Cardioprotective effect of NRG-4 gene expression on spontaneous hypertension rats and its mechanism through mediating the activation of ErbB signaling pathway.

To explore the myocardial protective effect of Neuregulin-4 (NRG-4) gene expression on spontaneous hypertension (SHR) rats and its mechanism through mediating the activation of the ErbB signaling pathway, this study was conducted. For this purpose, forty 24-week-old male SPF SHR rats were selected as the experimental group, and 10 age and sex-matched Wistar Kyoto (WKY) rats were selected as the control group. Cardiac tissues were collected for hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, Masson staining, and immunohistochemical staining. Following tail vein injection of recombinant lentiviral vectors, the experimental groups were constructed as the control group (SHR rats without any treatment), Empty vector group (Empty Vector transfection), shRNA negative control (NC) group (LV-shRNA-NRG-4 NC transfection to silence the expression of NRG-4), shRNA group (LV-shRNA-NRG-4 transfection), pcDNA3.1(-) NC group (pcDNA3.1(-)-NRG-4 empty vector transfection) and pcDNA3.1(-) group (pcDNA3.1(-)-NRG-4 transfection to overexpress NRG-4). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression levels In addition, methyl thiazolyl tetrazolium salt (MTT) assay and flow cytometry were performed to detect the proliferation and apoptosis of cardiomyocytes, respectively. Results showed that in the SHR group, the cardiomyocytes showed hypertrophy, disordered arrangement, hyperchromatic nucleus, irregular shape, obvious rupture of myocardial fibers, and obvious proliferation of fibrous stroma; obvious myocardial fibrosis, and there were more blue collagen fibers around cardiomyocytes and myocardial arterioles; cardiomyocytes were swollen, muscle fibers arranged disorderly, collagen around the coronary artery and myocardial interstitium increased significantly with a cross-linking appearance; besides, compared with WKY group, the apoptosis index of cardiomyocytes in SHR group was significantly increased (P<0.05). The expression of NRG-4 protein was decreased in the SHR group compared with the WKY group (P<0.05). In vitro, there was no difference in the mRNA expression of NRG-4, ErbB2 and ErbB4, MMP2, TGFß1 and α-SMA, as well as Caspase3, Bax and Bcl-2 among the control group, Empty vector group, shRNA NC group and pcDNA3.1(-) NC group (P>0.05). While shRNA group showed decreased expressions of NRG-4, ErbB2, ErbB4, MMP2, TGFß1, α-SMA and Bcl-2, while increased Caspase3 and Bax expressions, as well as promoted cell proliferation and cell apoptosis when compared with the shRNA NC group (P<0.05); while compared with pcDNA3.1(-) NC group, pcDNA3.1(-) group had highly increased expressions of NRG-4, ErbB2, ErbB4, MMP2, TGFß1, α-SMA and Bcl-2, while decreased Caspase3 and Bax expressions, inhibited cell proliferation and cell apoptosis (all P<0.05). It is concluded Upregulation of NRG-4 gene expression can promote the activation of the ErbB signaling pathway, thus inhibiting the proliferation and apoptosis of cardiomyocytes in SHR rats, reversing myocardial fibrosis, and playing its cardioprotective role.

Prospective comparison between DCE-MRR and 99m Tc-DTPA-based SPECT for determination of allograft renal function.

