Integrated network analysis to identify the key genes, transcription factors, and microRNAs involved in hepatocellular carcinoma.

HCC (hepatocellular carcinoma), which can be induced by cirrhosis and viral hepatitis infection, is the most frequent form of liver cancer. This study is performed to investigate the mechanisms of HCC. GSE57957 was obtained from Gene Expression Omnibus database, including 39 HCC samples and 39 adjacent non-tumorous samples. The DEGs (differentially expressed genes) were screened using the limma package in R, and then were conducted with enrichment analysis using "BioCloud" platform. Using STRING database, WebGestalt tool, as well as ITFP and TRANSFAC databases, PPI (protein-protein interaction) pairs, miRNA (microRNA)-target pairs, and TF (transcription factor)-target pairs separately were predicted. Followed by integrated network was constructed by Cytoscape software and module analysis was performed using the MCODE plugin of Cytoscape software. There were 518 DEGs identified from the HCC samples, among which 17 up-regulated genes (including MCM2, MCM6, and CDC20) and 5 down-regulated genes could also function as TFs. In the integrated network for the down-regulated genes, FOS and ESR1 had higher degrees, and both of them were targeted by miR-221 and miR-222. Additionally, MCM2 had interaction with MCM6 in the up-regulated module with the highest score. MCM2, MCM6, CDC20, FOS, ESR1, miR-221 and miR-222 might affect the pathogenesis of HCC.

Prognostic value of pathologic grade for patients with oral squamous cell carcinoma.

OBJECTIVE: The purposes of this study were to explore both the prognostic value of pathologic grade and the relationships between differentiation and clinicopathological characteristics in oral squamous cell carcinoma. METHODS: This retrospective cohort study included the records of 2036 patients with oral squamous cell carcinoma who were surgically treated from June 1999 to December 2011. Chi-square test, Kaplan-Meier analysis, and Cox proportional hazards regression model were performed for statistical analysis. RESULTS: Many clinicopathological characteristics were associated with pathologic grade. Kaplan-Meier analysis showed that well-differentiated tumors had a better prognosis than the other two grades. Cox regression model showed that differentiation was an independent risk factor for prognosis in patients with early stage, but not with advanced stage. The predictive abilities of pathologic grade, T stage, N status, and lymph node ratio were similar, but the presence of extracapsular spread and perineural invasion were stronger prognostic factors than pathologic differentiation. CONCLUSIONS: Pathologic grade was found to be an independent risk factor for early-stage oral squamous cell carcinoma, but not for advanced stage. Many important clinicopathological characteristics were associated with histological classification; however, its prognostic value was limited.

[Treatment of intractable aspiration after partial laryngectomy by cuffed tracheostomy tube with inner cannula].

Objective: To evaluate the efficacy of cuffed tracheostomy tube with inner cannula for the treatment of intractable aspiration after partial laryngectomy. Methods: From May 2010 to June 2015, 15 patients with intractable aspiration after partial laryngectomy of laryngeal and hypopharyngeal carcinoma were enrolled. Cuffed tracheostomy tube with inner cannula was used in the 15 patients for treatment of intractable aspiration. The patients and their family were trained to manage the cuffed tracheostomy tube with inner cannula and to eat since the 14th day after surgery. Cuff was initially inflated with 10 ml air and then deflated of 0.5 ml air every 2-3 days. Until the inflation of cuff was no longer required, the cuffed tracheostomy tube was replaced by metal tracheostomy tube. The patients' swallowing function and aspiration were evaluated 6 months after treatment. Results: The 15 cases with intractable aspiration were treated with cuffed tracheostomy tube with inner cannula and after 2-3 months, 14 of them replaced the cuffed tracheostomy tubes with inner cannula by metal tracheostomy tubes and recovered oral eating, and tracheostomy tubes were no longer required for 12 of 14 patients in following 3-6 months, showing a total decannulation rate of 80% in the patients with refractory aspiration. Conclusion: It was safe and effective to treat aspiration after laryngeal and hypopharyngeal surgery with cuffed tracheostomy tube with inner cannula.

[The national anti-opium-smoking campaigns across the country in the Republican Period].

Anti-opium-smoking had been the key policy of successive central and local governments from the late Qing Dynasty to the Republican Period. Since the establishment of the Nanjing Provisional Government in January 1912, the Anti-opium-smoking campaign had culminated across the country. Under the support of the government, the "National Anti-Opium Association of China" and "Association of Chinese People Rejecting Opium" were established which made an important contribution to China's anti-opium-smoking campaign.Yunnan, Shaanxi, Heilongjiang, Zhejiang, Shanghai and other local governments also combined with local specific circumstances to make anti-opium-smaking policy for punishing severely the opium cultivation, trade and opium smoking, thus, the overrun of opium began to be brought under an overall control.

