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Meng-Jie Gu,1,* Kun-Feng Li,1,* Lan-Xin Zhang,1 Huan Wang,1 Li-Si Liu,2 Zhuo-Zhao Zheng,2 Nan-Yin Han,1 Zhen-Jun Yang,1 Tian-Yuan Fan1 1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 2Department of Radiology, Peking University Third Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. Keywords: magnetic resonance imaging, gadolinium, liposomes, tenascin-C, GBI-10 aptamer, tumor targeting

Xing-Hui Shao,1 Yan-Min Yang,1 Jun Zhu,1 Han Zhang,1 Yao Liu,1 Xin Gao,1 Li-Tian Yu,1 Li-Sheng Liu,1 Li Zhao,2 Peng-Fei Yu,3 Hua Zhang,4 Qing He,5 Xiao-Dan Gu6 1Emergency and Intensive Care Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Department of Emergency, Fu Xing Hospital, Capital Medical University, Beijing, 3Department of Cardiology, Pingdu People’s Hospital, Pingdu, 4Department of Emergency, Qingdao Municipal Hospital, Qingdao, 5Department of Emergency, West China Hospital, Sichuan University, Chengdu, 6Department of Emergency, Sixth People’s Hospital of Chengdu, Chengdu, People’s Republic of China Background: Atrial fibrillation (AF) disproportionately affects older adults. However, direct comparison of clinical features, medical therapy, and outcomes in AF patients aged 65–74 and ≥75 years is rare. The objective of the present study was to evaluate the differences in clinical characteristics and prognosis in these two age-groups of geriatric patients with AF.Materials and methods: A total of 1,336 individuals aged ≥65 years from a Chinese AF registry were assessed in the present study: 570 were in the 65- to 74-year group, and 766 were in the ≥75-year group. Multivariable Cox hazards regression was performed to analyze the major adverse cardiac events (MACEs) between groups.Results: In our population, the older group were more likely to have coronary artery disease, hypertension, previous stroke, cognitive disorder, or chronic obstructive pulmonary disease, and the 65- to 74-year group were more likely to have valvular heart disease, left ventricular systolic dysfunction, or sleep apnea. The older patients had 1.2-fold higher mean CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke) scores, but less ­probability of being prescribed drugs. Compared with those aged 65–74 years, the older group had a higher risk of death (hazard ratio 2.881, 95% confidence interval 1.981–4.189; P

A reliable and efficient regeneration protocol from the cotyledons and hypocotyls is successfully established using three cauliflower genotypes. Thidiazuron (TDZ) is found to be an effective inducer of shoot formation. Both the hypocotyl and cotyledon segments are highly responsive (100%) to shoot formation and produce a maximum of 15.8 shoots per hypocotyl explant on MS salts with B5 vitamins medium containing TDZ at 0.2 mg L-1 and α-naphthaleneacetic acid at 0.01 mg L-1. Using this efficient regeneration protocol, the reporter β-glucuronidase (GUS) under the constitutive cauliflower mosaic virus (CaMV) 35S promoter is introduced into cauliflower cells of hypocotyls and cotyledons with Agrobacterium tumefaciens strain EHA105. By optimizing the parameters on the procedure of Agrobacterium-mediated transformation, a high transformation efficiency is demonstrated. The transformation efficiencies are 21.6% and 18.3% for cotyledons and hypocotyls, respectively. Integration of the transgenes in the plant genome is demonstrated by PCR and Southern hybridization analysis. Expression of the transgenes is confirmed by RT-PCR analysis and GUS staining. Compared with previous works, the present study provides higher regeneration and transformation efficiencies and establishes a highly efficient transformation system in cauliflower. [ABSTRACT FROM AUTHOR]

