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Prognostic value of coronary atherosclerosis progression evaluated by coronary CT angiography in patients with stable angina
Gu, H; Gao, Y; Hou, ZH; Schoepf, UJ; Snyder, AN; Duguay, TM; Wang, XM; Lu, B
EUROPEAN RADIOLOGY 2018年 28卷3期 页码:1066-1076
MULTIDETECTOR COMPUTED-TOMOGRAPHY; ARTERY CALCIUM; INTRAVASCULAR ULTRASOUND; PLAQUE CHARACTERIZATION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; AMERICAN-COLLEGE; NATURAL-HISTORY; RISK; ASSOCIATION
To investigate the progression of coronary atherosclerosis burden by coronary CT angiography (CCTA) and to demonstrate its association with the incidence of major adverse cardiac events (MACE). We retrospectively studied patients with stable angina who had undergone repeat CCTA due to recurrent or worsening symptoms. Lipid-rich, fibrous, calcified and total plaque burden as well as coronary diameter stenosis were quantitatively analysed. The incidence of MACE during follow-up was determined. The final cohort consisted of 268 patients (mean age 52.9 +/- 9.8 years, 71 % male) with a mean follow-up period of 4.6 +/- 0.9 years. Patients with lipid-rich, fibrous, calcified and total plaque burden (%) progression, as well as coronary diameter stenosis (%) progression had a significantly higher incidence of MACE than those without (all p < 0.05). The progression of lipid-rich plaque (HR = 1.601, p = 0.021), total plaque burden (HR = 2.979, p = 0.043) and coronary diameter stenosis (HR = 4.327, p < 0.001) were independent predictors of MACE (all p < 0.05). Patients presenting with recurrent or worsening symptoms associated with coronary artery disease who have coronary atherosclerosis progression on CCTA are at an increased risk of future MACE. aEuro cent Repeat CCTA can provide information regarding the progression of coronary atherosclerosis. aEuro cent Coronary atherosclerosis progression at CCTA is independently associated with MACE. aEuro cent CCTA findings could serve as incremental predictors of MACE.
Cilostazol protects diabetic rats from vascular inflammation via nuclear factor-kappa B-dependent down-regulation of vascular cell adhesion molecule-1 expression.
Gao Ling;Wang Furong;Wang Bo;Gong Bendi;Zhang Jie;Zhang Xiumei;Zhao Jiaju
J Pharmacol Exp Ther 2006年 318卷1期 页码:53-8
Animals|Diabetes Mellitus, Experimental/drug therapy/metabolism|Down-Regulation/drug effects/physiology|Endothelium, Vascular/drug effects/metabolism|Gene Expression Regulation/drug effects/physiology|Male|NF-kappa B/antagonists & inhibitors/metabolism|Rats|Rats, Sprague-Dawley|Tetrazoles/pharmacology/therapeutic use|Vascular Cell Adhesion Molecule-1/biosynthesis|Vascular Diseases/metabolism/prevention & contro
Vascular cell adhesion molecule (VCAM)-1 plays a critical role in the initiation and development of vascular inflammation and selective inhibition of adhesion molecules expressed by endothelial cells may present a new therapeutic strategy for the treatment of vascular complications associated with diabetes mellitus. Increasing evidence indicates that cilostazol, a cAMP phosphodiesterase inhibitor, reduces VCAM-1 expression on endothelial cells. In this study, we have tested the effect of cilostazol on the development of vascular inflammation in rats with streptozotocin-induced diabetes and determined the mechanism by which cilostazol prevents diabetes-induced vascular inflammation in the aorta. Diabetic rats were treated with different dose of cilostazol (27 or 9 mg/kg/day) for 8 weeks, and aortae were removed for the evaluation of vascular inflammation. The VCAM-1 protein expression and VCAM-1 mRNA transcripts were analyzed by immunohistochemical staining and in situ hybridization assay, respectively. Our results demonstrated that cilostazol treatment prevents the overexpression of VCAM-1 and protects diabetic rats from vascular inflammation. More importantly, our mechanistic studies suggested that cilostazol controls the VCAM-1 overexpression via inhibiting the activation of nuclear factor-kappaB.
