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Objective. Yikunyin is an empirical prescription that exhibits good efficacy in the clinical treatment of menopausal syndrome; however, its underlying mechanism remains unclear. This study investigates the mechanism implicated in the therapeutic effect of Yikunyin by identifying its hub genes, central pathways, and key active ingredients. Method. The active ingredients and targets of Yikunyin were obtained from the Traditional Chinese Medicine Systems Pharmacology database, whereas the targets related to menopausal syndrome were obtained from GeneCards, PharmGKB, Therapeutic Target Database (TTD), and Comparative Toxicogenomics Database (CTD). To reveal the pharmacological mechanism, the component-target and the intersecting protein-protein interaction (PPI) networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Finally, molecular docking was carried out to assess the strength of binding between the key active ingredients and key targets. Results. A total of 418 targets and 121 active ingredients were identified in Yikunyin. The intersection of Yikunyin’s 418 targets with the 2822 targets related to menopausal syndrome shows that there are 247 common targets that can be considered potential targets of Yikunyin in the treatment of menopausal syndrome. The topology analysis of the constructed PPI network conducted using the Cytoscape software shows that there are 15 hub genes implicated in the therapeutic effect of Yikunyin: AKT1, PRKCA, TLR9, CXCL10, PRKCD, PARP1, ABCB1, TP53, CAV1, MAPK8, PPARA, GRB2, EGFR, IL-6, and JAK2. Moreover, the key active components acting on these genes are paeoniflorin, luteolin, quercetin, beta-sitosterol, and kaempferol. GO and KEGG analyses indicate that Yikunyin can treat menopausal syndrome by regulating cellular response to chemical stress (GO:0062197), cellular response to oxidative stress (GO:0034599), phosphatase binding (GO:0019902), cytokine receptor binding (GO:0005126), PI3K-Akt signaling (hsa04151), lipid and atherosclerosis (hsa05417), and hepatitis B (hsa05161). Finally, the results of molecular docking suggest that the key active ingredients and key targets can bind well, with binding energies of less than −5 kJ/mol. Conclusion. The research conducted herein reveals that Yikunyin treats menopausal syndrome by targeting AKT1 and IL-6 and by regulating the PI3K-Akt signaling pathway. Moreover, it provides a new idea for understanding the therapeutic effects of traditional Chinese medicines.

Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.

© 2019 IEEE. Endoscopic vision plays a significant role in minimally invasive surgical procedures. The visibility and maintenance of such direct in situ vision is paramount not only for safety by preventing inadvertent injury but also to improve precision and reduce operating time. Unfortunately, the endoscopic vision is unavoidably degraded due to the illumination variations during surgery. This paper aims to restore or augment such degraded visualization and quantitatively evaluate it during robotic surgery. A multiscale bilateral-weighted retinex method is proposed to remove non-uniform and highly directional illumination and enhance surgical vision, while an objective no-reference image visibility assessment method is defined in terms of sharpness, naturalness, and contrast, to quantitatively and objectively evaluate the endoscopic visualization on surgical video sequences. The methods were validated on surgical data, with the experimental results showing that our method outperforms existent retinex approaches. In particular, the combined visibility was improved from 0.81 to 1.06, while three surgeons generally agreed that the results were restored with much better visibility.

A risk monitoring method based on normal region estimation (NRE) is systematically proposed for the actual situation of the lack of fault data in the condition identification and monitoring of rail...

