Effect of YKL-40 RNA Interference on VEGF Gene Polymorphism Expression in Atherosclerotic Mice

Aims: To investigate the effect of YKL-40 RNA interference on VEGF gene polymorphism expression in atherosclerotic mice. Methods: After the atherosclerosis models in mice were built, the mice were divided into three groups including control group, negative control group and observation group, which were separately given to normal saline, negative virus (5 × 107 TU) and YKL-40 RNA interference lentivirus. Then the whole blood DNA was extracted and genotyped in each group of mice and the expression of VEGF in each group of mice was detected by PCR, while the expression level of inflammatory factors in each group of mice was detected by ELISA. Meanwhile, the aortas of mice in each group were pathologically analyzed and the atherosclerosis of mice was detected. Results: Compared with the control group, the VEGF content in both the virus negative control group and the observation group was significantly increased（P<0.05）. The detection rates of CC genotype and C allele at rs699947 of VEGF gene in the observation group were significantly higher than those in the control group and the virus negative control group, and the difference was statistically significant. There were no significant changes for the expression of HDL-C, LDL-C, TC and TG in mice of each group（P>0.05）. Moreover, the levels of Lp-PLA2 and MCP-1 in the negative control group were significantly increased (P < 0.05), while those in the observation group were significantly decreased (P < 0.05) compared to that in control group. What’s more, the histomorphology of the observation group was significantly different from that of the control group and the virus negative control group. The thickness of the fibrous cap of the as plaque was significantly higher than that of the control group and the virus negative control group, but the plaque area and fat content were significantly lower than that of the control group and the virus negative control group and the NC group. Besides, there was no significant difference in lipid content, fiber cap thickness and plaque area between the control group and the virus negative control group. Conclusion: YKL-40 RNAi could improve the VEGF polymorphism, reduce the expression of LPâƒPLA2 and MCPâƒ1, and significantly inhibit the occurrence and development of atherosclerosis, which was expected to provide a new target for the prevention and treatment of atherosclerosis

Genetic Polymorphisms in CYP2E1: Association with Schizophrenia Susceptibility and Risperidone Response in the Chinese Han Population

CYP2E1 is a member of the cytochrome P450 superfamily, which is involved in the metabolism and activation of both endobiotics and xenobiotics. The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number NC_000010.10) are reported to be related to the development of several mental diseases and to be involved in the clinical efficacy of some psychiatric medications. We investigated the possible association of CYP2E1 polymorphisms with susceptibility to schizophrenia in the Chinese Han Population as well as the relationship with response to risperidone in schizophrenia patients.In a case-control study, we identified 11 polymorphisms in the 5' flanking region of CYP2E1 in 228 schizophrenia patients and 384 healthy controls of Chinese Han origin. From among the cases, we chose 130 patients who had undergone 8 weeks of risperidone monotherapy to examine the relationship between their response to risperidone and CYP2E1 polymorphisms. Clinical efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS).Statistically significant differences in allele or genotype frequencies were found between cases and controls at rs8192766 (genotype p = 0.0048, permutation p = 0.0483) and rs2070673 (allele: p = 0.0018, permutation p = 0.0199, OR = 1.4528 95%CI = 1.1487-1.8374; genotype: p = 0.0020, permutation p = 0.0225). In addition, a GTCAC haplotype containing 5 SNPs (rs3813867, rs2031920, rs2031921, rs3813870 and rs2031922) was observed to be significantly associated with schizophrenia (p = 7.47E-12, permutation p<0.0001). However, no association was found between CYP2E1 polymorphisms/haplotypes and risperidone response.Our results suggest that CYP2E1 may be a potential risk gene for schizophrenia in the Chinese Han population. However, polymorphisms of the CYP2E1 gene may not contribute significantly to individual differences in the therapeutic efficacy of risperidone. Further studies in larger groups are warranted to confirm our results

Effect of the clinical decision assessment system on clinical outcomes of delirium in hospitalized older adults: study protocol for a pair-matched, parallel, cluster randomized controlled superiority trial

