Maternal exposure to hyperbaric oxygen at the preimplantation stages increases apoptosis and ectopic Cdx2 expression and decreases Oct4 expression in mouse blastocysts via Nrf2-Notch1 upregulation and Nf2 downregulation.

BACKGROUND: The environmental oxygen tension has been reported to impact the blastocyst quality and cell numbers in the inner cell mass (ICM) during human and murine embryogenesis. While the molecular mechanisms leading to increased ICM cell numbers and pluripotency gene expression under hypoxia have been deciphered, it remains unknown which regulatory pathways caused the underweight fetal body and overweight placenta after maternal exposure to hyperbaric oxygen (HBO). RESULTS: The blastocysts from the HBO-exposed pregnant mice revealed significantly increased signals of reactive oxygen species (ROS) and nuclear Nrf2 staining, decreased Nf2 and Oct4 expression, increased nuclear Tp53bp1 and active caspase-3 staining, and ectopic nuclear signals of Cdx2, Yap, and the Notch1 intracellular domain (N1ICD) in the ICM. In the ICM of the HBO-exposed blastocysts, both Nf2 cDNA microinjection and Nrf2 shRNA microinjection significantly decreased the ectopic nuclear expression of Cdx2, Tp53bp1, and Yap whereas increased Oct4 expression, while Nrf2 shRNA microinjection also significantly decreased Notch1 mRNA levels and nuclear expression of N1ICD and active caspase-3. CONCLUSION: We show for the first time that maternal exposure to HBO at the preimplantation stage induces apoptosis and impairs ICM cell specification via upregulating Nrf2-Notch1-Cdx2 expression and downregulating Nf2-Oct4 expression.

Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents a global threat, and the interaction between the virus and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. However, the mechanisms underpinning ACE2-mediated viral entry across species remains unclear. Using infection assay, we evaluated SARS-CoV-2 entry mediated by ACE2 of 11 different animal species. We discovered that ACE2 of Rhinolophus sinicus (Chinese rufous horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (wild pig), Capra hircus (goat), and Manis javanica (Malayan pangolin) facilitated SARS-CoV-2 entry into nonsusceptible cells. Moreover, ACE2 of the pangolin also mediated SARS-CoV-2 entry, adding credence to the hypothesis that SARS-CoV-2 may have originated from pangolins. However, the ACE2 proteins of Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (red junglefowl), Notechis scutatus (mainland tiger snake), or Mus musculus (house mouse) did not facilitate SARS-CoV-2 entry. In addition, a natural isoform of the ACE2 protein of Macaca mulatta (rhesus monkey) with the Y217N mutation was resistant to SARS-CoV-2 infection, highlighting the possible impact of this ACE2 mutation on SARS-CoV-2 studies in rhesus monkeys. We further demonstrated that the Y217 residue of ACE2 is a critical determinant for the ability of ACE2 to mediate SARS-CoV-2 entry. Overall, these results clarify that SARS-CoV-2 can use the ACE2 receptors of multiple animal species and show that tracking the natural reservoirs and intermediate hosts of SARS-CoV-2 is complex.

Pseudolaric Acid B Attenuates High Salt Intake-Induced Hypertensive Left Ventricular Remodeling by Modulating Monocyte/Macrophage Phenotypes.