Introduction Standard bi-level non-invasive ventilation with fixed-level pressure support (PS) delivery may not maintain ventilation during the changes in pulmonary mechanics that occur throughout day and night, so average volume-assured pressure support (AVAPS) modes that target a preset volume by adjustment of PS may be effective. Objective Our meta-analysis wants to compare AVAPS and pressure support non-invasive ventilation (PS-NIV) regarding arterial blood gases (ABGs), sleep efficiency and compliance. Method Relevant publications indexed in PubMed, Cochrane Library, Embase, Web of Science, Wanfang Data, China National Knowledge Infrastructure and VIPI were identified. Appropriate articles identified from the reference lists of the above searches were also reviewed. We included randomized controlled trials involved the use of AVAPS and PS-NIV ventilation for chronic respiratory failure. Each included study weighted mean differences, and 95% confidence intervals (CI) were calculated for continuous outcomes. Statistical heterogeneity was assessed using the I2 value ≤ 50% were considered as no statistical heterogeneity and used fixed effects model. Otherwise, a random effects model was used. Results Eight trials were eligible. No significant difference was observed between AVAPS and PS-NIV groups to compare PaCO2 (OR -0.97, CI-2.54-0.61, P = 0.23) and PaO2 (OR -1.81, CI-4.29-0.67, P = 0.15) in ABGs. There was no significant difference between the two groups with sleep efficiency (OR -3.31, CI-7.58-0.95, P = 0.13) and visual analog scale (OR 0.32, CI-6.97-7.61, P = 0.93). Conclusions The evidence shows there is no significant difference in clinical outcomes when comparing AVAPS and PS-NIV used for chronic respiratory failure patients.

Collecting and summarizing human use experience(HUE) data, forming high-quality data and evidences that can be used for evaluation are the key links of HUE research on traditional Chinese medicine(TCM). The collection, collation and summary of human experience data were discussed in this paper. It is pointed out that the collection of HUE should be focus on the source of prescription of new traditional Chinese medicines, and be summarized based on dialectical thinking, experience in medication, characte-ristics of prescription and clinical application. The collected contents include prescription, process, clinical location and applicable population, efficacy data and safety data, etc. The methods include interview, clinical data summary and data mining. When the data formed based on HUE information is used as drug registration information, it is necessary to ensure that the data source is legal and compliant, and the ownership of intellectual property is clear.Data sources should meet the requirements of medical ethics. To avoid conflict of interest, data analysis should be conducted by an independent third party. It is necessary to develop the quality control measures of HUE data to ensure the data traceability, integrity, consistency and accuracy, and avoid data bias.The data of HUE should include the key data such as accurate clinical location and applicable population, recognized clinical efficacy and safety.After the formation of HUE, the statistical analysis plan of empirical data of human use should be formulated. Through strict data processing, statistical analysis and clinical interpretation, HUE can be produced for evaluation.

This article proposes that the research and development of new Chinese medicines should be based on the clinical values of traditional Chinese medicine(TCM), and expounds the multiple clinical values of new Chinese medicines such as therapeutic effects, adjuvant treatment effects, improvement of disease symptoms, improvement of quality of life, prevention of diseases, etc., so as to broaden the clinical indications of new Chinese medicines. It is pointed out that the clinical value of TCM determines the clinical efficacy evaluation method of new Chinese medicines, so as to construct a clinical evaluation system of new Chinese medicines with the characteristics of TCM. It is proposed that the clinical value of new Chinese medicines should be found under the guidance of TCM theo-ry and clinical practice, and the theoretical innovation of TCM should be emphasized. There is no difference in the clinical value of drugs, and the key is to meet the clinical needs of patients. The research and development of new Chinese medicines ignores the theoretical guidance of Chinese medicine, and relying solely on animal experiment data may lead to failure of clinical trials. Different from the individualized treatment of TCM clinical syndrome differentiation, summarizing the core pathogenesis of TCM is the basis for the development of new Chinese medicines. It is necessary to summarize the pathogenesis of the disease under the guidance of TCM theory and encourage the application of modern medical methods to clarify the diagnosis of the disease. In view of the characteristics of new Chinese medicine research and development, it is proposed that the supporting role of human experience should be emphasized, and the technical points of clinical trials of new syndrome-type Chinese medicines should be explained.The use of objective indicators for syndrome evaluation, the selection of appropriate scales, and the formulation of reasonable treatment courses are advocated. During the research and development of new Chinese medicines, it is not only necessary to pay attention to modern medical safety indicators, but also to observe the evolution of TCM syndromes and specific TCM symptoms.