Abstract Background Prompt recognition of delirium is the first key step in its proper management. A previous study has demonstrated that nurses’ delirium screening using the usual paper version assessment tool has no effect on clinical outcomes. Clinical decision assessment systems have been demonstrated to improve patients’ adherence and clinical outcomes. Therefore, We developed a clinical decision assessment system (3D-DST) based on the usual paper version (3-min diagnostic interview for CAM-defined delirium), which was developed for assessing delirium in older adults with high usability and accuracy. However, no high quality evidence exists on the effectiveness of a 3D-DST in improving outcomes of older adults compared to the usual paper version. Methods A pair-matched, open-label, parallel, cluster randomized controlled superiority trial following the SPIRIT checklist. Older patients aged 65 years or older admitted to four medical wards of a geriatric hospital will be invited to participate in the study. Prior to the study, delirium prevention and treatment interventions will be delivered to nurses in both the intervention and control groups. The nurses in the intervention group will perform routine delirium assessments on the included older patients with 3D-DST, while the nurses in the control group will perform daily delirium assessments with the usual paper version. Enrolled patients will be assessed twice daily for delirium by a nurse researcher using 3D-DST. The primary outcome is delirium duration. The secondary outcomes are delirium severity, incidence of delirium, length of stay, in-hospital mortality, adherence to delirium assessment, prevention, and treatment of medical staff. Discussion This study will incorporate the 3D-DST into clinical practice for delirium assessment. If our study will demonstrate that 3D-DST will improve adherence with delirium assessment and clinical outcomes in older patients, it will provide important evidence for the management of delirium in the future. Trial registration Chinese Clinical Trial Registry, Identifier: ChiCTR1900028402. https://www.chictr.org.cn/showproj.aspx?proj=47127 . Protocol version: 1, 29/7/22

Optimal Randomness for Stochastic Configuration Network (SCN) with Heavy-Tailed Distributions.

Stochastic Configuration Network (SCN) has a powerful capability for regression and classification analysis. Traditionally, it is quite challenging to correctly determine an appropriate architecture for a neural network so that the trained model can achieve excellent performance for both learning and generalization. Compared with the known randomized learning algorithms for single hidden layer feed-forward neural networks, such as Randomized Radial Basis Function (RBF) Networks and Random Vector Functional-link (RVFL), the SCN randomly assigns the input weights and biases of the hidden nodes in a supervisory mechanism. Since the parameters in the hidden layers are randomly generated in uniform distribution, hypothetically, there is optimal randomness. Heavy-tailed distribution has shown optimal randomness in an unknown environment for finding some targets. Therefore, in this research, the authors used heavy-tailed distributions to randomly initialize weights and biases to see if the new SCN models can achieve better performance than the original SCN. Heavy-tailed distributions, such as Lévy distribution, Cauchy distribution, and Weibull distribution, have been used. Since some mixed distributions show heavy-tailed properties, the mixed Gaussian and Laplace distributions were also studied in this research work. Experimental results showed improved performance for SCN with heavy-tailed distributions. For the regression model, SCN-Lévy, SCN-Mixture, SCN-Cauchy, and SCN-Weibull used less hidden nodes to achieve similar performance with SCN. For the classification model, SCN-Mixture, SCN-Lévy, and SCN-Cauchy have higher test accuracy of 91.5%, 91.7% and 92.4%, respectively. Both are higher than the test accuracy of the original SCN

Study on Soil-Water Characteristics of Expansive Soil under the Dry-Wet Cycle and Freeze-Thaw Cycle considering Volumetric Strain

This paper targets the expansive soils in Heilongjiang and Ankang to explore the influence of initial dry density, dry-wet cycle, and freeze-thaw cycle on the soil-water characteristics. The centrifuge method was used to obtain the soil-water characteristic curves (SWCCs) with different conditions. The volumetric strain of SWCC was modified based on the shrinkage test, and the corresponding fitting equations considering different factors were established. The results show that the volumetric water content is modified to consider the volume shrinkage effect of expansive soil, and the modification is more obvious in the high matric suction range. The smaller the initial dry density is, the worse the water-holding capacity of the sample is, and the smaller the air intake value is. The greater the time of the dry-wet cycle is, the greater the saturated volumetric water content of the sample is, and the corresponding water-holding capacity is significantly reduced. When the dry-wet cycle increases to a certain extent, the structure becomes stable. With the increase of the freeze-thaw cycle, the saturated volumetric water content first decreases and then increases. Similarly, after several times of the freeze-thaw cycle, the structure is basically stable. The fitted Gardner model equations under different conditions were proved to be able to describe the SWCCs of the two targeted expansive soils