BACKGROUND: Glomerular filtration rate (GFR) is a preferred indicator of allograft renal function, but direct measurement of GFR remains complicated. PURPOSE: To prospectively compare dynamic contrast-enhanced MR renography (DCE-MRR) with 99m Tc-DTPA-based single-photon emission computed tomography (SPECT) for determination of allograft renal function. STUDY TYPE: Prospective. POPULATION: Seventy kidney-transplant recipients FIELD STRENGTH: A low-dose DCE-MRR with a 3.0T scanner and a 99m Tc-DTPA-based SPECT after renal transplantation were performed. ASSESSMENT: A Baumann-Rudin (BR) and a modified two-compartment model (JZ2C) were used for DCE-MRR analysis. Standard Gate's method was used for SPECT analysis. An endogenous creatinine clearance rate (CCr) constituted the reference standard. STATISTICAL TESTS: Pearson correlation test and Bland-Altman agreement analysis. RESULTS: The reference CCr-GFR was 59.58 ± 23.72 mL/min/1.73 m2 . GFR determined by eGFR, BR, JZ2C, and SPECT was 90.22 ± 34.38, 36.78 ± 14.46, 48.99 ± 23.88, and 67.32 ± 18.44 mL/min/1.73 m2 , respectively. DCE-MRR using JZ2C had the best overall performance, with a Pearson correlation coefficient of 0.81, a bias of -10.58 mL/min/1.73 m2 , and a precision of 14.61 mL/min/1.73 m2 , as well as high accuracy (30-50% intervals: 74.3-90.0%). Although SPECT had a small bias (7.74 mL/min/1.73 m2 ), it had a poor correlation coefficient (0.38), poor precision (23.93 mL/min/1.73 m2 ), and low accuracy (64.3-72.3%) as compared with DCE-MRR using JZ2C. DATA CONCLUSION: DCE-MRR using JZ2C is superior to 99m Tc-DTPA-based SPECT to determine allograft renal function. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:262-269.

Renal cortex blood perfusion contrast-enhanced ultrasound: Assisting diagnosis and treatment of renal artery disease.

Renal cortical blood perfusion CEUS can evaluate the structure and microcirculation of renal cortex, which is expected to provide a safer and more convenient evaluation system for clinicians in the diagnosis and treatment of early renal artery disease.

Transcriptome profiling of abdominal aortic tissues reveals alterations in mRNAs of Takayasu arteritis.

Takayasu arteritis (TA) is a chronic granulomatous vasculitis involving in the main branches of aorta. Previous studies mainly used peripheral blood and some vascular tissues but seldom studies have sequenced vascular tissues. Here in this study, we aimed to explore the alterations of mRNA in TA by performing bulk RNA sequencing. A total of 14 abdominal aortic tissues including 8 from renal transplantation and 6 from patient with TA undergoing bypass surgeries. Bulk RNA sequencing were performed and after the quality control, a total of 1897 transcripts were observed to be significantly differently (p < 0.05 and Log2FC > 1) expressed between the TA and control group, among which 1,361 transcripts were in TA group and 536 in the Control group. Reactome Pathway Enrichment Comparison analysis revealed interleukin-10 signaling and signaling by interleukins were highly expressed in TA group. Besides, extracellular matrix organization was also observed in this group. WGCNA and PPI obtained 26 core genes which were highly correlated with the clinical phenotype. We then also perform deconvolution of the bulk RNA-seq data by using the scRNA-seq dataset and noticed the high proportion of smooth muscle cells in our dataset. Additionally, immunohistochemical staining confirmed our bioinformatic analysis that TA aortic tissues express high levels of IL-1R1 and IL-1R2. Briefly, this study revealed critical roles of interleukins in TA pathogenesis, and SMCs may also participate in the reconstruction in vessel wall at late stage of TA.

Single-Cell RNA Sequencing Revealed CD14+ Monocytes Increased in Patients With Takayasu's Arteritis Requiring Surgical Management.

Objectives: Takayasu Arteritis (TA) is a highly specific vascular inflammation and poses threat to patients' health. Although some patients have accepted medical treatment, their culprit lesions require surgical management (TARSM). This study aimed at dissecting the transcriptomes of peripheral blood mononuclear cells (PBMCs) in these patients and to explore potential clinical markers for TA development and progression. Methods: Peripheral blood were collected from four TA patients requiring surgical management and four age-sex matched healthy donors. Single cell RNA sequencing (scRNA-seq) was adopted to explore the transcriptomic diversity and function of their PBMCs. ELISA, qPCR, and FACS were conducted to validate the results of the analysis. Results: A total of 29918 qualified cells were included for downstream analysis. Nine major cell types were confirmed, including CD14+ monocytes, CD8+ T cells, NK cells, CD4+ T cells, B cells, CD16+ monocytes, megakaryocytes, dendritic cells and plasmacytoid dendritic cells. CD14+ monocytes (50.0 vs. 39.3%, p < 0.05) increased in TA patients, as validated by FACS results. TXNIP, AREG, THBS1, and CD163 increased in TA patients. ILs like IL-6, IL-6STP1, IL-6ST, IL-15, and IL-15RA increased in TA group. Conclusion: Transcriptome heterogeneities of PBMCs in TA patients requiring surgical management were revealed in the present study. In the patients with TA, CD14+ monocytes and gene expressions involved in oxidative stress were increased, indicating a new treatment and research direction in this field.