BACKGROUND Studies in ApoE knockout mice have shown that pseudolaric acid B (PB) can act as an immunomodulatory drug and attenuate atherosclerosis progression by modulating monocyte/macrophage phenotypes. Our previous study demonstrated that high salt intake could shift the phenotype of monocytes/macrophages to an inflammatory phenotype, and that this shift was related to hypertension and hypertensive left ventricular (LV) remodeling. However, no comprehensive assessment of the effects of PB on hypertensive LV remodeling has been conducted. MATERIAL AND METHODS In this study, RAW264.7 macrophages cultured with different concentrations of NaCl were used to investigate the modulating effects of PB on macrophage phenotype. Furthermore, N-nitro-L-arginine methyl ester hypertensive mice were used to investigate the modulating effects of PB on monocyte phenotype. LV remodeling was investigated by echocardiography. LV morphologic staining (for cardiomyocyte hypertrophy and collagen deposition) was performed at the time of sacrifice. RESULTS The results showed that PB significantly improved the viability of RAW264.7 cells, suppressed their phagocytic and migration abilities, and inhibited their phenotypic shift to M1 macrophages. In addition, the blood pressure of PB-treated mice was significantly decreased relative to that of control mice. Furthermore, after PB treatment, the percentage of Ly6Chi monocytes was significantly decreased while that of Ly6Clo monocytes was apparently increased. Moreover, PB preserved LV function and alleviated myocardial fibrosis and cardiomyocyte hypertrophy as measured at the end of the experimental period. The transfer of monocytes from PB-treated mice to hypertensive mice achieved the same effects. CONCLUSIONS Together, these findings indicate that PB exerts its protective effects on hypertensive LV remodeling by modulating monocyte/macrophage phenotypes and warrants further investigation.

Retraction Note: Prognostic value of heart failure in hemodialysis-dependent end-stage renal disease patients with myocardial fibrosis quantification by extracellular volume on cardiac magnetic resonance imaging.

An amendment to this paper has been published and can be accessed via the original article.

Prognostic value of heart failure in hemodialysis-dependent end-stage renal disease patients with myocardial fibrosis quantification by extracellular volume on cardiac magnetic resonance imaging.

BACKGROUND: End-stage renal disease (ESRD) patients are at high cardiovascular risk, and myocardial fibrosis (MF) accounts for most of their cardiac events. The purpose of this study is to investigate the prognostic value and risk stratification of MF as measured by extracellular volume (ECV) on cardiac magnetic resonance (CMR) for heart failure (HF) in patients with hemodialysis-dependent ESRD. METHODS: Sixty-six hemodialysis ESRD patients and 25 matched healthy volunteers were prospectively enrolled and underwent CMR to quantify multiple parameters of MF by T1 mapping and late gadolinium enhancement (LGE). All ESRD patients were followed up for 11-30 months, and the end-point met the 2016 ESC guidelines for the definition of HF. RESULTS: Over a median follow-up of 18 months (range 11-30 months), there were 26 (39.39%) guideline-diagnosed HF patients in the entire cohort of ESRD subjects. The native T1 value was elongated, and ECV was enlarged in the HF cohort relative to the non-HF cohort and normal controls (native T1, 1360.10 ± 50.14 ms, 1319.39 ± 55.44 ms and 1276.35 ± 56.56 ms; ECV, 35.42 ± 4.42%, 31.85 ± 3.01% and 26.97 ± 1.87%; all p<0.05). In the cardiac strain analysis, ECV was significantly correlated with global radial strain (GRS) (r = - 0.501, p = 0.009), global circumferential strain (GCS) (r = 0.553, p = 0.005) and global longitudinal strain (GLS) (r = 0.507, p = 0.008) in ESRD patients with HF. Cox proportional hazard regression models revealed that ECV (hazard ratio [HR] = 1.160, 95% confidence interval: 1.022 to 1.318, p = 0.022) was the only independent predictor of HF in ESRD patients. It also had a higher diagnostic accuracy for detecting MF (area under the curve [AUC] = 0.936; 95% confidence interval: 0.864 to 0.976) than native T1 and post T1 (all p ≤ 0.002). Kaplan-Meier analysis revealed that the high-ECV group had a shorter median overall survival time than the low-ECV group (18 months vs. 20 months, log-rank p = 0.046) and that ESRD patients with high ECV were more likely to have HF. CONCLUSIONS: Myocardial fibrosis quantification by ECV on CMR T1 mapping was shown to be an independent risk factor of heart failure, providing incremental prognostic value and risk stratification for cardiac events in ESRD patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-DND-17012976, 13/12/2017, Retrospectively registered.

Poor cardiovascular health status among Chinese women.

