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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.
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.
The anti-hepatocellular carcinoma activity of Mel-P15 is mediated by natural killer cells
Xu, T;Cui, TX;Peng, LP;Kong, S;Zou, JQ;Tian, XS
ONCOLOGY LETTERS 2017年 14卷6期 页码:6901-6906
ANTIMICROBIAL ACTIVITY; INTERFERON-GAMMA; IN-VIVO; MELITTIN; PEPTIDE; CANCER; RECOGNITION; APOPTOSIS; BACTERIA; INNATE
Mel-P15 is a peptide derived from melittin, the main toxic component in the venom of the European honeybee Apis mellifera. In the present study, the antitumor effects of Mel-P15 and the underlying molecular mechanisms of these effects in vivo were investigated. Mel-P15 directly stimulated natural killer (NK) cell cytotoxicity in vitro, which was increased to 55.45% at a 4 mu g/ml dose of Mel-P15. In the mouse liver cancer (H22) xenograft mice model, Mel-P15 suppressed tumor growth in vivo; the tumor inhibitory rate was 61.15% following treatment with 2 mg/kg Mel-P15. In addition, the immune response was activated following Mel-P15 treatment. Mel-P15 treatment increased the spleen and thymus indices, promoted splenocyte proliferation, stimulated NK cytotoxicity and upregulated the secretion of cytokines, including interleukin-2, interferon-gamma and tumor necrosis factor-a. In addition, the tumor inhibitory effect of Mel-P15 on BEL-7402-bearing nude mice was abrogated by the selective depletion of NK cells via the intraperitoneal injection of an anti-asialo GM-1 antibody. The results suggest that Mel-P15 inhibits tumor growth in vivo by promoting NK cell cytotoxicity. Mel-P15 may therefore be a potential immunotherapy candidate for the treatment of hepatocellular carcinoma.
Association between serum gamma-glutamyltransferase and chronic kidney disease in urban Han Chinese: a prospective cohort study
Shen, ZW;Xing, J;Wang, QL;Faheem, A;Ji, X;Li, J;Bian, WW;Jiang, Z;Li, XJ;Xue, FZ;Liu, J
INTERNATIONAL UROLOGY AND NEPHROLOGY 2017年 49卷2期 页码:303-312
UNILATERAL URETERAL OBSTRUCTION; DOSE-RESPONSE METAANALYSIS; CROSS-SECTIONAL SURVEY; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; METABOLIC SYNDROME; KOREAN MEN; US ADULTS; RISK
Limited numbers of literatures have focused on the association between gamma-glutamyltransferase (GGT) and chronic kidney disease (CKD), and their results were controversial. Therefore, in this study, we set up a large-scale cohort of Chinese population to discover and verify the association between serum GGT and CKD.;-;Our cohort study was based on 21,818 patients who visited Health Management Center of Shandong Provincial Hospital, China, to receive routine health check-up during the period of 2005-2010, and we used multivariate Cox regression model to clarify whether elevated serum GGT increased the risk of CKD or not.;-;During the follow-up of 57,891 person-years, 1456 patients developed CKD, giving rise to an incidence density of 25.15 per 1000 person-years (1456/57,891 person-years). After adjusting gender, age, baseline serum creatinine (SCr), body mass index (BMI), serum albumin (ALB), alanine aminotransferase (ALT), hemoglobin, white blood cell count (WBC), triglyceride (TG), total cholesterol (TC), hypertension, cardiovascular disease (CVD), diabetes, smoking and drinking status, the risk for CKD increased with the elevated serum GGT quartiles. The hazard ratio (HR) for CKD was 1.326 (95 % confidence interval (CI), 1.073-1.639) when the top quartile of serum GGT was compared with the bottom one, and the HR of log-transformed serum GGT for CKD was 1.658 (95 % CI, 1.294-2.125). The results were consistent in males but different in females when gender was stratified.;-;The result reveals that there is a positive relationship between increasing serum GGT levels and the incidence of CKD which suggests that elevated GGT level could be a potential indicator for risk of CKD.
