of abnormal renal tubular repair remains unclear. In the present study, we investigated the role of heterotrimeric G stimulatory protein α-subunit (Gsa) in renal tubular epithelial cell regeneration. We generated renal tubule epithelium-specific Gsa knockout (GsaKspKO) mice to show the essential role of Gsa in renal tubular epithelial cell regeneration in two AKI models: acute aristolochic acid nephropathy (AAN) and unilateral ischemia-reperfusion injury (UIRI). GsaKspKO mice developed more severe renal impairment after AAN and UIRI, higher serum creatinine levels, and more substantial tubular necrosis than wild-type mice. More importantly, Gsa inactivation impaired renal tubular epithelial cell proliferation by reducing bromodeoxyuridine+ cell numbers in the AAN model and inhibiting cyclin-dependent kinase 2/cyclin E1 expression in the UIRI model. This reduced proliferation was further supported in vitro with Gsa-targeting siRNA. Downregulation of Gsa inhibited tubular epithelial cell proliferation in HK-2 and mIMCD-3 cells. Furthermore, Gsa downregulation inhibited cyclin-dependent kinase 2/cyclin E1 expression, which was dependent on the Raf-MEK-ERK signaling pathway. In conclusion, Gsa is required for tubular epithelial cell regeneration during kidney repair after AKI. Loss of Gsa impairs renal tubular epithelial cell regeneration by blocking the Raf-MEK-ERK pathway.

Left Ventricular Myocardial Deformation on Cine MR Images: Relationship to Severity of Disease and Prognosis in Light-Chain Amyloidosis.

Purpose To measure left ventricular (LV) myocardial strain with cine magnetic resonance (MR) imaging and a deformable registration algorithm (DRA) and to assess the prognostic value of myocardial strain in patients with light-chain (AL) amyloidosis. Materials and Methods In this prospective study, 78 consecutive patients with AL amyloidosis who underwent contrast material-enhanced cardiac MR imaging were enrolled at West China Hospital. LV myocardial strains and late gadolinium enhancement (LGE) were evaluated. Association between myocardial strain and all-cause mortality was analyzed with the stepwise Cox regression model. Results Global longitudinal strain (GLS) and global circumferential strain (GCS) were significantly lower in the no or nonspecific LGE group compared with the subendocardial LGE and transmural LGE groups (mean GLS, -10% ± 3 [standard deviation] vs -7% ± 3 vs -4% ± 1; P < .001) (mean GCS, -13% ± 3 vs -11% ± 3 vs -7% ± 2; P < .001). GLS and GCS were reduced in patients without clinical cardiac amyloidosis (mean GLS, -13% ± 3 vs -16% ± 2; P = .005) (mean GCS, -16% ± 1 vs -19% ± 2; P = .02). Circumferential and radial strains were impaired in basal segments in accordance with the distribution of LGE. Multivariate Cox analysis revealed that GCS (hazard ratio [HR] = 1.16 per 1% absolute decrease; 95% confidence interval [CI]: 1.03, 1.31; P = .02) and the presence of transmural LGE (HR = 1.75; 95% CI: 1.10, 2.80; P = .02) were independent predictors of all-cause mortality after adjustment for LV ejection fraction, right ventricular ejection fraction, LV mass index, GLS, and global radial strain. Conclusion Strain parameters derived with cine MR imaging-based DRA may be a new noninvasive imaging marker with which to evaluate the extent of cardiac amyloid infiltration and may offer independent prognostic information for all-cause mortality in patients with AL amyloidosis.

Comparison of sodium, potassium, calcium, magnesium, zinc, copper and iron concentrations of elements in 24-h urine and spot urine in hypertensive patients with healthy renal function.

