RAF Inhibitors Activate the MAPK Pathway by Relieving Inhibitory Autophosphorylation

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中国北方汉族人寻常型天疱疮与HLA-A、B单倍型的相关性研究

目的:探讨HLA-A、B单倍型与中国东北地区汉族人寻常型天疱疮的相关性。方法:采用标准微量淋巴细胞毒试验方法对寻常型天疱疮患者组及正常对照组进行HLA-I类抗原分型并计算单倍型频率进行比较。结果:与对照组比较,寻常型天疱疮患者组中单倍型HLA-A2、B5,HLA-A2、B13,HLA-A3、B40,HLA-A3、B13,HLA-A3、B16,HLA-A3、B5和HLA-A10、B40的频率明显增高(P<0.05),而单倍型HLA-A2、B46在患者组中未发现。结论:特异单倍型可能是决定寻常型天疱疮发生的重要因素。     

Determination of the optimal energy level in spectral CT imaging for displaying abdominal vessels in pediatric patients

Purpose

To determine the optimal energy level in contrast-enhanced spectral CT imaging for displaying abdominal vessels in pediatric patients.

Materials and methods

This retrospective study was institutional review board approved. 15 children (8 males and 7 females, age range, 6–15 years, mean age 10.1 ± 3.1 years) underwent contrast-enhanced spectral CT imaging for diagnosing solid tumors in abdomen and pelvic areas were included. A single contrast-enhanced scan was performed using a dual energy spectral CT mode with a new split contrast injection scheme (iodixanol at 1–1.5 ml/kg dose. 2/3 first, 1/3 at 7–15 s after the first injection). 101 sets of monochromatic images with photon energies of 40–140 keV with 1 keV interval were reconstructed. Contrast-noise-ratio (CNR) for hepatic portal or vein were generated and compared at every energy level to determine the optimal energy level to maximize CNR. 2 board-certified radiologists interpreted the selected image sets independently for image quality scores.

Results

CT values and CNR for the vessels increased as photon energy decreased from 140 to 40 keV: (CT value: 48.29–570.12 HU, CNR: 0.08–14.90) in the abdominal aorta, (58.48–369.73 HU, 0.64–5.87) in the inferior vena cava, and (58.48–369.73 HU, 0.06–6.96) in the portal vein. Monochromatic images at 40–50 keV (average 42.0 ± 4.67 keV) could display vessels above three levels clearly, and with excellent image quality scores of 3.17 ± 0.58 (of 4) (k = 0.50). The CNR values at the optimal energy level were significantly higher than those at 70 keV, an average energy corresponding to the conventional 120 kVp for abdominal CT imaging.

Conclusion

Spectral CT imaging provides a set of monochromatic images to optimize image quality and enhance vascular visibility, especially in the hepatic portal and vein systems. The best CNR for displaying abdominal vessels in children was obtained at 42 keV photon energy level.     

Flow characteristics of the proximal pulmonary arteries and vena cava in patients with chronic thromboembolic pulmonary hypertension: correlation between 3.0 T phase-contrast MRI and right heart catheterization

PURPOSE

We aimed to determine the correlation between flow characteristics of the proximal pulmonary arteries and vena cava obtained by 3.0 T phase-contrast magnetic resonance imaging (MRI) and hemodynamic characteristics by right heart catheterization in patients with chronic thromboembolic pulmonary hypertension.

MATERIALS AND METHODS

Twenty consecutive patients with chronic thromboembolic pulmonary hypertension and 20 sex- and age-matched healthy volunteers were included prospectively. All patients and controls underwent phase-contrast MRI to determine the flow characteristics including peak velocity, mean velocity, and mean blood flow of the proximal pulmonary artery and vena cava. All patients underwent right heart catheterization to determine the hemodynamics.

RESULTS

Peak velocity and mean velocity of the proximal pulmonary artery were significantly lower in the patient group. In patients, both peak velocity and mean blood flow were sequentially decreased in the main pulmonary artery, left and right pulmonary arteries, and left and right interlobar pulmonary arteries. Inferior vena cava had higher peak velocity, mean velocity, and mean blood flow than superior vena cava. Peak velocity of the main pulmonary artery correlated with mean and diastolic pulmonary artery pressure. Peak velocity of both inferior and superior vena cava strongly correlated with the pulmonary vascular resistance index (PVRI) (r=−0.68, P < 0.001 and r=−0.74, P < 0.001, respectively). Mean velocity of the main pulmonary artery and right pulmonary artery strongly correlated with PVRI and mean pulmonary artery pressure. Mean velocity of the superior vena cava and mean blood flow of the main pulmonary artery strongly correlated with PVRI and right cardiac work index.

