Coronary heart disease (CHD) is a typical cardiovascular disease whose occurrence and development is a long process. Timely and accurate diagnosis of patients with varying degrees of coronary artery stenosis (VDCAS) is conducive to accurate treatment and prognosis assessment. This study aims to correctly classify VDCAS patients by utilizing multi-domain features fusion of single-lead 5-min ECG signals and machine learning methods, so as to provide reference for doctors to judge the CHD development process. ECG signals were collected from 206 subjects with CHD, mild CHD, thoracalgia and normal coronary angiograms (TNCA), and healthy. Then, the time, frequency, time–frequency, and nonlinear domain features of ECG signals were extracted to establish a multi-domain feature set. To get the optimum subset of features, the recursive feature elimination (RFE) and information gain (IG) were selected. Subsequently, eXtreme Gradient Boosting (XGBoost) and random forest (RF) were adopted for classification. Results indicated that RFE combined with XGBoost was significantly effective in classifying VDCAS patients. When the four categories of subjects (CHD, mild CHD, TNCA, and healthy) were classified, the average accuracy, sensitivity, specificity, and F1-score of the proposed method were 91.74%, 89.39%, 96.80%, and 90.09%, respectively. Besides, three categories of subjects (no stenosis, luminal narrowing [Formula: see text] 50%, and luminal narrowing [Formula: see text] 50%) and two categories of subjects (CHD and healthy) were also analyzed, and the average accuracy was 91.27% and 98.46%, respectively. The results suggest that the proposed method can provide reference for doctors to judge VDCAS patients.
Dehydroeffusol is a naturally occurring phenanthrene isolated from Juncus effusus. In the context of screening new drugs against gastrointestinal spasms, we investigated its effects on isolated rat jejunum in vitro. Dehydroeffusol (30–90 µM) slightly and transiently enhanced contractions in a concentration-dependent manner but significantly inhibited the contractions induced by KCl (100 mM), (±)-Bay-K8644 (5 µM), pilocarpine (90 µM), and histamine (100 µM). These results show that dehydroeffusol may antagonize the spasmogenic activity of various agents, and therefore, could be a promising agent in the treatment of spasms. Its potential spasmolytic mechanism is also discussed.
Traditional Chinese Medicine (TCM) has received increasing attention as a complementary approach or alternative to modern medicine. However, experimental methods for identifying novel targets of TCM herbs heavily relied on the current available herb-compound-target relationships. In this work, we present an Herb-Target Interaction Network (HTINet) approach, a novel network integration pipeline for herb-target prediction mainly relying on the symptom related associations. HTINet focuses on capturing the low-dimensional feature vectors for both herbs and proteins by network embedding, which incorporate the topological properties of nodes across multi-layered heterogeneous network, and then performs supervised learning based on these low-dimensional feature representations. HTINet obtains performance improvement over a well-established random walk based herb-target prediction method. Furthermore, we have manually validated several predicted herb-target interactions from independent literatures. These results indicate that HTINet can be used to integrate heterogeneous information to predict novel herb-target interactions.
Autogenous bone graft is the preferred method for the reconstruction of maxillofacial defects. As an additional choice, the aim of this study was to develop and test the application of individual digital planning, rapid prototyping titanium implants, and functional long-term results in the reconstruction of traumatic zygomatico-orbital defects. Six patients were treated with 3-dimensional digital surgery designs, digital locating template, and individually fabricated titanium implants. All patients were followed for a minimum of 18 months with a mean of 51.8 months. The recovery of facial contour and function was satisfactory in 4 patients. In the other 2 patients, 1 implant was removed after implant exposure caused by infection, and the other implant was removed because of persistent diplopia. Although the risk of implant exposure exists, individual digital planning procedures, rapid prototyping, digital locating templates, and titanium implants are still effective methods for reconstructing traumatic zygomatico-orbital defects. We believe that the appropriate choice of surgical cases is of great importance when using individually designed titanium implants to restore maxillofacial defects. The patient's age, health, medical history, local infection, location and extent of the bony defect, and remaining soft tissue volume should all be taken into consideration.