BACKGROUND: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). METHODS: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. RESULTS: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. CONCLUSION: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.

Inhibitory role of lentivirus-mediated aquaporin-4 gene silencing in the formation of glial scar in a rat model of traumatic brain injury.

Traumatic brain injury (TBI), an acute degenerative pathology of the central nervous system, is a leading cause of death and disability. As the glial scar is a mechanical barrier to nerve regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Herein, we aim to investigate the effects of aquaporin-4 (AQP4) gene silencing on the glial scar formation after TBI by establishing rat models. After modeling, TBI rats were transfected with AQP4 small hairpin RNA [shRNA] (AQP4 gene silencing by lentiviral vector-delivered shRNA) and empty vectors, respectively. Neurological functions of the rats were evaluated after TBI. The hematoxylin and eosin staining was conducted to observe histomorphological changes in rat brain tissues. The messenger RNA (mRNA) and protein expressions of glial fibrillary acidic protein (GFAP), vimentin, fibronectin, laminin, and AQP4 were measured by reverse transcription-quantitative polymerase chain reaction and Western blot analysis. The ratio of positive expression area was calculated, and the glial scar was observed by immunohistochemistry. At the 7th, 14th, and 28th days after TBI, TBI rats treated with AQP4 shRNA showed improved neurological function and lessened histomorphological changes. AQP4 gene silencing mediated by lentivirus decreased the mRNA and protein expressions of GFAP, vimentin, fibronectin, and laminin, the number of positive cells, the ratio of positive expression area, and the glial scar. Our study demonstrates that lentivirus-mediated AQP4 gene silencing could inhibit the formation of glial scar after TBI, which is beneficial to the recovery of neurological function.

Increased 90-Day Mortality in Spontaneously Breathing Patients With Paraquat Poisoning: In Addition to Disease Severity, Lung Strain May Play a Role.

OBJECTIVES: 1) To evaluate the prognostic roles of quantitative CT and pulmonary function tests and 2) to assess the association of dynamic strain and ventilation heterogeneity during unassisted spontaneous breathing with 90-day survival in patients with paraquat poisoning. DESIGN: Prospective study. SETTING: A university hospital ICU. PATIENTS: One-hundred spontaneously breathing patients with paraquat poisoning without mechanical ventilation. INTERVENTIONS: A standardized treatment protocol. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected to measure the plasma paraquat concentration upon arrival. CT scans at suspended inspiration and pulmonary function tests were performed at day 5. The weight of the poorly aerated lung compartment as a percentage of total lung weight (%Wpoor) was exponentially transformed, generating a new variable, Exp(%Wpoor/15). The functional residual capacity that was determined by helium dilution was used to calculate the dynamic strain (tidal volume/functional residual capacity by helium dilution method). Respiratory system reactance at 5 Hz was used as a marker of ventilation heterogeneity. Exp(%Wpoor/15) (adjusted hazard ratio, 2.58; 95% CI, 2.021-3.296; p < 0.001) was most strongly associated with mortality, such that neither blood paraquat concentration nor PaO2 provided any additional prognostic information. The ratio of residual volume to total lung capacity as a percentage of the predicted value (adjusted hazard ratio, 1.041; 95% CI, 1.026-1.057; p < 0.001) was the only variable that added prognostic value to Exp(%Wpoor/15). While controlling for Exp(%Wpoor/15) and percentage of predicted residual volume/total lung capacity, increases in dynamic strain (adjusted hazard ratio, 2.041/0.1 U; 95% CI, 1.283-3.248; p = 0.003) and/or decreases in respiratory system reactance at 5 Hz (adjusted hazard ratio, 1.19/0.1 U; 95% CI, 1.03-1.386; p = 0.02) were independently associated with increased 90-day mortality. CONCLUSIONS: In patients with paraquat poisoning, Exp(%Wpoor/15) and percentage of residual volume/total lung capacity are independent prognostic indicators. Higher dynamic strain and increased ventilation heterogeneity during unassisted spontaneous breathing were associated with worsened survival independent of Exp(%Wpoor/15) and percentage of residual volume/total lung capacity.