Association of the CTLA4 gene with Graves' disease in the Chinese Han population.
Zhao Shuang-Xia;Pan Chun-Ming;Cao Huang-Ming;Han Bing;Shi Jing-Yi;Liang Jun;Gao Guan-Qi;Peng Yong-De;Su Qing;Chen Jia-Lun;Zhao Jia-Jun;Song Huai-Don
PLoS One 2010年 5卷3期 页码:e9821
Antigens, CD/genetics|CTLA-4 Antigen|Case-Control Studies|China|Cohort Studies|False Positive Reactions|Gene Frequency|Genetic Predisposition to Disease|Genotype|Geography|Graves Disease/ethnology/genetics|Humans|Models, Genetic|Odds Ratio|Polymorphism, Single Nucleotide|Regression Analysi
To determine whether genetic heterogeneity exists in patients with Graves' disease (GD), the cytotoxic T-lymphocyte associated 4 (CTLA-4) gene, which is implicated a susceptibility gene for GD by considerable genetic and immunological evidence, was used for association analysis in a Chinese Han cohort recruited from various geographic regions. Our association study for the SNPs in the CTLA4 gene in 2640 GD patients and 2204 control subjects confirmed that CTLA4 is the susceptibility gene for GD in the Chinese Han population. Moreover, the logistic regression analysis in the combined Chinese Han cohort revealed that SNP rs231779 (allele frequencies p = 2.81x10(-9), OR = 1.35, and genotype distributions p = 2.75x10(-9), OR = 1.42) is likely the susceptibility variant for GD. Interestingly, the logistic regression analysis revealed that SNP rs35219727 may be the susceptibility variant to GD in the Shandong population; however, SNP, rs231779 in the CTLA4 gene probably independently confers GD susceptibility in the Xuzhou and southern China populations. These data suggest that the susceptibility variants of the CTLA4 gene varied between the different geographic populations with GD.
Chronic palmitate exposure inhibits AMPKalpha and decreases glucose-stimulated insulin secretion from beta-cells: modulation by fenofibrate.
Sun Ying;Ren Meng;Gao Guan-qi;Gong Bendi;Xin Wei;Guo Hua;Zhang Xiu-juan;Gao Ling;Zhao Jia-ju
Acta Pharmacol Sin 2008年 29卷4期 页码:443-50
AMP-Activated Protein Kinases/antagonists & inhibitors|Animals|Cell Culture Techniques|Cell Line, Tumor|Cells, Cultured|Dose-Response Relationship, Drug|Fenofibrate/pharmacology|Glucose/pharmacology|Insulin/secretion|Insulin-Secreting Cells/drug effects/metabolism|Insulinoma/metabolism|Islets of Langerhans/cytology/drug effects/physiology|Luminescence|Luminescent Measurements|Male|PPAR alpha/metabolism|Palmitates/pharmacology|Rats|Rats, Wista
Adenosine monophosphate-activated protein kinase (AMPK), a vital regulator of glucose metabolism, may affect insulin secretion in beta-cells. However, the role of AMPK in beta-cell lipotoxicity remains unclear. Fenofibrate has been reported to regulate lipid homeostasis and is involved in insulin secretion in pancreatic beta-cells. In the present study, we aimed to investigate the effect of palmitate on AMPK expression and glucose-stimulated insulin secretion (GSIS) in rat islets and INS-1 beta-cell, as well as the effect of fenofibrate on AMPK and GSIS in INS-1 cells treated with palmitate.
