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Bian C.,Nanjing Medical University | Bian C.,Nanjing Jiangbei Peoples Hospital | Li Z.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | Xu Y.,Nanjing Medical University | And 3 more authors.
World Journal of Surgical Oncology | Year: 2015

Background: Whole-exome sequencing has shown that lung adenocarcinoma (LAC) can be driven by mutant genes, including TP53, P16, and Smad4. The aim of this study was to clarify protein alterations of P53, P16, and Smad4 and to explore their correlations between the protein alterations and clinical outcome. Methods: We investigated associations among P53 mutant (P53Mut) expression, and P16 and Smad4 loss-of-expression, with clinical outcome in 120 LAC patients who underwent curative resection, using immunohistochemical (IHC) methods. Results: Of the 120 patients, 76 (63.3%) expressed P53Mut protein, whereas 54 (45.0%) loss of P16 expressed and 75 (62.5%) loss of Smad4 expressed. P53Mut expression was associated with tumor size (P = 0.041) and pathological stage (P = 0.025). Loss of P16 expression was associated with lymph node metastasis (P = 0.001) and pathological stage (P < 0.001). Loss of Smad4 expression was associated with tumor size (P = 0.033), lymph node metastasis (P = 0.014), pathological stage (P = 0.017), and tumor differentiation (P = 0.022). Kaplan-Meier survival analysis showed that tumor size (P = 0.031), lymph node metastasis (P < 0.001), pathological stage (P < 0.001), P53Mut protein expression (P = 0.038), and loss of p16 or Smad4 expression (P < 0.001) were significantly associated with shorter overall survival(OS), whereas multivariate analysis indicated that lymph node metastasis (P = 0.014) and loss of p16 or Smad4 expression (P < 0.001) were independent prognostic factors. Analysis of protein combinations showed patients with more alterations had poorer survival (P < 0.001). Spearman correlation analysis showed that loss of Smad4 expression inversely correlated with expression of P53Mut (r = -0.196, P = 0.032) and positively with lost P16 expression (r =0.182, P = 0.047). Conclusions: The findings indicate that IHC status of P53Mut, P16, and Smad4 may predict patient outcomes in LAC. © Bian et al.; licensee BioMed Central.

PubMed | Zhuzhou City Hospital, Nanjing University of Traditional Chinese Medicine, Nanjing Jiangbei Peoples Hospital and Nanjing Chest Hospital
Type: Journal Article | Journal: Molecular medicine reports | Year: 2015

The aim of the current study was to explore the effects and possible mechanisms of tripterygium glycosides tablet (TGT) in the treatment of active ankylosing spondylitis (AS). Thirty-six patients with active AS were given a 20 mg TGT treatment three times per day for 12 weeks, and 21 unrelated healthy controls were recruited as the control group. Efficacy measures included the Bath AS disease activity index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) prior and subsequent to TGT treatment. Serum dickkopf homolog 1 (DKK1) and interleukin-17 (IL-17) levels before and after TGT treatment were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA assay. The levels of several serum biomarkers were determined by ELISA, including receptor activator of nuclear factor -B ligand (RANKL), osteoprotegerin (OPG), bone alkaline phosphatase (BAP), bone morphogenetic protein-2 (BMP-2), matrix metalloproteinase-3 (MMP-3), cross-linked telopeptide of type II collagen (CTX-II), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2). After 12 weeks of TGT treatment, the BASDAI score of the patients was significantly reduced (P<0.05), their levels of ESR and CRP were significantly reduced to a normal level (P<0.05, P<0.05), RT-PCR and ELISA showed a significant increase in the level of DKK1 expression (P<0.05) and a significant decreased IL-17 expression (P<0.05), there was a significant increase in the expression of OPG, BAP and BMP-2 (P<0.01, P<0.01, P<0.01) and a significant reduction in the expression levels of RANKL, CTX-II. MMP-3, PGE2, and VEGF (P<0.01, P<0.01, P<0.01, P<0.05, P<0.01) compared with those of the controls. TGT is effective at improving the signs and symptoms of patients with AS through the regulation of serum biomarkers, and the mechanisms may be associated with the anti-inflammatory effect, inhibition of new bone formation and potential bone-protective effects.