The Dynamics of Circulating Monocyte Subsets and Intra-Plaque Proliferating Macrophages during the Development of Atherosclerosis in ApoE-/- Mice.

To detect the development of monocytes and proliferative macrophages in atherosclerosis of ApoE-/- mice, we randomly assigned 84 ApoE-/- mice fed western diet or chow diet. On weeks 2, 4, 6, 8, 10, and 12 after fed high-fat diet or normal chow diet, animals were euthanized (n = 7 for each group at each time point). Flow cytometry methods were used to analyze the proportions of circulation monocyte subsets. The macrophage and proliferative macrophage accumulation within atherosclerotic plaques was estimated by confocal florescence microscopy. Plasma levels of total cholesterol and triglyceride were measured by ELISA kit. The plaques of aortic sinus were stained with Oil Red O. The percent of Ly6Chi circulation monocyte, the density of proliferation macrophage, the total plasma cholesterol and triglyceride levels, the lesion area of ApoE-/- mice were consistently elevated in chow diet throughout the trial. The total plasma cholesterol and triglyceride levels, the lesion area were elevated in western diet group with age, and they were always higher than the chow diet group. The Ly6Chi monocytes and proliferative macrophages reached a plateau at 8 weeks and 6 weeks; despite continued high-triglyceride high-cholesterol diet the percent did not significantly change. Interestingly, the density of macrophage did not change significantly over age in western and chow diet groups. Our results provide a dynamic view of Ly6Chi monocyte subset, the density of macrophage and proliferation macrophage change during the development and progression of atherosclerosis, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.

Predictive Value of Four-Dimensional Strain Echocardiography for Adverse Cardiovascular Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Primary Percutaneous Coronary Intervention.

OBJECTIVES: To investigate the predictive value of four-dimensional (4D) strain echocardiography for major adverse cardiovascular events (MACE) in ST-elevation acute myocardial infarction (STEMI) patients. METHODS: Consecutive STEMI patients who underwent successful primary coronary interven tion (PCI) were enrolled and followed, with 2D and 4D strain echocardiography performed within 1 week after PCI. RESULTS: Twenty-six first MACE were recorded in 81 patients who finished a ∼3.0 year follow-up. Compared with those without MACE, subjects with MACE were more likely to have anterior MI (73.08 vs. 38.18%, p = 0.003), significantly decreased 2D left ventricular ejection fraction (2DLVEF) and 4DLVEF (all p < 0.05), as well as an overtly compromised 4D strain parameters. The prediction models incorporating infarct location with either 2DLVEF or 4D strain parameters were then developed. Model comparisons revealed that the global area strain (GAS)-based model had the highest discriminative capacity (c statistics = 0.774) and was well calibrated for MACE. Additionally, the clinical utility of the GAS-based prediction model was verified by decision curve analysis showing a consistent positive and larger net benefit compared to the 2DLVEF-based model. CONCLUSIONS: Our data support a superiority of 4D strain echocardiography over conventional 2D echocardiography, especially GAS, for risk stratification in STEMI patients after successful primary PCI.

Prediction of Incident Hypertension Within the Next Year: Prospective Study Using Statewide Electronic Health Records and Machine Learning.