The relevant laws and regulations of drug clinical trials were introduced in this paper. It is pointed out that with drug re-gulatory laws and technological advances, clinical trials have become an important link in the development of new drugs of traditional Chinese medicines(TCM). Clinical trials of new drugs of TCM must comply with the requirement ofquot;Good Clinical Practice for Trial on Medicinal Productsquot;. In view of the particularities of clinical trials of new drugs of TCM, China has established an ethical review system for clinical research in TCM and carried out ethical review and certification of TCM research. In order to guide the development of clinical trials of new drugs of TCM, relevant departments have promulgated a series of guidelines for clinical trials of it, and established a new review system and technical requirements for clinical trials. Since 1983, thequot;national clinical pharmacology basequot; has been established. At present, there are 96 drug clinical trial institutions and 32 phase I clinical research wards in TCM hospitals, which can meet the development of clinical trials of new drugs of TCM. In the long-term practice, the technical team has continued to grow and develop, the research experience and technical strength have been significantly improved, and a large number of experts have become the backbone of clinical research in Chinese medicine. It is pointed out that we should attach importance to risk and benefit assessment, human experience, select scientific, objective and appropriate effectiveness indexes, evaluate the efficacy of TCM syndromes, and encourage the use of electronic methods in clinical research of new drugs of TCM. Based on the analysis of clinical trials of TCM in recent five years, it is pointed out that the active degree of clinical trials of new drugs of TCM is not high, the innovation ability of it is insufficient and the ability and enthusiasm of all aspects need to be improved. It is of great significance to carry out clinical trials of new traditional Chinese medicines to upgrade the TCM industry and produce high-level evidence-based medicine evidences. The high quality development of TCM can be promoted by strengthening clinical trials of new drugs of TCM.

A novel tungsten-doped CeO

The aims of this article were to determine the levels of serum high-sensitivity cardiac troponin T (hs-cTnT) in obstructive sleep apnea (OSA) patients without cardiovascular disease (CVD) and to assess the efficacy of continuous positive airway pressure (CPAP). Snorers referred for polysomnography (PSG) for the investigation of OSA were eligible and hs-cTnT levels measured in our pilot study. Hs-cTnT was measured again after 3 months of CPAP treatment in participants with severe OSA. A total of 93 participants recruited after PSG. When compared with simple snoring group, severe OSA group had comparable higher hs-cTnT (7.5 ± 3.0 vs. 5.0 ± 2.1; p < 0.05). Hs-cTnT was positively correlated with apnea hypopnea index, and oxygen desaturation index ( r = 0.283, 0.282; p = 0.006, 0.006, respectively). Hs-cTnT levels were not significantly altered in 28 individuals who received 3 months of CPAP treatment (8.4 ± 2.4 vs.7.6 ± 2.1; p = 0.064). Elevated hs-cTnT levels were observed in severe OSA patients without CVD, and CPAP treatment had no influence on this levels.

© 2001-2012 IEEE. Miniaturized electromagnetic sensors are increasingly introduced to navigate surgical instruments to anatomical targets during minimally invasive procedures, such as endoscopic surgery. These sensors are usually attached at the distal tips of surgical instruments to track their three-dimensional motion represented by the position and orientation in six degrees of freedom. Unfortunately, these sensors suffer from inaccurate measurements and jitter errors due to the patient movement (e.g., respiratory motion) and magnetic field distortion. This paper proposes an evolutionary computing strategy to optimize the sensor measurements and improve the tracking accuracy of surgical navigation. We modified two evolutionary computation algorithms and proposed adaptive particle swarm optimization (APSO) and observation-boosted differential evolution (OBDE) to enhance the navigation accuracy. The experimental results demonstrate that our modified algorithms to evolutionarily optimize electromagnetic sensor measurements can critically reduce the tracking error from 4.8 to 2.9 mm. In particular, OBDE outperforms APSO for electromagnetic endoscopic navigation.