Hong M.,Nanjing Thoracic Hospital | Jiang Z.,Nanjing Southeast University | Zhou Y.-F.,Nanjing Jiangbei Peoples Hospital
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: To investigate the effects of double radiofrequency hyperthermia on Th1/Th2 cells in esophageal cancer patients treated with radiotherapy. Materials and Methods: 22 patients with esophageal cancer were divided into a radiotherapy group (10 cases) and a combined group (double radiofrequency hyperthermia combined with radiotherapy group, 12 cases). Both groups received conventional radiotherapy using a cobalt-60 therapy apparatus (TD60-66Gy/30-33F). Patients in the combined group also underwent double radiofrequency hyperthermia (2F/W, 8-10F). Before and after treatment, Th1, Th2, Tc1 and Tc2 cells in peripheral blood were determined with flow cytometry. Results: In the radiotherapy group, Th1 cell contents before and after radiotherapy were 17.5±5.26% and 9.69±4.86%, respectively, with a significant difference (p<0.01). The Th1/Th2 ratio was significantly decreased from 28.2±14.3 to 16.5±10.4 (p<0.01). In the combined group, Th1 cell content before radiotherapy was 15.9±8.18%, and it increased to 18.6±8.84 after radiotherapy (p>0.05), the Th1/Th2 ratio decreasing from 38.4±36.3 to 28.1±24.0 (p>0.05). Changes in Th2, Tc1 and Tc2 cell levels were not significant in the two groups before and after therapy (p>0.05). Conclusions: Double radiofrequency hyperthermia can promote the conversion from Th2 to Th1 cells, and regulate the balance of Th1/Th2 cells.

Zhou J.,Nanjing Jiangbei Peoples Hospital | Zhang H.-J.,Jiangsu Province Peoples Hospital
World Chinese Journal of Digestology | Year: 2015

AIM: To investigate the expression of potassium channel tetramerization domain-containing 12 (KCTD-12) protein in gastrointestinal stromal tumors (GISTs) of the stomach and its clinical significance. METHODS: The expression of KCTD-12 was immunohistochemically examined in 39 gastric GIST tissues, and its correlations with the clinicopathological parameters, National Institutes of Health (NIH) risk classification and Ki-67 labeling index were analyzed. Univariate and Cox multivariate analyses were used to evaluate the factors associated with 3-year recurrence-free survival (RFS) rate of patients with gastric GISTs. RESULTS: Positive KCTD-12 expression was detected in 29 (74.4%) of the 39 gastric GIST tissues. The absence of KCTD-12 expression was associated with large tumor size, high mitotic count and NIH high-risk classification (P < 0.05). GISTs recurred after surgery in 10 of the 39 cases during the follow-up, and the 3-year RFS rate was 74.4%. Univariate analysis showed that tumor size, NIH risk classification, KCTD-12 expression and Ki-67 labeling index had an impact on the 3-year RFS rate of patients with GISTs of the stomach. On multivariate analysis, KCTD-12 [relative risk (RR) = 0.014; 95%CI: 0.001-0.320, P = 0.007] was shown to be a highly correlated predictor. The 3-year RFS rate of patients without KCTD-12 expression was only 30% compared with 89.7% in those with KCTD-12 expression (P = 0.001). The 3-year RFS rate of patients with KCTD-12 expression and a Ki-67 labeling index of 5% or less was 95.7%. The 3-year RFS rate of patients without KCTD-12 expression and a Ki-67 labeling index more than 5% was only 20%. CONCLUSION: KCTD-12 is a useful and reliable biomarker for the prognosis of GISTs of the stomach, especially when combined with Ki-67 labeling index. © 2015 Baishideng Publishing Group Inc. All rights reserved.

Tang X.-L.,Nanjing University of Technology | Lin B.-L.,Nanjing University of Technology | Cui S.,Nanjing University of Technology | Zhang X.,Nanjing University of Technology | And 5 more authors.
RSC Advances | Year: 2016

In this paper, the preparation of Fe3O4/PTX/HSA nanoparticles with magnetic resonance imaging (MRI) and slow release functionality by a self-assembly method is presented. Firstly, hydrophobic Fe3O4 nanoparticles with an average size of 10 nm are synthesized by thermal decomposition of an iron-oleate complex and then modified and stabilized by hydrophobic paclitaxel (PTX). Lastly, Fe3O4/PTX nanoparticles with a 3 nm PTX shell on the Fe3O4 surface are loaded into human serum albumin (HSA) to form uniform Fe3O4/PTX/HSA nanoparticles by PTX-HSA interaction after breaking the disulfide bond and unfolding hydrophobic region of HSA. The novel PTX modified Fe3O4/PTX nanoparticles have good dispersity in ethanol and strong binding capacity with HSA, which can be homogenously dispersed in HSA matrices to form novel Fe3O4/PTX/HSA nanoparticles with a pie structure by the self-assembly method. The resulting Fe3O4/PTX/HSA nanoparticles with a high saturation magnetization value of 10.2 emu g-1, good T2 imaging functionality and excellent ability to cross the cell membrane have been demonstrated by magnetization curves, in vitro MRI and cellular uptake. Furthermore, the in vitro antitumor ability of the system has also been evaluated. © The Royal Society of Chemistry 2016.

