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Zhou L.,Chinese Academy of Sciences | Zhou L.,University of Chinese Academy of Sciences | Chen Z.,Chinese Academy of Sciences | Wang F.,Chinese Academy of Sciences | And 3 more authors.
Acta Biomaterialia | Year: 2013

A non-viral siRNA carrier composed of mono-methoxy-poly (3-hydroxybutyrate-co-4-hydroxybutyrate)-block-polyethylene glycol-block-linear polyethyleneimine (mP3/4HB-b-PEG-b-lPEI) was synthesized using 1800 Da linear polyethyleneimine and evaluated for siRNA delivery. Our study demonstrated that siRNA could be efficiently combined with mP3/4HB-b-PEG-b-lPEI (mAG) co-polymer and was protected from nuclease degradation. The combined siRNA were released from the complexes easily under heparin competition. The particle size of the mAG/siRNA complexes was 158 nm, with a ζ-potential of around 28 mV. Atomic force microscopy images displayed spherical and homogeneously distributed complexes. The mAG block co-polymer displayed low cytotoxicity and efficient cellular uptake of Cy3-siRNA in A549 cells by flow cytometry and confocal microscopy. In vitro transfection efficiency of the block co-polymer was assessed using siRNA against luciferase in cultured A549-Luc, HeLa-Luc, HLF-Luc, A375-Luc and MCF-7-Luc cells. A higher transfection efficiency and lower cytotoxicity was obtained by mAG block co-polymer in five cell lines. Furthermore, a remarkable improvement in luciferase gene silencing efficiency of the mAG complex (up to 90-95%) over that of Lipofectamine™ 2000 (70-82%) was observed in HLF-Luc and A375-Luc cells. Additionally, a mAG/p65-siRNA complex also showed a better capability than Lipofectamine™ 2000/p65-siRNA complex to drastically reduce the p65 mRNA level down to 10-16% in HeLa, U251 and HUVEC cells at an N/P ratio of 70. Crown Copyright © 2013 Published by Elsevier Ltd. on behalf of Acta Materialia Inc. All rights reserved.

Chen G.,Guangzhou Medical College | Zhang W.,Sun Yat Sen University | He J.,Guangzhou Institute of Respiratory Diseases
Journal of Computer Assisted Tomography | Year: 2012

Objective: This study aimed to improve the diagnosis of inflammatory myofibroblastic tumor (IMT) in the mediastinum by analysis of computed tomographic (CT) images. Materials and Methods: Clinical data, CT, and pathological findings of 6 patients diagnosed with IMT in the mediastinum were retrospectively analyzed. Results: Of the 6 patients, 5 were women, and mean age at diagnosis was 34 years. All the lesions were solid soft tissue masses and ranged in maximum diameter from 5.0 to 8.5 cm, which were located in the anterior (n = 1), middle (n = 2), and posterior mediastinum (n = 3). The anterior mediastinal tumor had a clear boundary. The tumors in the middle mediastinum had indistinct boundaries: one was invading the right wall of the trachea and the other was invading the esophageal wall. A tumor located in the right posterior mediastinum caused osteolysis of the adjacent ribs. A small amount of calcification was seen in the tumor in the right posterior-inferior mediastinum. After administration of contrast, all tumors showed varying degrees of contrast enhancement (range, 17-47 HU) on chest CT scan. Recurrence occurred in only 1 case. Conclusions: The common CT appearance of IMT in the mediastinum is as a soft tissue mass with uniform density. All tumors show varying degrees of contrast enhancement. Some lesions have clear boundaries; others do not. Computed tomography examination can help to determine the areas involved by lesions and their relationships with adjacent tissues, which facilitates the prediction of the likely surgical requirements. Copyright © 2012 by Lippincott Williams & Wilkins.

Fan J.,Chinese PLA General Hospital | Li X.,Chinese PLA General Hospital | Cheng Y.,Chinese PLA General Hospital | Yao C.,Peking University | Zhong N.,Guangzhou Institute of Respiratory Diseases
Clinical and Investigative Medicine | Year: 2011