Published articles regarding the blood levels of vascular endothelial growth factor (VEGF) in obstructive sleep apnea (OSA) patients are contradictory. The objective of this study was to explore whether VEGF levels is high or not in OSA subjects via quantitatively statistical analysis. The electronic databases of Pubmed, Web of Science, EMBASE were systematic searched. The VEGF levels and clinical characteristics of participants between OSA group and control group were extracted for analysis. Weighted mean difference (WMD) or standard mean difference (SMD) with 95 % confidence interval (CI) was calculated by fixed effects or random effects model. Appropriate statistical software was employed for data synthesis. Totaling 15 articles with 697 participants were included in this study. Pooled meta-analysis showed that blood VEGF concentrations were significantly higher in OSA patients than in control subjects (SMD 1.89, 95 % CI 0.92-2.87, p = 0.000). Subgroup analysis demonstrated that when compared with control group, OSA patients with age ≥50 years (SMD 2.54, 95 % CI 1.28-3.80, p = 0.000), apnea hypopnea index ≥30 events/h (SMD 2.47, 95 % CI 1.20-3.73, p = 0.000) had higher VEGF levels. Compared with control subjects, OSA patients had an elevated VEGF in serum (SMD 3.55, 95 % CI 1.82-5.28, p = 0.000) rather than in plasma. High blood VEGF concentrations were observed in OSA patients, particularly in the older and more serious patients.

Background. Microaspiration of secretions around the tracheal cuff is a multifactorial process. Tracheal cuff shape might take a major part in its occurrence. The rationale for producing a taper-shaped cuff is established on the assumption that compared to a conventional cuff with a single fixed diameter, a continuum of minimum-to-maximum diameter sections might better fit the tracheal walls. Objectives. The primary objective of this meta-analysis was to compare ventilator-associated pneumonia (VAP) between tapered-cuff intubation and conventional-cuff intubation. The secondary objective was to compare intensive care unit (ICU) mortality between tapered-cuff intubation and conventional-cuff intubation. Methods. We searched the Cochrane Library, Embase, MEDLINE database through the PubMed search engine, and CINAHL from inception to April 2018. Randomized trials comparing VAP and ICU mortality between tapered-cuff intubation and conventional-cuff intubation in intubated adults were included. Two review authors assessed study quality and abstracted databasing on prespecified criteria independently. Results. We pooled summary estimates from 5 trials evaluating tapered-cuff involving 774 participants. Compared to VAP, no statistically significant difference was observed between the tapered-cuff and conventional-cuff groups (OR 0.82, CI 0.61–1.12, z = 1.24, and p=0.21). No statistically significant difference was observed between the tapered-cuff and conventional-cuff groups with ICU mortality (OR 0.77, CI 0.55–1.08, z = 1.49, and p=0.14). Conclusions. In this meta-analysis, the tapered-cuff tracheal tube may not be superior to the standard-cuff tracheal tube in reducing VAP and ICU mortality.

This paper aims to solve the problem that the bookstore reader’s behavior can not automatically collect, by using IoT technology, provide a smart acquisition of the readers’ behavior system to bookstore. In this paper, through RFID, sensor, ZigBee and other technologies are used in the bookstore reader behavior acquisition system hardware and software design. The systems can intelligent collection which book are read and the length of each book browsing. This article mainly uses the IoT technology to achieve the bookstore reader behavior data stable collection, provides a data base for the reader behavior data analysis.

Positive airway pressure (PAP) has been recognized as an effective therapeutic option for sleep-disordered breathing (SDB) in patients with heart failure (HF), and it can improve left ventricular function. Whether PAP can ameliorate serum brain natriuretic peptide (BNP) levels, a biomarker of HF, is controversial. The purpose of the present study was to quantitatively assess the efficacy of PAP on BNP in patients with HF and SDB.A systematic search of PubMed, Embase, Web of Science and Cochrane library identified six randomized controlled trials (RCTs), in which PAP was compared with medical therapy, subtherapeutic PAP or different types of PAP. The data of BNP were extracted and pooled into meta-analysis using STATA 12.0.Totally 6 RCT studies (7 cohorts) with 222 patients were enrolled into analysis. The quality of each study was high and the heterogeneity (I(2) = 58.1%) was noted between studies. A significant reduction of BNP was observed after PAP treatment in patients with HF and SDB (SMD -0.517, 95% CI -0.764 to -0.270, z = 4.11, p = 0.000).Our meta-analysis of RCTs demonstrated that PAP elicits significant reduction of BNP in patients with HF and SDB.