Feng H.,Nanjing Medical University | Feng H.,Nanjing Jiangbei Peoples Hospital | Zhoua X.,Nanjing Medical University | Zhang G.,Nanjing Medical University
European Journal of Gastroenterology and Hepatology | Year: 2014

Cirrhosis is a severe threat to public health. Some studies have suggested that cirrhosis is associated with Helicobacter pylori infection, but the results remain controversial. This meta-analysis was conducted to quantify the association between cirrhosis and H. Pylori infection. Published articles on H. Pylori prevalence in patients with cirrhosis were collected to assess the potential associations between H. Pylori infection and cirrhosis risk. Twenty-one eligible studies were included for the analysis. Data on publication year, geographic region, and etiology were summarized. Metaregression models and subgroup analyses were established to screen the factors for heterogeneity. Of the 322 articles retrieved, 21 met the inclusion criteria. These studies involved 6135 cases, with a total H. Pylori infection rate of 52.26%. This meta-analysis showed significant difference in H. Pylori infection between patients with cirrhosis and controls [odd ratio (OR)=2.05, 95% confidence interval (CI): 1.33-3.18, P<0.0001]. The subgroup analysis revealed, in contrast to Asia (OR=0.90, 95% CI: 0.48-1.66, P<0.0001), Europe (OR=2.98, 95% CI: 2.02-4.39, P<0.0001), and America (OR=4.75, 95% CI: 1.42-15.95, P=0.249), a significantly higher prevalence of H. Pylori infection in patients with cirrhosis. On the basis of etiology, there was a higher prevalence of H. Pylori infection due to primary biliary cirrhosis (OR=1.75, 95% CI: 1.15-2.64, P=0.147) and viral cirrhosis (OR=2.66, 95% CI: 1.24-5.71, P<0.0001) compared with alcohol cirrhosis (OR=0.77, 95% CI: 0.04-16.59, P<0.0001). The pooled data suggest that there is a significantly high prevalence of H. Pylori infection in patients with cirrhosis. Large-scale and multicenter studies are needed to further investigate the relation between cirrhosis and H. Pylori infection. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Feng H.,Nanjing Jiangbei Peoples Hospital | Yin J.,Nanjing Jiangbei Peoples Hospital | Han Y.-P.,Nanjing Medical University | Zhou X.-Y.,Nanjing Medical University | Zhang G.-X.,Nanjing Medical University
International Journal of Clinical and Experimental Medicine | Year: 2015

CD64 was up-regulated in infection diseases, but there was no report about the change of CD64 in chronic hepatitis B virus (HBV) infection. The purpose of this study was to determine whether there was a dynamic change of CD 64 index and to judge the value to antiviral treatment. 96 CHB patients were enrolled and selected 33 healthy adults as control. We detected the level of CD64, found the level of CD64 were significantly increased in chronic HBV infection patients, especially the lymphocyte CD64 (8.12 ± 0.23 vs. 6.25 ± 0.27; P < 0.001). Further, we proved CD64 index was increased in various stages of chronic HBV infection. ROC curve analysis showed the level of lymphocyte CD64 had higher AUC value than neutrophil or monocyte. Then we monitor longitudinally the impact of the treatment with interferon-α and found that the suppression of viral replication induced by interferon-α resulted in a decrease in CD64 index. In conclusion, this study showed that CD64 index was increased in chronic HBV infection patients and changed with the course of disease, the therapy of interferon-α would correct it, and analysis prompted that the level of lymphocyte CD64 would be more suitable for as a biomarker to judge the condition of chronic HBV infection and the curative effect of interferon-α treatment. © 2015, E-Century Publishing Corporation. All rights reserved.

