Anticoagulant effects of Rivaroxaban after surgical fixation of spinal fracture.

In recent years, the concept of treatment after surgery in the department of orthopedics has changed from hemostasis to anticoagulant. This article analyses the safety and effectiveness of anticoagulants for prophylactic anticoagulants after spinal fractures. By analyzing the incidence of bleeding and VTE in 2 weeks after operation, there was no significant difference between the 2 groups (P>0.05), but the incidence of VTE in rivaroxaban group was significantly lower than that in control group. In conclusion, the rivaroxaban oral anticoagulants are stable, safe and easy to use. It significantly reduced the incidence of VTE after spinal fracture and nerve injury, and did not increase the risk of bleeding. It is an ideal type of prophylactic anticoagulant after the operation of spinal fracture, which is worthy of further clinical study.

Mediating effects of attitude on the relationship between knowledge and willingness to organ donation among nursing students.

Background: The current rate of organ donation in China falls significantly below the global average and the actual demand. Nursing students play a crucial role in supporting and promoting social and public welfare activities. This study primary aims to analyze the levels of knowledge, attitudes, willingness toward organ donation, and attitudes toward death among nursing students, and investigate the mediating role of attitude in the relationship between knowledge and willingness. The secondary aims to identify factors that may influence the willingness. Methods: A convenience sample of nursing students completed online-administered questionnaires measuring the level of knowledge, attitudes, and willingness toward organ donation before and after clinical internship. Spearman correlation and mediation analyses were used for data analyses. Results: Before the clinical internship, there were 435 nursing students who had not yet obtained their degrees and were completing their clinical internships. After the internship, this number decreased to 323. The mean score for knowledge before and after the clinical internship (7.17 before and 7.22 after, with no significant difference), the attitude (4.58 before and 4.36 after, with significant difference), the willingness (12.41% before and 8.67% after, with significant difference), the Death Attitude Profile-Revised (DAP-R) score (94.41 before and 92.56 after, with significant difference). The knowledge indirectly affected nursing students' willingness to organ donation through attitude. Knowledge had a direct and positive impact on attitudes (ß = 1.564). Additionally, nursing students' attitudes positively affected their willingness (ß = 0.023). Attitudes played a mediating role in the relationship between knowledge and willingness (ß = 0.035). Additionally, attitude toward death, fear of death, and acceptance of the concept of escape were found to be correlated with their willingness. Conclusion: Organ donation willingness was found to be low among nursing students. Positive attitudes were identified as a mediating factor between knowledge and willingness. Additionally, DAP-R was a related factor. Therefore, it is recommended to focus on improving knowledge and attitude, as well as providing death education to help nursing students establish a positive attitude toward death. These efforts can contribute to the promotion of organ donation.

Anti-inflammatory role of fenofibrate in treating diseases.

Inflammation contributes to the pathogenesis of several diseases. Fenofibrate, known as a peroxisome proliferator-activated receptor - α (PPAR-α) agonist, is a classic drug for treating hyperlipidemia. In addition to its lipid-lowering effect, fenofibrate has also been reported to exert anti-inflammatory effects with complicated underlying mechanisms of action. In general, the anti-inflammatory effect of fenofibrate is secondary to its lipid-lowering effect, especially for the inflammation caused by hyperlipidemia in the circulatory system. Some anti-inflammatory actions may also come from its regulatory effects on intracellular lipid metabolism by activating PPAR-α. In addition, some roles in anti-inflammation might be mediated by its direct regulation of inflammatory signaling pathways. In order to understand anti-inflammatory activities and the underlying mechanisms of fenofibrate action in disease better, we herein reviewed and discussed the anti-inflammatory roles and its subserving mechanisms in various diseases of different organ systems. Thus, this review offers insights into the optimal use of fenofibrate in the clinical setting.

Reduction of NADPH oxidase 4 in adipocytes contributes to the anti-obesity effect of dihydroartemisinin.

Artemisinin derivatives have been found to have anti-obesity effects recently, but the mechanism is still controversial. Herein, long-term DHA treatment in obese mice significantly reduced the body weight and improved glucose metabolism. However, short-term DHA treatment did not affect glucose metabolism in obese mice, suggesting that the improved glucose metabolism in mice with DHA treatment could be secondary to body weight reduction. Consistent with previous reports, we observed that DHA inhibited the differentiation of adipocytes. Mechanistically, DHA significantly reduced the expression of NADPH oxidase 4 (NOX4) in white adipose tissue (WAT) of mice and differentiated adipocytes, and using NOX4 siRNA or the NOX4 inhibitor GKT137831 significantly attenuated adipocyte differentiation. Over-expression of NOX4 partially reversed the inhibition effect of DHA on adipogenic differentiation of preadipocytes. In addition, targeted proteomics analysis showed that DHA improved the abnormality of metabolic pathways. In conclusion, DHA significantly reduced fat mass and improved glucose metabolism in obese mice, possibly by inhibiting NOX4 expression to suppress adipocyte differentiation and lipid accumulation in adipocytes.