BACKGROUND: As a high-prevalence health condition, hypertension is clinically costly, difficult to manage, and often leads to severe and life-threatening diseases such as cardiovascular disease (CVD) and stroke. OBJECTIVE: The aim of this study was to develop and validate prospectively a risk prediction model of incident essential hypertension within the following year. METHODS: Data from individual patient electronic health records (EHRs) were extracted from the Maine Health Information Exchange network. Retrospective (N=823,627, calendar year 2013) and prospective (N=680,810, calendar year 2014) cohorts were formed. A machine learning algorithm, XGBoost, was adopted in the process of feature selection and model building. It generated an ensemble of classification trees and assigned a final predictive risk score to each individual. RESULTS: The 1-year incident hypertension risk model attained areas under the curve (AUCs) of 0.917 and 0.870 in the retrospective and prospective cohorts, respectively. Risk scores were calculated and stratified into five risk categories, with 4526 out of 381,544 patients (1.19%) in the lowest risk category (score 0-0.05) and 21,050 out of 41,329 patients (50.93%) in the highest risk category (score 0.4-1) receiving a diagnosis of incident hypertension in the following 1 year. Type 2 diabetes, lipid disorders, CVDs, mental illness, clinical utilization indicators, and socioeconomic determinants were recognized as driving or associated features of incident essential hypertension. The very high risk population mainly comprised elderly (age>50 years) individuals with multiple chronic conditions, especially those receiving medications for mental disorders. Disparities were also found in social determinants, including some community-level factors associated with higher risk and others that were protective against hypertension. CONCLUSIONS: With statewide EHR datasets, our study prospectively validated an accurate 1-year risk prediction model for incident essential hypertension. Our real-time predictive analytic model has been deployed in the state of Maine, providing implications in interventions for hypertension and related diseases and hopefully enhancing hypertension care.

[Research advances in the regulation of cardiovascular metabolic disorders and its related risk factors by C1q/TNF related proteins].

The complement C1q/TNF related protein (CTRP) family is rapidly growing and currently comprises 15 members. Although CTRP proteins share a common structure composed of four distinct domains: a signal peptide at the N terminus, a short variable region, a collagenous domain, and a C-terminal globular domain, which is homologous to adiponectin, each CTRP has a unique tissue expression profile and varied function. In this review we focus on the biochemistry and pleiotropic functions of CTRPs as new molecular mediators regulating cardiovascular metabolic disorders and its related risk factors diseases.

[Application of Low Concentration Contrast Agent Combined Double Low Dose in CT Pulmonary Angiography for Pulmonary Embolism].

OBJECTIVE: To investigate the feasibility of low concentration contrast agent combined double low dose in CT pulmonary angiography. METHODS: 60 patients with clinically suspected pulmonary embolism examed by CT pulmonary angiography (CTPA) were divided into two groups (experimental group: n=30,80 kV, 15 mL,320 mg I/mL;control group: n=30,120 kV,50 mL,370 mg I/mL). The average CT value of main right and left pulmonary arteries,lobar arteries was calculated. Imaging post processing techniques included curved plannar reconstruction (CPR),volume rendering (VR) and maximal intensity projection (MIP). The artifact of the remaining contract in the superior vena cava and overall quality of the image were observed and analyzed by two senior doctors who were double blinded. RESULTS: All patients in two groups completed CTPA successfully. The image qualities of two groupssatisfy clinical diagnostic requirements and no difference of the image qualities was observed between two groups (P>0.05). The evaluation of venous pollution in experimental group was better than that of control group (P<0.01).No difference of CT values were observed between two groups [experimental group (423.2±89.4) HU,control group (465.7±85.6) HU](P>0.05). The SNR and CNR in experimental group were lower than those in control group (P<0.01 both).The CT dose index volume (CTDIvol),dose-length product (DLP) and size-specific dose estimates (SSDE) in experimental group were significantly lower than those incontrol group (P<0.01 all). CONCLUSION: The low concentration contrast agent combined double low dose in CT pulmonary angiography satisfies clinical diagnostic requirements. It has good clinical value for it could reduce venous pollution,iodine contrast agent and radiation exposure.

Diagnostic value of renal perfusion in patients with chronic kidney disease using 3D arterial spin labeling.