Human vision system possesses a strong ability to interpret complex scenes in real time effortlessly and efficiently. However, computational modeling of basic intelligent behavior still remains a significant challenge in the fields of computer vision system. Different from context-aware saliency algorithm, our method for saliency detection, not only using basic properties of visual attention but also introducing local patches contrast cues, thus it can effectively improve the accuracy of visual saliency detection with relatively low computational complexity. Furthermore, the experimental results also indicate that the effectiveness of our proposed method.

With the application of the network technology in publishing, the publishing logistics has entered a new phase of globalization, networking, digital. Because there is no uniform standard information in the format code, copyright protection, etc ,it leads to the difficulties in information exchange, information sharing, etc. in the field of digital publishing logistics. In this paper, based on the current results of the digitized standard, it proposes the basis factors of the digital publishing logistics standards . The data - the degree of important of the factors influencing the development of standardization-can be got by using fuzzy hierarchy comprehensive evaluation to evaluate the factors. Under the guidance of the data, the most important standard can be determined to build in the process of the digital publishing logistics which are the basis data theories.

As the installed base of all other assemblies, the corn combine harvester chassis supports a variety of loads from the harvester and ground, so its reliability directly affects the quality and safety of the corn combine harvester. The analysis of corn combine harvester chassis was carried out with finite element analysis software. First, the 3D part of the chassis was established and simplified in accordance with the relevant principles. Second, the stress distribution and displacement of the chassis in the no-loaded and full-loaded conditions were calculated by meshing,applying loads and constraining boundary conditions. The analysis result is of great significance to enhance the quality and reliability of the chassis.

In view of the common oriented logistics robot is difficult to adapt to the complex and changeable requirements of modern logistics environment, a highly mobile logistics robot is developed based on the omni-directional mobile mechanism. In the course of the study, the mechanical body of omni-directional mobile logistics robot is designed by the three Swedish wheels structure, then the forward and inverse kinematic is analyzed s, and the result is simulated numerically for validating, finally a set of physical prototype is developed. The development of logistics robot with omni-directional mobile capability can improve the flexibility of logistics transmission equipment, increase the operational efficiency of logistics system and intelligent degree. It has a certain value for the related research for the application field of the robot and logistics equipment field.

On the background of railway freight transportation under emergency situations, the optimal evacuation function to minimize the total evacuation time and evacuation distance is put forward; in consideration of the dynamic and complex natures of evacuation network, searching evacuation route algorithm based on MMAS (Max-min ant colony algorithm) was proposed which can meet the dynamic change of evacuation network.

Use the standard 750ml bottle of red wine packaging design to explore the honeycomb core module of digital design and green manufacturing approach to virtual design and virtual manufacturing of new structural approach to packaging product development, through the final product form of reverse thrust reversers honeycomb core module data and processing forms, and finally the use of CNC machining centers cellular module manufacture.

This paper presents methods of cushioning package design. The analysis of existing shortcoming is made when the maximum accelerationstatic stress curve (what is called curve) is applied to the cushion package design, at the same time ,the principle and method steps to get curve are briefly introduced when the stressenergy method is used .the function between the key parameters of cushioning package design is acquired by the stressenergy method .By comparing the data produced with matlab software with the real experimental ones in some paper, the possibilities to get curve of casual drop height and cushion thickness by one-time experiment to get curve with stress-energy method is demonstrated. Based on the function of key parameters of cushioning package acquired, the reversed cushioning package design method is carried out.

