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Background. T cell-mediated antitumor immune response is the basis of colorectal cancer (CRC) immunotherapy. Cholesterol plays an important role in T cell signal transduction and function. Apolipoprotein E (APOE) plays a major role in cholesterol metabolism. Objective. To screen and analyze key markers involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism. Methods. Based on the median cutoff of the expression value of APOE according to the data downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database, patients were grouped into low and high expression groups. Differences in clinical factors were assessed, and survival analysis was performed. Differentially expressed genes (DEGs) in the high and low expression groups were screened, followed by the analysis of differences in tumor-infiltrating immune cells and weighted gene coexpression network analysis results. The closely related genes to APOE were identified, followed by enrichment analysis, protein–protein interaction (PPI) network analysis, and differential expression analysis. Immunohistochemical staining (IHC) was used to detect the expression of CD8 in CRC tissues. Results. There were significant differences in prognosis and pathologic_N between the APOE low and high expression groups. A total of 2,349 DEGs between the high and low expression groups were selected. A total of 967 genes were obtained from the blue and brown modules. The probability of distribution of CD8+ T cells differed significantly between the two groups, and 320 closely related DEGs of APOE were screened. Genes including the HLA gene family, B2M, IRF4, and STAT5A had a higher degree in the PPI network. GEO datasets verified the prognosis and the related DEGs of APOE. IHC staining verified the relationship between the distribution of CD8+ T cells and APOE expression. Conclusion. Genes including the HLA gene family, B2M, IRF4, and STAT5A might be the key genes involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism.

Metabolic syndrome (MetS) is characterized by a group of metabolic disturbances which leads to the enhanced risk of cancer development. Elucidating the mechanisms between these two pathologies is essential to identify the potential therapeutic molecular targets for colorectal cancer (CRC). 716 colorectal patients from the First and Second Affiliated Hospital of Wenzhou Medical University were involved in our study and metabolic disorders were proven to increase the risk of CRC. The prognostic value of the MetS factors was analyzed using the Cox regression model and a clinical MetS-based nomogram was established. Then by using multi-omics techniques, the distinct molecular mechanism of MetS genes in CRC was firstly systematically characterized. Strikingly, MetS genes were found to be highly correlated with the effectiveness of targeted chemotherapy administration, especially for mTOR and VEGFR pathways. Our results further demonstrated that overexpression of MetS core gene IL6 would promote the malignancy of CRC, which was highly dependent on mTOR-S6K signaling. In conclusion, we comprehensively explored the clinical value and molecular mechanism of MetS in the progression of CRC, which may serve as a candidate option for cancer management and therapy in the future.

Gastric cancer (GC) is a typical heterogeneous malignant tumor, whose insensitivity to chemotherapy is a common cause of tumor recurrence and metastasis. There is no doubt regarding the effectiveness of adjuvant chemotherapy (ACT) for GC, but the population for whom it is indicated and the selection of specific options remain the focus of present research. The conventional pathological TNM prediction focuses on cancer cells to predict prognosis, while they do not provide sufficient prediction. Enhanced computed tomography (CT) scanning is a validated tool that assesses the involvement of careful identification of the tumor, lymph node involvement, and metastatic spread. Using the radiomics approach, we selected the least absolute shrinkage and selection operator (LASSO) Cox regression model to build a radiomics signature for predicting the overall survival (OS) and disease-free survival (DFS) of patients with complete postoperative gastric cancer and further identifying candidate benefits from ACT. The radiomics trait-associated genes captured clinically relevant molecular pathways and potential chemotherapeutic drug metabolism mechanisms. Our results of precise surrogates using radiogenomics can lead to additional benefit from adjuvant chemotherapy and then survival prediction in postoperative GC patients.

A planar reflectarray antenna based on liquid crystal materials is presented in this paper. First, a new type of loop dipole miniaturized liquid crystal antenna reflection unit is constructed. The reflector unit can achieve 400° phase shift at 35GHz, and the loss is less than 4.5dB. Then, an 11×11 liquid crystal reflectarray antenna is designed using this unit, and the main beam scanning angle range of the array antenna reached ±20°. When the deflection angle of the array antenna is 20°, the gain of the antenna is 14.9dBi, and the first sidelobe level is −9.1dB.

This paper designs a miniaturized reflective phase shifter based on liquid crystal. The phase shifter adjusts the dielectric constant of the liquid crystal to cause the load impedance to change, thereby realizing the phase change at the output of the coupler. Through the multilayer circuit structure, the miniaturization of the phase shifter is realized. In the operating bandwidth of 14GHz∼16GHz, the return loss is better than −10.89dB, the insertion loss is better than 5.7dB, and the maximum phase shift exceeds 320°.