PURPOSE: To evaluate the diagnostic value of 3D arterial spin labeling (ASL) for noninvasive quantification of renal blood flow (RBF) in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: CKD patients (n = 27) and healthy volunteers (n = 36) underwent renal 3T ASL magnetic resonance imaging, with inversion times from 1200 to 2000 msec for volunteers in the preliminary test, and 1800 to 2000 msec for volunteers and CKD patients in the formal experiments. The cortical RBFs were compared, and a correlation between RBF and estimated glomerular filtration rate (eGFR) was evaluated. RESULTS: For healthy volunteers, RBF values increased with TIs from 1200 to 1600 msec, but were almost constant at TIs from 1600 to 2000 msec. The cortical RBF values of CKD patients were lower than that of healthy volunteers at TIs from 1800 to 2000 msec. In addition, the CKD patients had lower cortical RBF values than the healthy volunteers (P < 0.01 for both), and their RBF values positively correlated with eGFR. CONCLUSION: 3D ASL is a potential noninvasive method for measuring renal perfusion that can provide valuable information for clinical CKD diagnosis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:589-594.

VEGF-C-mediated cardiac lymphangiogenesis in high salt intake accelerated progression of left ventricular remodeling in spontaneously hypertensive rats.

High salt (HS) diet can accelerate the progress of hypertensive left ventricular (LV) remodeling. But the detailed mechanism remains poorly understood. We hypothesized HS intake could impact cardiac lymphangiogenesis through tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway which might play an important role in HS intake accelerated LV remodeling. Eight-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were randomized to 0.5% NaCl (Low salt, LS) and 8% NaCl (high salt, HS) diets for 12 weeks. LV remodeling was determined by echocardiography. LV invasive hemodynamic analysis and morphologic staining (cardiomyocyte hypertrophy, collagen deposition, TonEBP expression, macrophage infiltration and lymphatic density) were performed at the time of sacrifice. The blood pressure of SHR-HS group was significantly increased compared to SHR-LS and WKY groups. Meanwhile, The LV chamber size was markedly enlargement, LV function apparently compromised accompanied with a severe macrophage infiltration, and fibrosis in the perivascular and interstitium of LV compared with SHR-LS group. Furthermore, the expression levels of VEGF-C, TonEBP, and lymphatic markers in SHR-HS group were significantly increased parallel with apparent lymphangiogenesis compared with SHR-LS group. Our work indicates that TonEBP/VEGF-C signaling pathway was up-regulated in HS intake accelerated hypertensive LV remodeling process that may be valuable for further investigation.

[Clinical Study of Rs-EPI DWI to Improve Imaging Quality and Assessment on Intracranial Mass Lesions].

OBJECTIVES: To explore the clinical value of readout-segmented echo planar imaging (Rs-EPI) sequence in the assessment of intracranial mass lesions compared to the standard single-shot EPI (Ss-EPI) sequence. METHODS: We included 21 patients with intracranial mass lesions who underwent both Ss-EPI diffusion weighted imaging (DWI) and Rs-EPI DWI at 3.0T MR scanner with a twenty-channel head-neck coil. The quality of images was assessed by two experienced radiologists independently. The differences in image quality between two sequences were analyzed using Wilcoxon signed-rank test. Inter-observer agreements were analyzed using interclass correlation coefficient (ICC) and Kappa test. RESULTS: All objectives were completed on 3.0T MR. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in Rs-EPI DWI were higher than those in Ss-EPI DWI (130.46±49.10 vs. 71.58±30.43, P=0.000; 33.22±18.86 vs. 17.92±18.72, P=0.003). The scores of overall image quality, ghost artifact where next to the paranasal sinuses, mastoid air cells and frontal sinus of Rs-EPI DWI were significantly higher than those of Ss-EPI DWI. Meanwhile, the geometric distortion of anatomical structures of Rs-EPI DWI were significantly lower compared to Ss-EPI DWI sequence (0.016±0.021 vs. 0.037±0.069, P=0.00). The inter-reader and intra-reader agreements for the assessment of qualitative parameters were good [0.74≤Kappa value or ICC≤0.92]. CONCLUSIONS: Rs-EPI DWI sequence is a potential technique to improve the imaging quality in the diagnosis of intracranial mass lesions.