Integrating Multiple Evidence Sources to Predict Adverse Drug Reactions Based on a Systems Pharmacology Model.

Identifying potential adverse drug reactions (ADRs) is critically important for drug discovery and public health. Here we developed a multiple evidence fusion (MEF) method for the large-scale prediction of drug ADRs that can handle both approved drugs and novel molecules. MEF is based on the similarity reference by collaborative filtering, and integrates multiple similarity measures from various data types, taking advantage of the complementarity in the data. We used MEF to integrate drug-related and ADR-related data from multiple levels, including the network structural data formed by known drug-ADR relationships for predicting likely unknown ADRs. On cross-validation, it obtains high sensitivity and specificity, substantially outperforming existing methods that utilize single or a few data types. We validated our prediction by their overlap with drug-ADR associations that are known in databases. The proposed computational method could be used for complementary hypothesis generation and rapid analysis of potential drug-ADR interactions.

Evaluation of optimal match between gantry rotation time and cardiac cycle on multislice spiral CT coronary angiography imaging.

OBJECTIVE: To evaluate the relationship between gantry rotation time, heart rate and image quality during multislice spiral CT coronary angiography (MSCTCA). PATIENTS AND METHODS: Data of 83 patients who underwent MSCTCA were reviewed. Based on the ratio between cardiac cycle and gantry rotation time, the patients were divided into two groups. Patients whose heart rates fell in the resonance frequency (the cardiac cycle / gantry rotational time ratio of 1.5, 2 or 2.5) ± 2 bpm were classified as synchronous (25 cases), while the remaining 58 patients (included a subgroup of 34 cases in whom heart rates were the same as in synchronous group but who had a different gantry rotation time). comprised the asynchronous group. Image qualities were compared between both groups. RESULTS: In the synchronous group, most (199/287; 69.33%) images were poor. When gantry rotation time was changed in the subgroup of the asynchronous group, the majority (423/442 or 95.70%) of images improved. There was a significant difference (p < 0.001) in the image quality among these patients. In 58 patients from asynchronous group, 757 segments of coronary arteries were evaluated, and 716 segments were of best quality (716/757; 94.58%). CONCLUSIONS: When heart rate and gantry rotation time correlate and synchronous, the so-called frequency harmonics, coronary artery image quality is poor. However, by changing gantry rotation time to avoid the harmonic helps to improve the image quality on MSCTCA. Based on the patient's heart rate, appropriate gantry rotation time can be selected in order to avoid resonance and obtain high quality images.

Influence of cell shape on mechanical properties of Ti-6Al-4V meshes fabricated by electron beam melting method.

Ti-6Al-4V reticulated meshes with different elements (cubic, G7 and rhombic dodecahedron) in Materialise software were fabricated by additive manufacturing using the electron beam melting (EBM) method, and the effects of cell shape on the mechanical properties of these samples were studied. The results showed that these cellular structures with porosities of 88-58% had compressive strength and elastic modulus in the range 10-300MPa and 0.5-15GPa, respectively. The compressive strength and deformation behavior of these meshes were determined by the coupling of the buckling and bending deformation of struts. Meshes that were dominated by buckling deformation showed relatively high collapse strength and were prone to exhibit brittle characteristics in their stress-strain curves. For meshes dominated by bending deformation, the elastic deformation corresponded well to the Gibson-Ashby model. By enhancing the effect of bending deformation, the stress-strain curve characteristics can change from brittle to ductile (the smooth plateau area). Therefore, Ti-6Al-4V cellular solids with high strength, low modulus and desirable deformation behavior could be fabricated through the cell shape design using the EBM technique.

In silico toxicity prediction by support vector machine and SMILES representation-based string kernel.

There is a great need to assess the harmful effects or toxicities of chemicals to which man is exposed. In the present paper, the simplified molecular input line entry specification (SMILES) representation-based string kernel, together with the state-of-the-art support vector machine (SVM) algorithm, were used to classify the toxicity of chemicals from the US Environmental Protection Agency Distributed Structure-Searchable Toxicity (DSSTox) database network. In this method, the molecular structure can be directly encoded by a series of SMILES substrings that represent the presence of some chemical elements and different kinds of chemical bonds (double, triple and stereochemistry) in the molecules. Thus, SMILES string kernel can accurately and directly measure the similarities of molecules by a series of local information hidden in the molecules. Two model validation approaches, five-fold cross-validation and independent validation set, were used for assessing the predictive capability of our developed models. The results obtained indicate that SVM based on the SMILES string kernel can be regarded as a very promising and alternative modelling approach for potential toxicity prediction of chemicals.

Accumulation and acute toxicity of silver in Potamogeton crispus L.