Elevated levels of amyloid-β (Aβ) peptides, the main component of amyloid plaques in Alzheimer's disease, are the result of excessive β- and γ-cleavage of the amyloid precursor protein (APP) and/or impaired Aβ clearance in the brain. It has been suggested that high concentrations of luteinizing hormone (LH) in women contribute to increased Aβ generation after menopause, but the mechanism for this is incompletely understood. We investigated the effect of human chorionic gonadotropin (hCG), an LH receptor agonist, on APP β-cleavage in the SH-SY5Y neuroblastoma cell line. Treatment of these cells with hCG-induced elevated β-cleavage in a dose-dependent manner: administration of 30 mIU but not 10 mIU/ml of hCG significantly increased sAPPβ levels in the cell medium 1.7-fold as measured by ELISA. These results support the notion that LH contributes to elevated Aβ levels at least in part by increasing β-cleavage of APP by β-site APP cleaving enzyme. NHMRC grant: 1045964

Based on the background of cushioning package design for the wine bottles, the analysis on the cushioning properties of honeycomb paper core is presented. The reverse design method based on the function relationship of cushioning package is proposed, to make the cushioning structure design and cushioning dimension design as well as the buffering pad checkout, including strength check, deflection check and creep deformation check to make sure design meets the requirements. The function relation of the maximum acceleration and static stress between arbitrary dropping height and thickness of cushion is obtained. The reverse design method can obtain any curve of any dropping height and any cushioning thickness through several experimental tests. The flexibility, what is more important is that the method can greatly reduce test time, saves the cost of enterprises and technology research & development. The method provides a new way to the cushioning package design.

Based on the analysis of the loads, constraints and its mechanisms applying to the duct system, a finite element model of the anti-ice system is developed and the Lanczos algorithm is used for modal analysis. Then, the first eight natural frequencies and vibration modes are obtained. The thermodynamic parameters of the gas and the kinetic parameters of the ball joint which have influence on the modal analysis are considered. The results show that the first eight order natural frequencies of the anti-ice Part1 are low and concentrated, and decrease with temperature of the gas while increase with pressure of the gas. Meanwhile, the natural frequencies increase with the stiffness and starting torque of the ball joint. This work could be helpful for reliability design of civil-aircraft ducting system.

The force analysis on the in-plane and out-of-plane of honeycomb core referring to some related articles is presented. during the transportation of wine, the honeycomb paper core is under three-dimensional stress. According to stress condition in the process of wine packaging and transportation, based on the fourth strength principle, the equivalent load is obtained. And the stress with different stretching angels with virtual sampling method is calculated. Thus, the optimal stretching angle of honeycomb paper is acquired, which is .

The development of urban rail transit plays the more and more important role in the public transit. It’s significant to analyze the urban rail transit network characteristics and its stability. The basic statistics parameters of Beijing metro network are computed in the paper based on the theory of complex networks, and its network characteristic is analyzed through the comparison to characteristic parameters of four typical networks.

Background:The influence of the subglottic secretion drainage (SSD) on the microorganisms of ventilator associated pneumonia (VAP) is still unclear.A meta-analysis focusing on the influence of the SSD on the microorganisms of VAP.Methods:A comprehensive search was conducted through the onlin