Exposure to particulate matter (PM) air pollution has been shown to exacerbate children's asthma, but the exposure sources and temporal characteristics are still under study. Children's exposure to PM is likely to involve both combustion-related ambient PM and PM related to a child's activity in various indoor and outdoor microenvironments. Among 19 children with asthma, 9-17 years of age, we examined the relationship of temporal changes in percent predicted forced expiratory volume in 1 sec (FEV[1]) to personal continuous PM exposure and to 24-hr average gravimetric PM mass measured at home and central sites. Subjects were followed for 2 weeks during either the fall of 1999 or the spring of 2000, in a southern California region affected by transported air pollution. FEV[1] was measured by subjects in the morning, afternoon, and evening. Exposure measurements included continuous PM using a passive nephelometer carried by subjects; indoor, outdoor home, and central-site 24-hr gravimetric PM[2.5] (PM of aerodynamic diameter < 2.5 microm) and PM[10]; and central-site hourly PM[10], nitrogen dioxide, and ozone. Data were analyzed with linear mixed models controlling for within-subject autocorrelation, FEV[1] maneuver time, and exposure period. We found inverse associations of FEV[1] with increasing PM exposure during the 24 hr before the FEV[1] maneuver and with increasing multiday PM averages. Deficits in percent predicted FEV[1] (95% confidence interval) for given PM interquartile ranges measured during the preceding 24-hr were as follows: 128 microg/m[3] 1-hr maximum personal PM, -6.0% (-10.5 to -1.4); 30 microg/m[3] 24-hr average personal PM, -5.9% (-10.8 to -1.0); 6.7 microg/m[3] indoor home PM[2.5], -1.6% (-2.8 to -0.4); 16 microg/m[3] indoor home PM[10], -2.1% (-3.7 to -0.4); 7.1 microg/m[3] outdoor home PM[2.5], -1.1% (-2.4 to 0.1); and 7.5 microg/m[3] central-site PM[2.5], -0.7% (-1.9 to 0.4). Stronger associations were found for multiday moving averages of PM for both personal and stationary-site PM. Stronger associations with personal PM were found in boys allergic to indoor allergens. FEV[1] was weakly associated with NO[2] but not with O[3]. Results suggest mixed respiratory effects of PM in asthmatic children from both ambient background exposures and personal exposures in various microenvironments. [ABSTRACT FROM AUTHOR]

In this article we present results from a 2-year comprehensive exposure assessment study that examined the particulate matter (PM) exposures and health effects in 108 individuals with and without chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), and asthma. The average personal exposures to PM with aerodynamic diameters < 2.5 microm (PM[2.5]) were similar to the average outdoor PM[2.5] concentrations but significantly higher than the average indoor concentrations. Personal PM[2.5] exposures in our study groups were lower than those reported in other panel studies of susceptible populations. Indoor and outdoor PM[2.5], PM[10] (PM with aerodynamic diameters < 10 microm), and the ratio of PM[2.5] to PM10 were significantly higher during the heating season. The increase in outdoor PM[10] in winter was primarily due to an increase in the PM[2.5] fraction. A similar seasonal variation was found for personal PM[2.5]. The high-risk subjects in our study engaged in an equal amount of dust-generating activities compared with the healthy elderly subjects. The children in the study experienced the highest indoor PM[2.5] and PM[10] concentrations. Personal PM[2.5] exposures varied by study group, with elderly healthy and CHD subjects having the lowest exposures and asthmatic children having the highest exposures. Within study groups, the PM[2.5] exposure varied depending on residence because of different particle infiltration efficiencies. Although we found a wide range of longitudinal correlations between central-site and personal PM[2.5] measurements, the longitudinal r is closely related to the particle infiltration efficiency. PM[2.5] exposures among the COPD and CHD subjects can be predicted with relatively good power with a microenvironmental model composed of three microenvironments. The prediction power is the lowest for the asthmatic children. [ABSTRACT FROM AUTHOR]

Background: Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes, and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension. We assessed the effects of the routine administration of an angiotensin converting enzyme (ACE) inhibitor-diuretic combination on serious vascular events in patients with diabetes, irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs.Methods: The trial was done by 215 collaborating centres in 20 countries. After a 6-week active run-in period, 11 140 patients with type 2 diabetes were randomised to treatment with a fixed combination of perindopril and indapamide or matching placebo, in addition to current therapy. The primary endpoints were composites of major macrovascular and microvascular events, defined as death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction, and new or worsening renal or diabetic eye disease, and analysis was by intention-to-treat. The macrovascular and microvascular composites were analysed jointly and separately. This trial is registered with ClinicalTrials.gov, number NCT00145925.Findings: After a mean of 4.3 years of follow-up, 73% of those assigned active treatment and 74% of those assigned control remained on randomised treatment. Compared with patients assigned placebo, those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg. The relative risk of a major macrovascular or microvascular event was reduced by 9% (861 [15.5%] active vs 938 [16.8%] placebo; hazard ratio 0.91, 95% CI 0.83-1.00, p=0.04). The separate reductions in macrovascular and microvascular events were similar but were not independently significant (macrovascular 0.92; 0.81-1.04, p=0.16; microvascular 0.91; 0.80-1.04, p=0.16). The relative risk of death from cardiovascular disease was reduced by 18% (211 [3.8%] active vs 257 [4.6%] placebo; 0.82, 0.68-0.98, p=0.03) and death from any cause was reduced by 14% (408 [7.3%] active vs 471 [8.5%] placebo; 0.86, 0.75-0.98, p=0.03). There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline.Interpretation: Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events, including death. Although the confidence limits were wide, the results suggest that over 5 years, one death due to any cause would be averted among every 79 patients assigned active therapy. [ABSTRACT FROM AUTHOR]