Purpose: Advanced age and hospitalization are associated with increasing risk of venous thromboembolic (VTE) events. The aim of this study was to investigate whether elevated D-dimer levels could predict VTE events in elderly patients hospitalized for acute illness. Methods: 458 consecutive patients (65% men; mean age, 77 ± 7 years) who were older than 60 years, immobilized for ≥ 3 days, and hospitalized for heart failure, respiratory fail- ure, acute ischemic stroke, or acute infectious disease without pharmacological prophylaxis or recent major surgery, were enrolled. Elevated D-dimer levels were defined as > 500 ng/ml. VTE events included symptomatic VTE within 90 days or asymptomatic deep venous thrombosis screened by compression ultrasonography at enrollment and 3-week follow-up. The association between baseline D-dimer levels and subsequent VTE events, adjusted for age, sex, ethnicity, body mass index, co-morbidities, and acute disease status, was assessed using multivariate Cox proportional hazard models. Results: 49.1% (n = 225) of patients had elevated baseline D-dimer levels, and of these patients, 14.2% (n = 32) developed VTE during the 90-day follow-up. In contrast, only 5.6% (n = 13) of patients with normal D-dimer levels developed VTE. Multivariate analy- sis showed that patients with elevated D-dimer levels had a 3.2-fold increased risk of devel- oping VTE (95% confidence interval, 1.5-6.5; P = 0.002) in comparison with patients with normal levels. Conclusions: In elderly patients who were hospitalized for acute medical illness, elevated D-dimer levels are associated with subsequent VTE events. Our data suggest that meas- urement of D-dimer, a widely-performed objective test, may help clinicians address high-risk individuals for VTE. © 2011 CIM.

Zhou L.,Chinese Academy of Sciences | Zhou L.,University of Chinese Academy of Sciences | Chen Z.,Chinese Academy of Sciences | Chi W.,Chinese Academy of Sciences | And 4 more authors.
Biomaterials | Year: 2012

A class of non-viral siRNA vectors consisting of biodegradable poly(hydroxyalkanoates) (PHA) grafted onto branched poly(ethyleneimine) (bPEI, 25kDa) was synthesized and evaluated for siRNA delivery. The mPHA- g-bPEI copolymers were synthesized through Michael addition between acrylated mono-methoxy-poly(hydroxyalkanoates) (mPHA-acrylated) and bPEI with various block length poly(hydroxyalkanoates) from 1300 to 2900Da. Our research showed that mPHA- g-bPEI copolymers could effectively bind siRNA, protect it from degradation by nucleases and efficiently release the complexed siRNA in the presence of low concentrations of polyanionic heparin. The particle size of mPHA- g-bPEI/siRNA complexes was <200nm with ζ-potential between 33 and 43mV. mPHA- g-bPEI copolymers displayed low cytotoxicity compared to unmodified bPEI and efficient cellular uptake of Cy3-siRNA in A549 cells by flow cytometry and confocal microscopy. siRNA delivery efficiency of the copolymers was assessed by siRNA against luciferase in cultured A549-Luc and MCF-7-Luc cells. Those mPHA- g-bPEI copolymers revealed a higher transfection efficiency and lower cytotoxicity than bPEI in two cell lines. Furthermore, a remarkable knockdown of luciferase expression of mPHA- g-bPEI (mAP2) complex (up to 85%) invitro was found to be equivalent to that of commercially available transfection agent Lipofectamine™ 2000. © 2011 Elsevier Ltd.

Shi C.-Z.,Jinan University | Zhao Q.,Guangzhou University | Luo L.-P.,Jinan University | He J.-X.,Guangzhou University | And 2 more authors.
Journal of Thoracic Disease | Year: 2014

Objective: The purpose of this study was to analyze the role of the sizes of solitary pulmonary nodules (SPNs) in predicting their potential malignancies. Methods: A total of 379 patients with pathologically confirmed SPNs were enrolled in this study. They were divided into three groups based on the SPN sizes: ≤10, 11-20, and >20 mm. The computed tomography (CT) findings of these SPNs were analyzed in these three groups to identify the malignant and benign SPNs. The risk factors were analyzed using binary logistic regression analysis. Results: Of these 379 patients, 120 had benign SPNs and 259 had malignant SPNs. In the ≤10 mm SPN group, air cavity density was the risk factor for malignancy, with the sensitivity, specificity, and accuracy being 77.8%, 75.0%, and 76.3%. In the 11-20 mm SPN group, age, glitches and vascular aggregation were the risk factors for malignancy, with the sensitivity, specificity, and accuracy being 91.3%, 56.9%, and 81.5%. In the >20 mm SPN group, age, lobulation, and vascular aggregation were the risk factors for malignancy, with the sensitivity, specificity, and accuracy being 88.6%, 57.1%, and 79.1%. Conclusions: According to CT findings of SPNs, age, glitches, lobulation, vascular aggregation, and air cavity density are the risk factors of malignancy, whereas calcification and satellite lesions are the protective factors. During the course of development from small to large nodules, air cavity density could be firstly detected in early stages, followed by glitches and vascular aggregation. Lobulation is associated with relatively large lesions. © Pioneer Bioscience Publishing Company.

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