Sodium, potassium, calcium, magnesium, zinc, copper and iron are associated with the sequela of hypertension. The most reliable method for testing those elements is by collecting 24-h urine samples. However, this is cumbersome and collection of spot urine is more convenient in some circumstance. The aim of this study was to compare the concentrations of different elements in 24-h urine and spot urine. METHODS: Data was collected from a sub-study of China Salt Substitute and Stroke Study. 240 participants were recruited randomly from 12 villages in two counties in Ningxia, China. Both spot and 24-h urine specimens were collected from each patient. Routine urine test was conducted, and concentration of elements was measured using microwave digestion and Inductively Coupled Plasma-Optical Emission Spectrometry. Partial correlation analysis and Spearman correlation analysis were used to investigate the concentration of different elements and the relationship between 24- h urine and spot urine. RESULTS: A partial correlation in sodium, potassium, calcium, magnesium and iron was found between paired 24-h urine and spot urine samples except copper and zinc: 0.430, 0.426, 0.550, 0.221 and 0.191 respectively. CONCLUSIONS: Spot urine can replace 24-h urine for estimating some of the elements in hypertensive patients with normal renal function.

Multiparametric MRI in differentiating pulmonary artery sarcoma and pulmonary thromboembolism: a preliminary experience.

PURPOSE: We aimed to define multiparametric magnetic resonance imaging (MRI) findings to differentiate between pulmonary artery sarcoma (PAS) and pulmonary thromboembolism (PTE). METHODS: Eleven patients with suspected PTE were prospectively included to undergo pulmonary MRI before surgery or biopsy. MRI protocol included an unenhanced sequence, diffusion-weighted imaging (DWI, b=800 s/mm2) and a dynamic contrast-enhanced sequence. Morphologic characteristics including distribution, filling defect, and intensity were observed on T1-, T2-, and fat-suppressed T2-weighted imaging, DWI, and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) values were calculated. RESULTS: Six patients were pathologically diagnosed as PAS and the other five as chronic PTE. There were no significant differences in age, gender, presenting symptoms, D-dimer, and N-terminal pro-brain natriuretic peptide between the two groups (P > 0.05). Among MRI findings that were tested for their ability to diagnose PAS, area under the curve (AUC) was significantly higher than 0.5 for main pulmonary artery involvement (AUC, 0.83±0.13; P = 0.011), hyperintensity on fat-suppressed T2-weighted imaging (AUC, 0.82±0.14; P = 0.025), hyperintensity on DWI (AUC, 0.88±0.12; P = 0.002), contrast enhancement (AUC, 0.92±0.10; P < 0.001) and pleural effusion (AUC, 0.82±0.14; P = 0.025). Moreover, grape-like appearance in distal pulmonary artery and cardiac invasion had 100% specificity for diagnosis of PAS. However, ADC value of PAS was not significantly different than that of chronic PTE (U, 12.00; P = 0.584). CONCLUSION: Hyperintense filling defect in main pulmonary artery on fat-suppressed T2-weighted imaging and DWI and contrast enhancement may help to discriminate PAS from PTE.

Respiratory self-gating for free-breathing magnetization transfer MRI of the abdomen.

PURPOSE: Magnetization transfer (MT) MRI can be effective for the diagnosis of a broad range of fibrotic diseases, including liver fibrosis. However, respiratory motion, a major source of artifacts in thoracic and abdominal MR imaging, can obscure important anatomic structures, making diagnosis difficult. In this study, we explored the potential to combine free-breathing (FB) respiratory self-gating (RSG) methods with MT saturation for FB MT ratio (MTR) measurements of abdominal organs. METHODS: A respiratory self-gated multiple-gradient recalled echo sequence with MT presaturation (RSG-MT GRE) was developed and applied in a series of seven normal volunteers. We compared the MTR values of liver, pancreas, kidney, spleen, and posterior paraspinal muscle measured using our RSG-MT GRE sequence and a conventional MT GRE sequence. RESULTS: RSG consistently reduced motion artifacts within MT-weighted images acquired during FB, improved the accuracy of FB MTR measurements, and produced comparable MTRs to breath-holding MTR measurements. CONCLUSION: RSG approaches may offer to improve the utility of MT-weighted imaging methods for the assessment of fibrotic diseases and tumor desmoplasia in abdominal organs.