The screening and analysis of protein signatures and signaling associated with chemoresistance based on Protein Pathway Array technology in gastric cancer
Lian, GD;Li, LP;Ye, F;Wang, DG;Liu, JL;Shi, YL;Jing, CQ;Suo, J;Zhang, DY;Chen, M
ONCOLOGY REPORTS 2018年 39卷1期 页码:307-315
RANDOMIZED CONTROLLED-TRIAL; ADJUVANT CHEMOTHERAPY; THERAPEUTIC TARGETS; LUNG-CANCER; 5-FLUOROURACIL; RESISTANCE; SURGERY; CELLS; MODEL; PREDICTION
The present study was aimed to identify proteins associated with signaling pathways involved in chemoresistance, and establish a predictive model for chemoresistance in gastric cancer patients after radical surgery. A total of 140 clinically-staged III gastric cancer samples from patients after D2 radical gastrectomy were enrolled in the present study. Protein Pathway Array (PPA) and 286 antibodies were used to assess the protein expression in tumor tissues of patients. The Significance Analysis of Microarray (SAM) software and clustering and discriminant analysis were used to identify differentially expressed proteins between chemosensitive and chemoresistant subsets, and a predictive model for chemoresistance was established using the independent predictive factors. The Ingenuity Pathway Analysis (IPA) software was also used to investigate the relationship between proteins and the signaling transduction network. A total of 23 proteins were differentially expressed between 67 chemosensitive and 73 chemoresitant tumor tissues. Six proteins including PLK1 and DACH1 were independent risk factors for chemoresistance. A predictive model for chemoresistance by these proteins was established, and the accuracy, the sensitivity, and the specificity of this modal was 89.3, 90.3 and 88.2%, respectively. In addition, the present study revealed that differentially expressed proteins were closely related to cellular activity, DNA methylation and DNA damage and repair, and also involved in the ERK/MAPK, Wnt/beta-catenin, PI3K/AKT, apoptosis and p53 signaling pathways. In conclusion, the predictive model established by PPA may be an effective detection system for predicting the chemosensitivity of gastric cancer patients after D2 gastrectomy.
Identification of a novel mutation in the FGFR3 gene in a Chinese family with Hypochondroplasia
Chen, J;Yang, JF;Zhao, SZ;Ying, H;Li, GM;Xu, C
GENE 2018年 641卷 页码:355-360 影响因子:2.319
GROWTH-FACTOR RECEPTOR-3; MISSENSE MUTATIONS; ACHONDROPLASIA; DOMAIN; DYSPLASIAS; PHENOTYPE; DWARFISM
Background: Hypochondroplasia (HCH; OMIM 146000) is a common autosomal dominant skeletal dysplasia characterized by disproportionate short stature, short extremities, relative macrocephaly, and lumbar lordosis. Because of its clinical and genetic heterogeneity, gene mutational analysis is particularly important in diagnosis and the phenotypes may be ameliorated if diagnosed early.;-;Materials and methods: In this study, we examined a Chinese family with HCH, performed an inductive analysis of their clinical features and radiographic results, and applied targeted exome sequencing (TES) technology to perform a molecular diagnosis.;-;Results: The proband and his mother all presented disproportionate short stature, short, stubby extremities, unchanged interpedicular distances from L1 - L5, and short iliac bones, with a 'fish mouth -shaped' sciatic notch. The mother received induced abortion recently because an ultrasound showed short femur length of her fetus at 24-week gestation. Eventually, a novel heterozygous mutation (c.1145G > A) in FGFR3 was identified by TES in the proband, his mother, and her fetus; this causes the substitution of glycine with aspartic acid in codon 382.;-;Conclusions: In this study, we diagnosed a Chinese pedigree with HCH based on clinical data, radiographic features, and genetic testing results. Our results extend the genetic mutation spectrum of FGFR3 and demonstrate that TES is an effective method for the diagnosis of skeletal dysplasia in clinical practices.