In the present study, Potamogeton crispus L. plants exposed to various concentrations of silver (Ag) (5, 10, 15, and 20 microM) for 5d were investigated to determine the accumulating potential of Ag and its influence on nutrient elements, chlorophyll pigments and fluorescence, various antioxidant enzymes and compounds, adenosine triphosphate (ATP), protein content and ultrastructure. The accumulation of Ag was found to increase in a concentration dependent manner with a maximum of 29.3 microg g(-1) at 20 microM. The nutrient elements (except Ca), photosynthetic pigments, chlorophyll a fluorescence parameters (Fo, Fv, Fv/Fm, Fv/Fo), malondialdehyde (MDA), ATP, peroxidase (POD) activity, ascorbate (AsA), reduced glutathione (GSH) and protein contents decreased significantly as concentration of Ag augmented. In contrast, an induction in SOD activity was recorded, while an initial rise in Ca content and CAT activity was followed by subsequent decline. Morphological symptoms of senescence phenomena such as chlorosis and damage of chloroplasts and mitochondria were observed even at the lowest concentration of Ag, which suggested that Ag hastened the senescence of the tested plants. The loss of nutrients and chlorophyll content and damage of chloroplasts were associated with disturbances in photosynthetic capacity as indicated by the quenching of chlorophyll a fluorescence. Decreased chlorophyll and protein contents suggest oxidative stress induced by Ag. In addition, both the reduction of ATP and the damage to the ultrastructure of organelles were indicative of general disarray in the cellular functions exerted by Ag.

A modified uncorrelated linear discriminant analysis model coupled with recursive feature elimination for the prediction of bioactivity.

To meet the requirements of providing accurate, robust, and interpretable prediction of bioactivity, a modified uncorrelated linear discriminant analysis (M-ULDA) model was developed. In addition, a feature selection method called recursive feature elimination (RFE), originally used for support vector machine (SVM), was introduced and modified to fit the scheme of ULDA. From the evaluation of six pharmaceutical datasets, the M-UDLA coupled with RFE showed better or comparable classification accuracy with respect to other well-studied methods such as SVM and decision trees. The RFE used for ULDA has the advantage of increasing the computational speed and provides useful insights into biochemical mechanisms related to pharmaceutical activity by significantly reducing the number of variables used for the final model.

Prediction of gastro-intestinal absorption using multivariate adaptive regression splines.

Multivariate adaptive regression splines (MARS) and a derived method two-step MARS (TMARS) were used for modelling the gastro-intestinal absorption of 140 drug-like molecules. The published absorption values for these molecules were used as response variable and calculated molecular descriptors as potential explanatory variables. Both methods were compared and their potential use in quantitative structure-activity relationship (QSAR) context evaluated. The predictive abilities of the models were studied using different sequences of Monte Carlo cross validation (MCCV). It was shown that both types of models had good predictive abilities and that for the data used, MARS gave better results than TMARS. It could be concluded that both methods could be valuable for QSAR modelling.

Boosting partial least squares.

A difficulty when applying partial least squares (PLS) in multivariate calibration is that overfitting may occur. This study proposes a novel approach by combining PLS and boosting. The latter is said to be resistant to overfitting. The proposed method, called boosting PLS (BPLS), combines a set of shrunken PLS models, each with only one PLS component. The method is iterative: the models are constructed on the basis of the residuals of the responses that are not explained by previous models. Unlike classical PLS, BPLS does not need to select an adequate number of PLS components to be included in the model. On the other hand, two parameters must be determined: the shrinkage value and the iteration number. Criteria are proposed for these two purposes. BPLS was applied to seven real data sets, and the results demonstrate that it is more resistant than classical PLS to overfitting without loosing accuracy.

Updating multivariate calibrations with the delaunay triangulation method.

Multivariate calibrations must be updated when new samples show different spectral characteristics. In this paper, we discuss how to do this when the calibration is performed with a topological multivariate calibration method based on Delaunay triangulation (DT). The updating leads either to the expansion of the original calibration set or to the creation of a new local model. Outliers in the new samples with respect to the original calibration set are first detected and divided in two groups, namely, marginal outliers, which are considered to be extensions of the calibration set and are used for updating the calibration set, and true outliers. If a sufficient number of true outliers are found to be situated close enough to each other, they can form the basis for a new local model. Several updating simulations performed on a real data set show that the updating procedure performs well. The results for prediction with the DT method after updating are comparable to or better than those after updating with partial least squares (PLS) and it is concluded that, in many cases, the DT method is a valuable alternative for multivariate calibration.

Multivariate adaptive regression splines (MARS) in chromatographic quantitative structure-retention relationship studies.