Pulse Pressure Variation Adjusted by Respiratory Changes in Pleural Pressure, Rather Than by Tidal Volume, Reliably Predicts Fluid Responsiveness in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: 1) To evaluate the ability of pulse pressure variation adjusted by respiratory changes in pleural pressure to predict fluid responsiveness compared with pulse pressure variation alone. 2) To identify factors explaining the poor performance of pulse pressure variation in acute respiratory distress syndrome. DESIGN: Prospective study. SETTING: Forty-bed university hospital general ICU. PATIENTS: Ninety-six mechanically ventilated acute respiratory distress syndrome patients requiring fluid challenge. INTERVENTIONS: Fluid challenge, 500 mL saline over 20 minutes. MEASUREMENTS AND MAIN RESULTS: Before fluid challenge, esophageal pressure was measured at the end-inspiratory and end-expiratory occlusions. Change in pleural pressure was calculated as the difference between esophageal pressure measured at end-inspiratory and end-expiratory occlusions. Hemodynamic measurements were obtained before and after the fluid challenge. Patients were ventilated with tidal volume 7.0 ± 0.8 mL/kg predicted body weight. The fluids increased cardiac output by greater than 15% in 52 patients (responders). Adjusting pulse pressure variation for changes in pleural pressure (area under the receiver operating characteristic curve, 0.94 [0.88-0.98]) and the ratio of chest wall elastance to total respiratory system elastance (area under the receiver operating characteristic curve, 0.93 [0.88-0.98]) predicted fluid responsiveness better than pulse pressure variation (area under the receiver operating characteristic curve, 0.78 [0.69-0.86]; all p < 0.01). The gray zone approach identified a range of pulse pressure variation/changes in pleural pressure values (1.94-2.1) in 3.1% of patients for whom fluid responsiveness could not be predicted reliably. On logistic regression analysis, two independent factors affected the correct classification of fluid responsiveness at a 12% pulse pressure variation cutoff: tidal volume (adjusted odds ratio 1.57/50 mL; 95% CI, 1.05-2.34; p = 0.027) and chest wall elastance/respiratory system elastance (adjusted odds ratio, 2.035/0.1 unit; 95% CI, 1.36-3.06; p = 0.001). In patients with chest wall elastance/respiratory system elastance above the median (0.28), pulse pressure variation area under the receiver operating characteristic curve was 0.94 (95% CI, 0.84-0.99) compared with 0.76 (95% CI, 0.61-0.87) otherwise (p = 0.02). CONCLUSIONS: In acute respiratory distress syndrome patients, pulse pressure variation adjusted by changes in pleural pressure is a reliable fluid responsiveness predictor despite the low tidal volume (< 8 mL/kg). The poor predictive ability of pulse pressure variation in acute respiratory distress syndrome patients is more related to low chest wall elastance/respiratory system elastance ratios than to a low tidal volume.

Dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in a mouse model of experimental silicosis.

CONTEXT: Silicosis is a devastating, irreversible lung fibrosis condition exposed to crystalline silica. The mononuclear phagocyte system plays an important role in the pathogenesis of silicosis. OBJECTIVE: The present study was aimed to explore the dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in experimental silicosis model. MATERIALS AND METHODS: A mouse model of lung fibrosis was developed with crystalline silica particles (2 mg/40 µL via oropharyngeal instillation) using male C57BL/6 mice, and were killed on days 1, 3, 7, 14, and 28. The lung inflammation and fibrosis was investigated using hematoxylin-eosin staining and bronchoalveolar lavage fluid (BALF) analysis, Masson's trichrome staining, and immunofluorescence. Circulating monocyte subsets (Ly6C(hi) and Ly6C(lo)), polarization state of BALF-derived alveolar macrophages (AMϕ) and lung interstitial macrophages (IMϕ, derived from enzymatically digested lung tissue) were analyzed by flow cytometry. RESULTS: The percentage of Ly6C(hi) monocytes significantly increased on day 1 after silica exposure, which reached the peak level from day 7 till day 28. Moreover, M2 (alternative activation) AMϕ (PI - CD64 + CD206+) was dramatically and progressively increased from day 1 to day 28. A parallel increase in IMϕ with M2 polarization (PI-CD64 + CD11b + CD206+) was also observed from day 1 to day 28. CONCLUSION: Our data demonstrate a dynamic view of mononuclear phagocyte change in three compartments after silica challenge, which highlights the remodeling of mononuclear phagocyte system as a potential therapeutic target for silicosis.