CONCLUSION

Blood flow in the proximal pulmonary artery and vena cava evaluated by phase-contrast MRI correlate with hemodynamic parameters of right heart catheterization and can be used to noninvasively evaluate the severity of chronic thromboembolic pulmonary hypertension and, potentially, to follow up the treatment response.Chronic thromboembolic pulmonary hypertension (CTEPH) develops as a result of obstruction of pulmonary arterial vessels by organized thromboembolic material and subsequent vascular remodeling in small unobstructed vessels, and it is associated with significant morbidity and mortality (1). Right heart catheterization remains the reference standard to diagnose CTEPH, assess the hemodynamic disturbance, and follow up the treatment response; but it is invasive, delivers radiation, and is associated with recognized complications (2, 3).Magnetic resonance imaging (MRI) is considered not only as the reference standard for evaluation of ventricular function, but it also provides a reproducible and noninvasive assessment of hemodynamics changes in pulmonary hypertension (4). In a separate validation study, cardiac MRI-derived parameters showed a strong correlation with invasive determinations (5).In a study by Mohiaddin et al. (6), phase-contrast MRI was used to confirm reduced diastolic peak velocity of the inferior vena cava (IVC) in patients with pulmonary hypertension. Only one study reported blood flow conditions in the proximal pulmonary arteries and vena cava in healthy children (7). To our knowledge, no study has assessed proximal pulmonary artery and vena cava flow or evaluated correlation of the flow determined by phase-contrast MRI and hemodynamics by right heart catheterization in CTEPH.We performed a prospective study to observe the flow change in the proximal pulmonary artery, superior vena cava (SVC) and inferior vena cava (IVC) in patients with CTEPH by phase-contrast MRI, and to evaluate the correlation of the proximal pulmonary artery and vena cava flow with hemodynamics derived by right heart catheterization in patients with CTEPH.     

Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study

Breast Cancer Research and Treatment - Tumor features associated with aggressive cancers may affect cognition prior to systemic therapy. We evaluated associations of cognition prior to adjuvant...     

Fatal Balamuthia mandrillaris infection with red plaques on the nasal dorsum as the first presentation

Balamuthia mandrillaris infection is a rare infectious disease around the world, with high rates of morbidity and mortality. Its early and correct diagnosis is a big challenge for us, and without it the delay in starting effective treatment can lead to the development of encephalitis. This is a report of a case of Balamuthia mandrillaris infection in a Chinese boy, with red plaques on the nasal dorsum as the first presentation, who finally developed into fatal encephalitis. The authors have reviewed the related literature and share the special skin features in order to favor the early diagnosis of the disease and increase the chances of survival.     

Suppression of FPR2 expression inhibits inflammation in preeclampsia by improving the biological functions of trophoblast via NF-κB pathway

Journal of Assisted Reproduction and Genetics - The dysfunction of trophoblast during inflammation plays an important role in PE. Formyl peptide receptor 2 (FPR2) plays crucial roles in the...     

Genetic variants in the angiopoietin-2 gene are associated with increased risk of ARDS

Objective  Angiopoietin-2 (Ang-2) is a potent regulator of vascular permeability and inflammation in acute lung injury and acute respiratory distress syndrome (ARDS). Genetic variants in the Ang-2 gene may lead to altered activities of Ang-2 (or ANGPT2) gene. The aim of this study was to assess if genetic variants of Ang-2 are associated with the risk of ARDS. Design  Unmatched, case-control study nested within a prospectively enrolled cohort. Setting  Intensive care units (ICU) of an academic medical center. Patients  About 1,529 critically ill patients with risk factors for ARDS consecutively admitted to the ICUs from 1999 to 2006. Cases were 449 patients who developed ARDS and controls were 1,080 subjects who did not developed ARDS. Intervention  None. Measurements and results  Nine tagging SNPs (tSNPs) spanning the entire Ang-2 gene were genotyped in all patients. The results were analyzed using logistic regression models, adjusting for covariates. The variant T allele of one tSNP (rs2515475) was significantly associated with increased risk of ARDS (OR_adjusted = 1.28; P = 0.042). This association was stronger in subjects with extrapulmonary injuries (OR_adjusted = 1.79; P = 0.004). Haplotype TT in block 2 containing the T allele of the rs2515475 was also significantly associated with higher risk of ARDS (OR_adjusted = 1.42; P = 0.009), particularly in subjects with extrapulmonary injuries (OR_adjusted = 1.90; P = 0.004). Conclusion  Common genetic variation in the Ang-2 gene may be associated with increased risk of ARDS, especially among patients with extrapulmonary injuries. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. L. Su and R. Zhai contributed equally to this work.