Betaine serves as a methyl donor in a reaction converting homocysteine to methionine. It is commonly used for the treatment of hyperhomocysteinemia in humans, which indicates it may be associated with reduced risk of atherosclerosis. However, there have been few data regarding its vascular effect.To investigate the effect of betaine supplementation on atherosclerotic lesion in apolipoprotein (apo) E-deficient mice.Four groups of apoE-deficient mice were fed AIN-93G diets supplemented with 0, 1, 2, or 4 g betaine/100 g diet (no, 1, 2, and 4% betaine, respectively). Wild-type C57BL/6 J mice were fed AIN-93G diet (wild-type). Mice were sacrificed after 0, 7, or 14 weeks of the experimental diets. Atherosclerotic lesion area in the aortic sinus, levels of tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 in aorta and serum, serum lipids, and methylation status of TNF-alpha promoter in aorta were determined.Linear regression analysis showed that the higher dose of betaine was related to smaller atherosclerotic lesion area (beta = -11.834, P0.001). Compared with no-betaine mice after 14 weeks, mice receiving 1%, 2%, or 4% betaine had 10.8, 41, and 37% smaller lesion area, respectively. Betaine supplementation also reduced aortic expression of TNF-alpha in a dose-dependent way in four groups of apoE-deficient mice, and Pearson correlation revealed that atherosclerotic lesion area was positively associated with aortic TNF-alpha level (r = 0.777, P0.001). Although serum TNF-alpha levels were lower in betaine-supplemented mice than in no-betaine mice after fourteen weeks of treatment (P0.001), we did not observe a significant dosage effect (P = 0.11). However, methylation level of TNF-alpha promoter did not differ among groups at any time. In this study, apoE-deficient mice receiving betaine supplementation for 14 weeks had higher concentrations of serum total cholesterol (P0.01), LDL cholesterol (P0.05), and lower body weight (P0.05) than no-betaine mice.These data suggest that despite exacerbating hyperlipidemia in apoE-deficient mice, betaine may exert its anti-atherogenic effect by inhibiting aortic inflammatory response mediated by TNF-alpha.

Based on turbulent theory, a 3D coupled model of fluid flow and solidification was built using finite difference method and used to study the influence of superheating degree and casting speed on fluid flow and solidification, analyze the interaction between shell and molten steel, and compare the temperature distribution under different technological conditions. The results indicate that high superheating degree can lengthen the liquid-core depth and make the crack and breakout possible, so suitable superheating should be controlled within 35 °C according to the simulation results. Casting speed which is one of the most important technological parameters of improving production rate, should be controlled between 0.85 m/min and 1.05 m/min and the caster has great potential in the improvement of blank quality.

A 3-D coupled numerical model for flowing distribution and temperature distribution in twins strip roll-casting process is developed, and the influence of technological parameter on roll-casting process is studied. As a result, lower superheat can get more homogeneity structure in thickness direction, but the metal will solidify in the casting system if the superheat is too low, which doesn’t benefit the slag inclusion floating up. When the velocity is between 6m/mim and 8m/min, the end-point will be at 2~8mm above the anastomotic point. The model can provide the theory to the control on strip roll-casting process.

Phosphorylation of residues in the C-terminal tail of the µ-opioid receptor (MOPr) is thought to be a key step in desensitization and internalization. Phosphorylation of C-terminal S/T residues is required for internalization (Just et al., 2013), but its role in desensitization is unknown. This study examined the influence of C-terminal phosphorylation sites on rapid desensitization of MOPr. Wild-type MOPr, a 3S/T-A mutant (S363A, T370A, S375A) that maintains internalization, 6S/T-A (S363A, T370A, S375A, T376A, T379A, T383A) and 11S/T-A (all C-terminal S/T residues mutated) mutants not internalized by MOPr agonists were stably expressed in AtT20 cells. Perforated patch-clamp recordings of MOPr-mediated activation of G-protein-activated inwardly rectifying potassium channel (Kir3.X) (GIRK) conductance by submaximal concentrations of Met(5)-enkephalin (ME) and somatostatin (SST; coupling to native SST receptor [SSTR]) were used to examine desensitization induced by exposure to ME and morphine for 5 minutes at 37°C. The rates of ME- and morphine-induced desensitization did not correlate with phosphorylation using phosphorylation site-specific antibodies. ME-induced MOPr desensitization and resensitization did not differ from wild-type for 3S/T-A and 6S/T-A but was abolished in 11S/T-A. Morphine-induced desensitization was unaffected in all three mutants, as was heterologous desensitization of SSTR. Morphine-induced desensitization (but not ME) was reduced by protein kinase C inhibition in wild-type MOPr and abolished in the 11S/T-A mutant, as was heterologous desensitization. These findings establish that MOPr desensitization can occur independently of S/T phosphorylation and internalization; however, C-terminal phosphorylation is necessary for some forms of desensitization because mutation of all C-terminal sites (11S/T-A) abolishes desensitization induced by ME.