[Radiation Dose of Body Surface at Sensitive Organs and Its Protective Precaution in Head CT Scanning:Initial Experience.]

OBJECTIVES: To investigate the radiation dose of body surface at sensitive organs using different protective precaution in head CT scanning. METHODS: The standard phantom received head routine sequence scanning with dual-source computed tomography.The phantoms were scanned with three different protective precaution:group A (without protective clothing),group B (wearing lead collar and cover lead clothes),group C (wearing lead collar and clothes without cuffs).The thermoluminescence dosimeters (TLD) was placed on the body surface corresponding to sensitive organs to measure radiation dose. RESULTS: The volume of CT dose index (CTDIvol) and dose length product (DLP) in group A,B and C were same,44.06 mGy and 634 mGy×cm,respectively.There was no statistic significant difference between group A,B and C of radiation dose in non-protective region (P=0.712).The radiation dose in the neck region under the cover of lead collar in group A,B and C were (2.57 ± 0.65) mGy,(2.30 ± 1.10) mGy and (2.48 ± 0.90) mGy,respectively,without statistic significant difference between groups (P=0.816).However,the radiation dose in abdominal region of group A was (0.66±0.37) mGy,which was significantly higher than that of group B [(0.18 ± 0.18) mGy] and group C [(0.18±0.16) mGy],The radiation dose in dorsal region of group A was (0.55±0.43) mGy,which was significantly higher than that of group B [(0.28±0.22) mGy],while that of group C [(0.14±0.12) mGy] was significantly lower than group B. CONCLUSIONS: Compared to traditional lead coverage,lead collar and cloth can decrease the radiation dose of body surface and sensitive organs in head scan with dual source CT.

Neutrophil extracellular traps in ischemia-reperfusion injury-induced myocardial no-reflow: therapeutic potential of DNase-based reperfusion strategy.

Emerging evidence suggests a potential role of neutrophil extracellular traps (NETs) in linking sterile inflammation and thrombosis. We hypothesized that NETs would be induced during myocardial ischemia-reperfusion (I/R), and NET-mediated microthrombosis may contribute to myocardial "no-reflow". Male Wistar rats were randomly divided into I/R control, DNase (DNase I, 20 µg/rat), recombinant tissue-type plasminogen activator (rt-PA, 420 µg/rat), DNase + rt-PA, and sham control groups after 45-min myocardial ischemia. In situ NET formation, the anatomic "no re-flow" area, and infarct size were evaluated immediately after 3 h of reperfusion. Long-term left ventricular (LV) functional and histological analyses were performed 45 days after operation. Compared with the I/R controls, the DNase + rt-PA group exhibited reduced NET density [8.38 ± 1.98 vs. 26.86 ± 3.07 (per 200 × field), P < 0.001] and "no-flow" area (15.22 ± 0.06 vs. 34.6 ± 0.05%, P < 0.05) in the ischemic region, as well as reduced infarct size (38.39 ± 0.05 vs. 71.00 ± 0.03%, P < 0.001). Additionally, compared with the I/R controls, DNase + rt-PA treatment significantly ameliorated I/R injury-induced LV remodeling (LV ejection fraction: 64.22 ± 3.37 vs. 33.81 ± 2.98%, P < 0.05; LV maximal slope of the LV systolic pressure increment: 3,785 ± 216 vs. 2,596 ± 299 mmHg/s, P < 0.05). The beneficial effect was not observed in rats treated with DNase I or rt-PA alone. Our study provides evidence for the existence of NETs in I/R-challenged myocardium and confirms the long-term benefit of a novel DNase-based reperfusion strategy (DNase I + rt-PA), which might be a promising option for the treatment of myocardial I/R injury and coronary no-reflow.