Su C.,University of Sichuan | Su C.,Nanjing Jiangbei Peoples Hospital | Ju S.,University of Sichuan | Liu Y.,University of Sichuan | Yu Z.,University of Sichuan
Intelligent Data Analysis | Year: 2015

Decision tree is a simple and effective method and it can be supplemented with ensemble methods to improve its performance. Random Forest and Rotation Forest are two approaches which are perceived as "classic" at present. They can build more accurate and diverse classifiers than Bagging and Boosting by introducing the diversities namely randomly chosen a subset of features or rotated feature space. However, the splitting criteria used for constructing each tree in Random Forest and Rotation Forest are Gini index and information gain ratio respectively, which are skew-sensitive. When learning from highly imbalanced datasets, class imbalance impedes their ability to learn the minority class concept. Hellinger distance decision tree (HDDT) was proposed by Chawla, which is skew-insensitive. Especially, bagged unpruned HDDT has proven to be an effective way to deal with highly imbalanced problem. Nevertheless, the bootstrap sampling used in Bagging can lead to ensembles of low diversity compared to Random Forest and Rotation Forest. In order to combine the skew-insensitivity of HDDT and the diversities of Random Forest and Rotation Forest, we use Hellinger distance as the splitting criterion for building each tree in Random Forest and Rotation Forest respectively. An experimental framework is performed across a wide range of highly imbalanced datasets to investigate the effectiveness of Hellinger distance, information gain ratio and Gini index which are used as the splitting criteria in ensembles of decision trees including Bagging, Boosting, Random Forest and Rotation Forest. In addition, Balanced Random Forest is also included in the experiment since it is designed to tackle class imbalance problem. The experimental results, which contrasted through nonparametric statistical tests, demonstrate that using Hellinger distance as the splitting criterion to build individual decision tree in forest can improve the performances of Random Forest and Rotation Forest for highly imbalanced classification. © 2015 - IOS Press and the authors. All rights reserved.

Su C.,University of Sichuan | Su C.,Nanjing Jiangbei Peoples Hospital | Ju S.,University of Sichuan | Liu Y.,University of Sichuan | Yu Z.,University of Sichuan
Intelligent Data Analysis | Year: 2015

Rule-learning extracts the knowledge from a dataset and represent it in a form that is easy for people to understand. RIPPER (Repeated Incremental Pruning to Produce Error Reduction) and PART (Partial Decision Trees) are two well-known schemes for rule-learning. However, due to overpruning of RIPPER and skew-sensitivity of PART, it is difficult to use two methods to learn from imbalanced datasets. To bypass these difficulties, we propose a K-L divergence-based PART (KLPART) that use K-L divergence as a splitting criterion to build partial decision trees. An experimental framework is carried out with a wide range of imbalanced datasets over RIPPER, PART, KLPART and the combination of these methods for classification with SMOTE processing. The results obtained, which contrasted through nonparametric statistical tests, show that KLPART is robust in the presence of class imbalance, especially when combined with SMOTE. We thereby recommend the use of KLPART with SMOTE when learning from imbalanced datasets. © 2015 IOS Press and the authors.

Su C.,University of Sichuan | Su C.,Nanjing Jiangbei Peoples Hospital | Ju S.,University of Sichuan | Liu Y.,University of Sichuan | Yu Z.,University of Sichuan
Intelligent Automation and Soft Computing | Year: 2014

Learning from imbalanced datasets is a challenging topic and plays an important role in data mining community. Traditional splitting criteria such as information gain are sensitive to class distribution. In order to overcome the weakness, Hellinger Distance Decision Trees (HDDT) is proposed by Cieslak and Chawla. Despite HDDT outperforms the traditional decision trees, however, there may be other skew-insensitive splitting criteria. In this paper, we propose some new skew-insensitive splitting criteria which can be used in the construction of decision trees and applied a comprehensive empirical evaluation framework testing against commonly used sampling and ensemble methods, considering performance across 58 datasets. Based on the experimental results, we demonstrate the superiority of these skew-insensitive decision trees on the datasets with high imbalanced level and competitive performance on the datasets with low imbalanced level and K-L divergence-based decision tree (KLDDT) is the most robust among these skew-insensitive decision trees in the presence of class imbalance, especially when combined with SMOTE. Thus, we recommend the use of KLDDT with SMOTE when learning from high imbalanced datasets. Finally, we used these skew-insensitive decision trees to build the diagnosis model of chronic obstructive pulmonary disease in traditional Chinese Medicine. The results show that KLDDT is the most effective method. © 2014, © 2014 TSI® Press.

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