Olfactory dysfunction in the APP/PS1 transgenic mouse model of Alzheimer's disease: Morphological evaluations from the nose to the brain
Yao, ZG;Hua, F;Zhang, HZ;Li, YY;Qin, YJ
NEUROPATHOLOGY 2017年 37卷6期 页码:485-494 影响因子:1.556
ENTORHINAL CORTEX ACTIVITY; AMYLOID-BETA; NASAL CAVITY; BULB; EPITHELIUM; MICE; CELLS; INTERNEURONS; DEPOSITION; DEMENTIA
Olfactory dysfunction is among the signs of Alzheimer's disease (AD) and cognitive impairment. It has been demonstrated A was associated with olfactory impairment observed in both transgenic mice and in AD patients. In this study, we evaluated amyloid deposition in the olfactory circuit of APP/PS1 transgenic mouse model of AD, which showed olfactory dysfunction in olfactory behavior tests. We found amyloid depositions were widely distributed in the whole olfactory circuit. Moreover, we think these amyloid depositions contribute to neuronal atrophy, dendritic abnormalities, synapse loss and axonal degeneration. Therefore, there was a correlation between olfactory deficits and amyloid deposition. Our findings provide initial insights into the pathological basis of AD-related olfactory dysfunction.
Enhancing effects of basic fibroblast growth factor and fibronectin on osteoblast adhesion to bone scaffolds for bone tissue engineering through extracellular matrix-integrin pathway
Feng, L;Li, YH;Zeng, WC;Xia, B;Zhou, DS;Zhou, J
EXPERIMENTAL AND THERAPEUTIC MEDICINE 2017年 14卷6期 页码:6087-6092
MESENCHYMAL STEM-CELLS; RAT OSTEOBLASTS; OSTEOGENIC DIFFERENTIATION; IN-VITRO; PROLIFERATION; SURFACES; ATTACHMENT; EXPRESSION; PEPTIDE; PROTEIN
The present study aimed to investigate the effects of basic fibroblast growth factor (bFGF) and fibronectin (FN) on adhesion of osteoblasts seeded into bio-derived bone scaffolds. Rat calvarial osteoblasts were separated and their osteogenic phenotypes were determined by staining for alkaline phosphatase as well as alizarin red staining. The bio-derived bone scaffolds were prepared from the metaphysis of porcine femur and their physicochemical properties were assessed by scanning electron microscopy (SEM) and X-ray diffraction analysis. An MTT assay was used to detect the effects of bFGF and FN on osteoblast adhesion or proliferation on cell/scaffold constructs through blocking the extracellular matrix FN-integrin pathway by the Gly-Arg-Gly-Asp-Ser (GRGDS) peptide. Western blot analysis was used to measure the beta 1 integrin levels. Based on the adhesion of osteoblasts stimulated by various concentrations of bFGF (0.1, 1, 10 and 100 ng/ml) on bio-derived bone scaffolds modified by various concentrations of FN (0.1, 1, 10 and 100 mu g/ml), the cell/scaffold constructs were divided into four groups: i) Control, non-stimulated and nonmodified group; ii) 10 mu g/ml FN-modified group; iii) 100 ng/ml bFGF-stimulated group; iv) 10 mu g/ml FN + 100 ng/ml bFGF group. Cell proliferation curves acquired by MTT assay and micrographs obtained by SEM showed that the combination of bFGF and FN significantly improved cell adhesion, particularly in the 10 mu g/ml FN + 100 ng/ml bFGF group vs. the other groups, and the effect on cell adhesion was inhibited by 1 mmol/l GRGDS peptide through the FN-integrin pathway. Western blot results showed that the combination of bFGF and FN significantly enhanced beta 1 integrin expression levels. These results suggested that osteoblasts stimulated by 100 ng/ml bFGF and bio-derived bone materials modified by 10 mu g/ml FN should be combined to be applied in the bone tissue engineering.
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