The multivariate adaptive regression splines (MARS) methodology was applied to build quantitative structure-retention relationships (QSRRs). The response (dependent variable) in the MARS models consisted of the logarithms of the extrapolated retention factors (log k(w)) of 83 structurally diverse drugs on a Unisphere PBD column, using isocratic elutions at pH 11.7. A set of 266 molecular descriptors was used as predictor (independent) variables in the MARS model building. The optimal MARS model uses 34 basis functions to describe the retention and has acceptable predictive properties for new objects. The molecular descriptors included in the model describe hydrophobicity, molecular size, complexity, shape and polarisability. Some additional MARS models were created using alternative strategies. These include models with log P as the single predictor and models obtained with only the three most important molecular descriptors. The use of classification and regression trees (CART) as feature selection technique for predictor variables used in the MARS model was also investigated. Further, it is also studied whether allowing quadratic terms instead of interaction terms might lead to better MARS models.

Classification and regression trees--studies of HIV reverse transcriptase inhibitors.

In this paper, the application of Classification And Regression Trees (CART) is presented for the analysis of biological activity of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). The data consist of the biological activities, expressed as pIC50, of 208 NNRTIs against wild-type HIV virus (HIV-1) and four mutant strains (181C, 103N, 100I, 188L) and the computed interaction energies with the Reverse Transcriptase (RT) binding pocket. CART explains the observed biological activity of NNRTIs in terms of interactions with individual amino acids in the RT binding pocket, i.e., the original data variables.

Determination of total antioxidant capacity in green tea by near-infrared spectroscopy and multivariate calibration.

A principal component regression (PCR) model is built for prediction of total antioxidant capacity in green tea using near-infrared (NIR) spectroscopy. The modelling procedures are systematically studied with the focus on outlier detection. Different outlier detection methods are used and compared. The root mean square error of prediction (RMSEP) of the final model is comparable to the precision of the reference method.

Two novel procedures for automatic resolution of two-way data from coupled chromatography.

In order to deal with the problem of simultaneous qualitative and quantitative analysis of the complicated samples in analytical chemistry, two novel procedures for automatic resolution of two-way data from coupled chromatography were developed in this work. The first can be used to determine automatically the number of components involved in a certain peak cluster. The second method is an iterative resolution procedure named the stepwise key spectrum selection which has also been developed to resolve automatically the spectra and chromatographic profiles of every component in the peak cluster investigated. The results obtained from simulated and real data show that the proposed methods perform fairly well.

Gas chromatography-mass spectrometry and chemometric resolution applied to the determination of essential oils in Cortex cinnamomi.

In this paper, a novel procedure for qualitative and quantitative analysis of the two-dimensional data obtained from GC-MS is investigated to determine chemical components of essential oils in Cortex Cinnamomi from four different producing areas. A new method named iterative optimization procedure (IOP) specially used to resolve embedded peaks is also developed. With the help of IOP and other chemometric techniques, such as heuristic evolving latent projections, evolving factor analysis, sub-window factor analysis and orthogonal projection resolution, and etc., the detection of the purity of chromatographic peaks can be first addressed, and then the overlapping peaks are resolved into the pure chromatogram and mass spectrum of each component. The similarity searches in the MS database are finally conducted to qualitatively determine the chemical components. The results obtained showed that the accuracy of qualitative and quantitative analysis could be greatly enhanced by chemometric resolution methods. The chemometric resolution techniques upon the two-dimensional data can be quite promising tools for the analysis of the complex samples like traditional Chinese medicine.

Inhibition of gastric mucin synthesis by Helicobacter pylori.

BACKGROUND & AIMS: Mucins are high-molecular-weight glycoproteins that protect the gastric epithelium. Previous data suggested that gastric surface-type mucin is decreased in Helicobacter pylori-infected patients and restored after eradication of the infection. Our aim was to determine the effect of H. pylori on mucin synthesis in cultured gastric epithelial cells. METHODS: Mucin synthesis was measured by labeling with [(3)H]glucosamine and size-exclusion chromatography. Expression of MUC5AC and MUC1 mucin protein antigens was quantitated by Western blot analysis. RESULTS: Mucin synthesis was inhibited more than 80% when KATO III cells were incubated with H. pylori, with no effect on mucin secretion or degradation. Inhibition was rapid (4 hours), partially reversible, dependent on concentration of bacteria, and associated with the insoluble membrane fraction. H. pylori decreased levels of MUC5AC and MUC1 mucins. MUC1 inhibition was half-maximal by 4 hours and partially reversed by 24 hours, but the decrease in MUC5AC was less rapid and not reversible within 24 hours. CONCLUSIONS: H. pylori inhibits total mucin synthesis in vitro and decreases the expression of MUC5AC and MUC1. A decrease in gastric mucin synthesis in vivo may disrupt the protective surface mucin layer.