DL-CNV: A deep learning method for identifying copy number variations based on next generation target sequencing.

Copy number variations (CNVs) play an important role in many types of cancer. With the rapid development of next generation sequencing (NGS) techniques, many methods for detecting CNVs of a single sample have emerged: (i) require genome-wide data of both case and control samples, (ii) depend on sequencing depth and GC content correction algorithm, (iii) rely on statistical models built on CNV positive and negative sample datasets. These make them costly in the data analysis and ineffective in the targeted sequencing data. In this study, we developed a novel alignment-free method called DL-CNV to call CNV from the target sequencing data of a single sample. Specifically, we collected two sets of samples. The first set consists of 1301 samples, in which 272 have CNVs in ERBB2 and the second set is composed of 1148 samples with 63 samples containing CNVs in MET. Finally, we found that a testing AUC of 0.9454 for ERBB2 and 0.9220 for MET. Furthermore, we hope to make the CNV detection could be more accurate with clinical "gold standard" (e.g. FISH) information and provide a new research direction, which can be used as the supplement to the existing NGS methods.

Identification of Risk Pathways and Functional Modules for Coronary Artery Disease Based on Genome-wide SNP Data.

Coronary artery disease (CAD) is a complex human disease, involving multiple genes and their nonlinear interactions, which often act in a modular fashion. Genome-wide single nucleotide polymorphism (SNP) profiling provides an effective technique to unravel these underlying genetic interplays or their functional involvements for CAD. This study aimed to identify the susceptible pathways and modules for CAD based on SNP omics. First, the Wellcome Trust Case Control Consortium (WTCCC) SNP datasets of CAD and control samples were used to assess the joint effect of multiple genetic variants at the pathway level, using logistic kernel machine regression model. Then, an expanded genetic network was constructed by integrating statistical gene-gene interactions involved in these susceptible pathways with their protein-protein interaction (PPI) knowledge. Finally, risk functional modules were identified by decomposition of the network. Of 276 KEGG pathways analyzed, 6 pathways were found to have a significant effect on CAD. Other than glycerolipid metabolism, glycosaminoglycan biosynthesis, and cardiac muscle contraction pathways, three pathways related to other diseases were also revealed, including Alzheimer's disease, non-alcoholic fatty liver disease, and Huntington's disease. A genetic epistatic network of 95 genes was further constructed using the abovementioned integrative approach. Of 10 functional modules derived from the network, 6 have been annotated to phospholipase C activity and cell adhesion molecule binding, which also have known functional involvement in Alzheimer's disease. These findings indicate an overlap of the underlying molecular mechanisms between CAD and Alzheimer's disease, thus providing new insights into the molecular basis for CAD and its molecular relationships with other diseases.

Pathway-based analysis tools for complex diseases: a review.

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods-the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases.

Expression of Toll-like receptor 4 on peripheral blood mononuclear cells and its effects on patients with acute myocardial infarction treated with thrombolysis.

BACKGROUND AND AIMS: TLR4 has been shown to mediate inflammation in animal models of myocardial ischemia/reperfusion injury (MI/RI). Here we hypothesized that TLR4 on peripheral blood mononuclear cells (PBMCs) may be involved in the inflammatory response in this type of clinical event. METHODS: Seventy two patients with acute myocardial infarction (AMI) who underwent thrombolysis were assigned into reperfusion group (n = 43) and non-reperfusion group (n = 29) according to recanalization of infarct-related artery (IRA) and 40 healthy volunteers were enrolled in this experiment. Eight mL of venous blood was taken from all patients 0 h before and 2, 6, 12, and 24 h after thrombolysis. Flow cytometry (FCM) was used to detect TLR4 protein expression and real-time quantitative RT-PCR was performed to determine TLR4 mRNA and myeloid differentiation protein-88 (Myd88) mRNA expression. The concentration of tumor necrosis factor-α (TNF-α) in plasma was evaluated using enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with controls, all detected indicators in AMI patients were upregulated before thrombolysis (p <0.01). After thrombolysis, they were further increased. In reperfusion group, all attained their peaks in earlier hours and the peak values were lower compared with non-reperfusion group. In both cases, either reperfusion or non-perfusion, TLR4 mRNA expression was positively correlated with the levels of Myd88 mRNA (r = 0.886 and 0.694, p <0.01), respectively. CONCLUSIONS: TLR4 expression on PBMCs was markedly elevated in AMI patients either reperfused or non-reperfused. Inflammatory reaction by activated TLR4 in MI/RI in patients may be through TLR4-Myd88-dependent signal pathway.