Laser-jamming effectiveness analysis of combined-fiber lasers for airborne defense systems.

The laser-jamming effectiveness of combined fiber lasers for airborne defense systems is analyzed in detail. Our preliminary experimental results are proof of the concept of getting a high-power laser through a beam combination technique. Based on combined fiber lasers, the jamming effectiveness of four-quadrant guidance and imaging guidance systems are evaluated. The simulation results have proved that for a four-quadrant guidance system, the tracking system takes only two seconds to complete tracking, and the new tracking target is the jamming laser; for the imaging guidance system, increasing the power of the jamming laser or the distance between the target and the jamming laser are both efficient ways to achieve a successful laser jamming.

Experience on surgical management of rupture of abdominal aortic aneurysm.

OBJECTIVE: To describe our surgical experience on rupture of abdominal aortic aneurysm. METHODS: Two cases of ruptured aortic aneurysms with severe complication were analysed. Aorta reconstruction procedures were performed using bifurcated e-PTFE grafts during emergency operation. Diagnosis, preoperative resuscitation, emergency surgical intervention, and postoperative complications of these patients were summarized and discussed. RESULTS: Rupture of aortic aneurysm in both patients presented as a huge retroperitoneum haematoma by computed tomography scan. They were successfully saved by prompt body fluid compensation, emergency procedure, intraoperative resuscitation, and postoperative intensive care. CONCLUSIONS: Correct diagnosis, prompt surgical management, immediate intraoperative proximal aorta clamping during procedure, and effective management of postoperative complications were the key points to successful treatment of ruptured aortic aneurysm.

Nanoparticle as a new gene transferring vector in specific expression gene.

OBJECTIVE: To evaluate the possibility and efficiency of nanoparticle as a new vector in specific gene transference. METHODS: Nanoparticle-DNA complex was prepared with Poly-dl-lactic-co-glycolic acid (PLGA) bearing anti-sense monocyte chemotactic protein-1 (A-MCP-1), a specific expression gene, and the package efficiency, release progress in vitro, and the size of the complex were determined. The possibility of the new vector was evaluated with genomic DNA PCR by transferring gene into cultured smooth muscle cells (SMC), cationic lipids as a control. For study in vivo, jugular vein-to-artery bypass grafting procedures were performed on 20 New Zealand white rabbits, of which 6 grafts were transferred with nanoparticle-A-MCP-1 (200 microg), 6 with A-MCP-1 (200 microg) by cationic liposome, 4 with LNCX plasmid, and 4 as control. Fourteen days after the grafts were harvested, the expression of A-MCP-1 and its effect on MCP-1 in vein grafts were detected by dot blot, and the morphologic evaluation of grafts was performed. RESULTS: The package efficiency of the nanoparticle-DNA complex was 0.9%, release progress in vitro lasted 2 weeks, and the size ranged from 150 to 300 nm. SMC genomic DNA PCR showed that A-MCP-1 gene could be successfully transfected into cells by nanoparticle. The study in vivo indicated that A-MCP-1 mRNA was expressed in both local gene delivery groups, nanoparticle and liposome, meanwhile, MCP-1 expression in vein grafts was significantly inhibited and neointimal hyperplasia was notably reduced. CONCLUSION: Nanoparticle can act as a vector to transfect specific gene.