Anti-cardiac fibrosis (CF) is one of the key therapeutic strategies for the treatment of various heart diseases. Therefore, development of drugs targeting CF is promising. However, there are very few studies that systemically explore effective drugs for CF. It has been known that many natural compounds display antifibrosis effects. In this work, we aim to build an integrated model for systematic pursuit of anti-CF agents from natural compounds. We first constructed a heart-specific CF marker-gene-centered functional gene module (HCFM) that represents a set of genes specifically involved in CF based on the CF marker genes and known gene coexpression knowledge. Then, we extracted transcriptional data induced by natural compounds from the Gene Expression Omnibus database. The anti-CF effects of compounds were evaluated by the correlation of HCFM in the compound-induced gene expression profiles by gene set enrichment analysis. Finally, the anti-CF effect of a top-predicted natural monomer, schisantherin A, was experimentally validated in the myocardial infarction animal model. This strategy integrating different types of technologies is expected to help create new opportunities for development of drugs targeting CF.
Modern medicine often clashes with traditional medicine such as Chinese herbal medicine because of the little understanding of the underlying mechanisms of action of the herbs. In an effort to promote integration of both sides and to accelerate the drug discovery from herbal medicines, an efficient systems pharmacology platform that represents ideal information convergence of pharmacochemistry, ADME properties, drug-likeness, drug targets, associated diseases and interaction networks, are urgently needed.The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) was built based on the framework of systems pharmacology for herbal medicines. It consists of all the 499 Chinese herbs registered in the Chinese pharmacopoeia with 29,384 ingredients, 3,311 targets and 837 associated diseases. Twelve important ADME-related properties like human oral bioavailability, half-life, drug-likeness, Caco-2 permeability, blood-brain barrier and Lipinski's rule of five are provided for drug screening and evaluation. TCMSP also provides drug targets and diseases of each active compound, which can automatically establish the compound-target and target-disease networks that let users view and analyze the drug action mechanisms. It is designed to fuel the development of herbal medicines and to promote integration of modern medicine and traditional medicine for drug discovery and development.The particular strengths of TCMSP are the composition of the large number of herbal entries, and the ability to identify drug-target networks and drug-disease networks, which will help revealing the mechanisms of action of Chinese herbs, uncovering the nature of TCM theory and developing new herb-oriented drugs. TCMSP is freely available at http://sm.nwsuaf.edu.cn/lsp/tcmsp.php.
A 66-year-old female patient received oral sertraline (initial dose 25 mg once daily, gradually increased to 100 mg once daily on day 10), zopiclone (7.5 mg once per night), lorazepam (0.5 mg thrice daily), and amlodipine (2.5 mg once daily) following the doctor′s advice due to recurrent depressive disorder, sleep disorder, and hypertension. Before administration, the patient′s serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (γ-GT) were 21 U/L, 16 U/L and 50 U/L, respectively. On day 16 after the medication, the patient′s serum levels of AST, ALT, and γ-GT were 114 U/L, 134 U/L, and 192 U/L, respectively, but the treatment protocol was not adjusted. On day 21 after the medication, her serum levels of AST, ALT, and γ-GT turned to be 178 U/L, 242 U/L, and 362 U/L, respectively. Then hepatoprotective drugs were given, sertraline was discontinued by gradual reduction (oral escitalopram 5 mg once daily was added when sertraline was reduced to 25 mg once daily, but escitalopram was changed to oral mirtazapine 15 mg at bedtime finally due to the patient′s leg discomfort), and the other drugs were continued. The liver function of the patient gradually improved and her serum levels of AST, ALT, and γ-GT were 35 U/L, 36 U/L, and 108 U/L, respectively about 50 days after sertraline withdrawal.
Key words:
Sertraline; Drug-related side effects and adverse reactions; Liver diseases
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