Invasive placenta previa: Placental bulge with distorted uterine outline and uterine serosal hypervascularity at 1.5T MRI - useful features for differentiating placenta percreta from placenta accreta
Chen, X;Shan, RQ;Zhao, LX;Song, QX;Zuo, CT;Zhang, XJ;Wang, SS;Shi, HL;Gao, F;Qian, TY;Wang, GB;Limperopoulos, C
EUROPEAN RADIOLOGY 2018年 28卷2期 页码:708-717
ABNORMAL PLACENTATION; ULTRASOUND; DIAGNOSIS; PREGNANCY; SPECTRUM; US
To characterise MRI features of invasive placenta previa and to identify specific features for differentiating placenta percreta (PP) from placenta accreta (PA).;-;Forty-five women with PP and 93 women with PA who underwent 1.5T placental MRI were included. Two radiologists independently evaluated the MRI features of invasive placenta previa, including our novel type of placental bulge (i.e. placental bulge type-II, characterized by placental bulge with distorted uterine outline). Pearson's chi-squared or Fisher's two-sided exact test was performed to compare the MRI features between PP and PA. Logistic stepwise regression analysis and the area under the receiver operating characteristic curve (AUC) were performed to select the optimal features for differentiating PP from PA.;-;Significant differences were found in nine MRI features between women with PP and those with PA (P < 0.05). Placental bulge type-II and uterine serosal hypervascularity were independently associated with PP (odds ratio = 48.618, P < 0.001; odds ratio = 4.165, P = 0.018 respectively), and the combination of the two MRI features to distinguish PP from PA yielded an AUC of 0.92 for its predictive performance.;-;Placental bulge type-II and uterine serosal hypervascularity are useful MRI features for differentiating PP from PA.
Livin serves as a prognostic marker for mid-distal rectal cancer and a target of mid-distal rectal cancer treatment
Su, QB;Wang, LY;Wei, GN;Liao, LZ;Zhao, J;Liu, HJ;Shi, YL;Li, LP;Li, CS
ONCOLOGY LETTERS 2017年 14卷6期 页码:7759-7766
COLORECTAL-CANCER; PELVIC RECURRENCE; BREAST-CANCER; APOPTOSIS; EXPRESSION; RESECTION; SURVIVIN; IAPS; ADENOCARCINOMA; THERAPEUTICS
Livin is a novel member of the inhibitor of apoptosis protein family, which has been identified to be expressed in various malignancies and is suggested to be associated with poor prognostic significance. However, no data are available concerning the significance of livin in mid-distal rectal cancer. In the present study, livin expression, and its association with clinicopathological characteristics and prognosis was examined in patients with mid-distal rectal cancer. Apoptotic susceptibility, invasion capacity and chemosensitivity of LoVo cells were investigated using small interfering RNA (siRNA)-mediated knockdown of livin. It was revealed that livin was highly expressed in mid-distal rectal cancer tissues compared with the normal rectal mucosal tissues. Livin expression was associated with pathological grade, extent of invasion (T stage) and extent of lymph node metastasis (N stage) of tumor, contributing to poor prognosis of mid-distal rectal cancer following surgery. The data suggest that aggressive surgery should be applied in patients with mid-distal rectal cancer with high expression of livin. It was also revealed that knockdown of livin by siRNA increased the apoptotic rate, suppressed invasion of LoVo cells, and decreased the half-maximal inhibitory concentration of oxaliplatin and 5-fluorouracil by similar to 50% in LoVo cells significantly compared with control groups. The data suggested that a combination of downregulation of livin and anticancer drugs may significantly decrease the toxicity of anticancer drugs. Taken together, the present study indicated that livin may be a promising target in clinical therapy of mid-distal rectal cancer.
MicroRNA-138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9
Hu, B;Wang, JB;Jin, XB
ONCOLOGY LETTERS 2017年 14卷6期 页码:7583-7588
HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; DOWN-REGULATION; LUNG-CANCER; CYCLIN D3; MIR-138; METASTASIS; PRINCIPLES; MECHANISM; THERAPY
An accumulating number of studies have reported that the expression levels of microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types, including renal cell carcinoma (RCC). miRNAs play essential functions in tumorigenesis and the progression of tumors by serving as oncogenes or tumor suppressors. Recently, the expression and functions of miR-138 have been studied in a number of human cancer types; however, its role in RCC remains poorly understood. In the present study, the results revealed that miR-138 was significantly downregulated in RCC cell lines and tissues, and that low expression levels of miR-138 were correlated with histological grade, tumor stage and lymph node metastasis. In functional studies, restoration of miR-138 expression inhibited cell proliferation and invasion of ACHN and A498 cells. In addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9 knockdown inhibited cell proliferation and invasion of RCC, with a similar effect to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the disease. These findings indicate that miR-138 may present a novel target for therapeutic strategies in RCC.
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