Background Peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1A/ PGC-1α) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. The activity of PGC-1α or genetic variations in the gene encoding the enzyme may contribute to individual variations in mitochondrial function and insulin resistance or diabetes. The objective of this study was to assess the extent to which PPARGC1A (rs8192678) and serum uric acid (UA) and its interaction impact on T2DM susceptibility in Chinese Han population. Method We conducted a study in a cohort that included 1166 T2DM patients and 1135 controls, and was genotyped for the presence of the PPARGC1A rs8192678 polymorphisms. Genotyping was performed by iPLEX technology. The association between rs8192678 or UA and T2DM was assessed by univariate and multivariate logistic regression (MLR) analysis controlling for confounders. The interaction between rs8192678 and UA for T2DM susceptibility was also assessed by MLR analysis. Results The generalized linear regression analysis failed to show an association between the PPARGC1A rs8192678 polymorphisms and T2DM. Interestingly, the present study provided data suggesting that the minor A-allele of PPARGC1A (rs8192678) had a protective effect against T2DM in subjects with higher level of UA (ORint =1.50 95% CI: 1.06-2.12 for allele and P = 0.02, ORint =1.63 95% CI: 1.17-2.26 for genotype and P = 0.004). Conclusion The combination of higher level of UA and PPARGC1A (rs8192678) was an independent predictor for T2DM.

Objective To evaluate the efficacy of continuous positive airway pressure (CPAP) on serum testosterone in men with obstructive sleep apnea (OSA). Methods Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before June 2014. Information on characteristics of subjects, study design, pre- and post-CPAP treatment of serum total testosterone, free testosterone and sexual hormone blinding protein (SHBG) was extracted for analysis. Results A total of 7 studies with 9 cohorts that included 232 men were pooled into meta-analysis. There was no change of total testosterone levels before and after CPAP treatment in OSA men (standardized mean difference (SMD) = -0.14, 95%CI: -0.63 to 0.34, z = 0.59, p = 0.558), even subdivided by CPAP therapeutic duration (>3 months). Meanwhile, no significant differences in free testosterone and SHBG were detected after CPAP treatment (SMD = 0.16, 95%CI: -0.09 to 0.40, z = 1.25, p = 0.211 and SMD = -0.58, 95%CI: -1.30 to 0.14, z = 1.59, p = 0.112, respectively). Conclusion CPAP has no influence on testosterone levels in men with OSA, further large-scale, well-design interventional investigation is needed.

Opioids are widely prescribed analgesics, but their use is limited due to development of tolerance and addiction, as well as high variability in individual response. The development of improved opioid analgesics requires high-throughput functional assays to assess large numbers of potential opioid ligands. In this study, we assessed the ability of a proprietary "no-wash" fluorescent membrane potential dye to act as a reporter of µ-opioid receptor (MOR) activation and desensitization via activation of G-protein-coupled inwardly rectifying potassium channels. AtT-20 cells stably expressing mouse MOR were assayed in 96-well plates using the Molecular Devices FLIPR membrane potential dye. Dye emission intensity decreased upon membrane hyperpolarization. Fluorescence decreased in a concentration-dependent manner upon application of a range of opioid ligands to the cells, with high-efficacy agonists producing a decrease of 35% to 40% in total fluorescence. The maximum effect of morphine faded in the continued presence of agonist, reflecting receptor desensitization. The effects of opioids were prevented by prior treatment with pertussis toxin and blocked by naloxone. We have demonstrated this assay to be an effective method for assessing ligand signaling at MOR, which may potentially be scaled up as an additional high-throughput screening technique for characterizing novel opioid ligands. NHMRC Grant Numbers: 1011979 & 1045964