Association between Phosphatase Related Gene Variants and Coronary Artery Disease: Case-Control Study and Meta-Analysis

Recent studies showed that the serum alkaline phosphatase is an independent predictor of the coronary artery disease (CAD). In this work, we aimed to summarize the association between three phosphatase related single nucleotide polymorphisms (rs12526453, rs11066301 and rs3828329) and the risk of CAD in Han Chinese. Our results showed that the rs3828329 of the ACP1 gene was closely related to the risk of CAD in Han Chinese (OR = 1.45, p = 0.0006). This significant association of rs3828329 with CAD was only found in the females (Additive model: OR = 1.80, p = 0.001; dominant model: OR = 1.69, p = 0.03; recessive model: OR = 1.96, p = 0.0008). Moreover, rs3828329 was likely to exert its effect in females aged 65 years and older (OR = 2.27, p = 0.001). Further meta-analyses showed that the rs12526453 of PHACTR11 gene (OR = 1.14, p &lt; 0.0001, random-effect method) and the rs11066301 of PTPN11 gene (OR = 1.15, p &lt; 0.0001, fixed-effects method) were associated with CAD risk in multiple populations. Our results showed that the polymorphisms rs12526453 and rs11066301 are significantly associated with the CAD risk in multiple populations. The rs3828329 of ACP1 gene is also a risk factor of CAD in Han Chinese females aged 65 years and older

Synchronous Vibration Measurements for Shrouded Blades Based on Fiber Optical Sensors with Lenses in a Steam Turbine

It is important to obtain accurate dynamic vibrations of steam turbine blades for safe operation. Strain gauge (SG) measurements cannot fully obtain vibrations of all blades and nodal diameter (ND) details. The blade tip timing (BTT) technique could resolve this problem because it has the advantage of measuring all blades&rsquo; vibrations. This article proposed an improved BTT technique for measuring synchronous vibrations of shrouded blades in a steam turbine based on fiber optical sensors with lenses. The newly developed sensor was equipped with a Plano-convex lens, and the optical path was specifically designed to collimate the beam within a large working distance from 4 to 19 mm and improve the measuring accuracy. A method to search the spectra of all peak vibration amplitudes of all the blades was proposed to obtain the ND details of synchronous vibration. Experimental results validated the efficiency and accuracy of the proposed methods and sensors. Comparison results of BTT measurements with SG measurements showed that the relative errors of normalized frequency and strain were small and acceptable

Engineered FGF19ΔKLB protects against intrahepatic cholestatic liver injury in ANIT-induced and Mdr2-/- mice model

Abstract Background The major safety concern of the clinical application of wild type FGF19 (FGF19WT) emerges given that its extended treatment causes hepatocellular carcinoma. Therefore, we previously generated a safer FGF19 variant - FGF19ΔKLB, which have same effects on glycemic control and bile acid production but much less mitogenic activity. However, it remains unclear as to whether FGF19ΔKLB ameliorates intrahepatic cholestasis. Results We found that, similar to that of FGF19WT, the chronic administration of FGF19ΔKLB protects mice from cholestatic liver injury in these two models. The therapeutic benefits of FGF19ΔKLB on cholestatic liver damage are attributable, according to the following mechanistic investigation, to the reduction of BA production, liver inflammation, and fibrosis. More importantly, FGF19ΔKLB did not induce any tumorigenesis effects during its prolonged treatment. Conclusions Together, our findings raise hope that FGF19ΔKLB may represent a useful therapeutic strategy for the treatment of intrahepatic cholestasis