Medication nonadherence is associated with an increased risk of complications in hypertensive patients. We investigated behavioral factors associated with medication nonadherence in hypertensive patients in southern Taiwan. Using questionnaires, we collected data regarding clinicodemographic characteristics and nonadherence behaviors from 238 hypertensive patients. We assessed the self-reported prevalence of specific behaviors of medication nonadherence and investigated factors associated with each behavior using multivariable logistic regression analysis. The most common behavior of medication nonadherence was forgetting to take medication (28.6%), followed by discontinuing medication (9.2%) and reducing the medication dose (8.8%). Age ≥ 65 years (adjusted odds ratio [aOR] = 0.32, 95% confidence interval [CI] = 0.15–0.69) and male sex (aOR = 2.61, CI = 1.31–5.19) were associated with forgetting to take medication. The presence of comorbidities (diabetes, kidney disease, or both) and insomnia (aOR = 3.97, 95% CI = 1.30–12.1) was associated with reducing the medication dose. The use of diet supplements was associated with discontinuing the medication (aOR = 4.82, 95% CI = 1.50–15.5). Compliance with a low oil/sugar/sodium diet was a protective factor against discontinuing medication (aOR = 0.14, 95% CI = 0.03–0.75). The most pervasive behavior associated with medication nonadherence among hypertensive patients was forgetting to take medication. Age &lt, 65 years, male sex, comorbidities, insomnia, noncompliance with diet, and the use of dietary supplements were specifically associated with medication nonadherence.

BackgroundThe therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy.Material and MethodsWe consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI–treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed.ResultsIn total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, PEGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS.ConclusionsEGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs.

The grand challenge to meet the increasing demands for food by a rapidly growing global population requires protecting crops from pests. Natural active substances play a significant role in the sustainable pests and pathogenic microbes management. In recent years, natural products- (NPs), antimicrobial peptides- (AMPs), medicinal plant- and plant essential oils (EOs)-related online resources have greatly facilitated the development of pests and pathogenic microbes control agents in an efficient and economical manner. However, a comprehensive comparison, analysis and summary of these existing web resources are still lacking. Here, we surveyed these databases of NPs, AMPs, medicinal plants and plant EOs with insecticidal, antibacterial, antiviral and antifungal activity, and we compared their functionality, data volume, data sources and applicability. We comprehensively discussed the limitation of these web resources. This study provides a toolbox for bench scientists working in the pesticide, botany, biomedical and pharmaceutical engineering fields. The aim of the review is to hope that these web resources will facilitate the discovery and development of potential active ingredients of pests and pathogenic microbes control agents.

Relying on the Biomedical Big Data Center of West China Hospital, this paper makes an in-depth research on the construction method and application of breast cancer-specific database system based on full data lifecycle, including the establishment of data standards, data fusion and governance, multi-modal knowledge graph, data security sharing and value application of breast cancer-specific database. The research was developed by establishing the breast cancer master data and metadata standards, then collecting, mapping and governing the structured and unstructured clinical data, and parsing and processing the electronic medical records with NLP natural language processing method or other applicable methods, as well as constructing the breast cancer-specific database system to support the application of data in clinical practices, scientific research, and teaching in hospitals, giving full play to the value of medical big data of the Biomedical Big Data Center of West China Hospital.

In a context of fragmentated competition and consumers’ demand, it is difficult to take advantage of the low cost and high efficiency of mass customization, while and also meeting the customers’ individualized needs. Internet led business increases the difficulty of balancing the offer of large production and customization, because companies face a high cost (C2F), while the customer’s satisfaction is low (F2C). Finding a solution to this trade-off is not only a major challenge in the process of company model transformation, but also an important topic that has not yet been studied in depth. This research applied the case analysis method to study the evolution of hotel furniture company innovation ecosystem and to suggest the development of value cocreation model. Meanwhile, the C2F2C development strategy of creating value between hotel furniture manufacturers and customers is constructed, which realizes the win-win value creation between companies and customers, and explores the effective ways to improve the technological innovation ability and international competitiveness of hotel furniture manufacturers in China.

Objective The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor-infiltrating immune cells activated and recruited to the cancer microenvironment. However, a comprehensive introduction of gastric cancer immune cell infiltration has not been identified so far. Methods In this study, we comprehensively analyzed the tumor-infiltrating immune cells abundance in gastric cancer for the first time by CIBERSORT. The meta-analysis, single-sample gene set enrichment analysis and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. The fraction of tumor-infiltrating immune cells subpopulations was also evaluated to determine the associations with clinical features and molecular subtypes. Results Tumor-infiltrating immune cells are extensively involved in the pathogenesis and development of the gastric cancer. We discovered Tfh and activated CD4+ memory T cells were associated with poorer overall survival and Progression-free survival (PFS), but that naïve B cells were opposite for PFS. Unsupervised clustering analysis revealed there existed three tumor-infiltrating immune cells subgroups with distinct survival patterns. Specially, cluster 1 showed significantly better clinical outcome than other two clusters. Conclusions Collectively, our data explored the differences of tumor-infiltrating immune cells in gastric cancer, and these variations were likely to be important clues for prognosis and management of its future clinical implementation.

Broad absorption is a desired characteristic of materials employed in the photoactive layers of organic photovoltaic (OPV) devices. Here, we have identified tetrabenzotriazacorroles (Tbcs) as complementary absorbing chromophores and electron donors to the promising nonfullerene acceptors boron subphthalocyanines (BsubPcs). These two materials, which can be utilized as donor–acceptor pairs within fullerene-free OPVs, yield spectral coverage over the entire visible range of 300–750 nm. Oxy phosphorus Tbc derivative (POTbc) was employed as an electron donor and paired initially with multiple BsubPc derivatives having a distribution of highest occupied molecular orbital/lowest unoccupied molecular orbital energy levels in planar heterojunction OPVs. These devices were “gray/black” due to the broad absorption across the visible spectrum. Upon screening, the partially halogenated chloro hexachloro BsubPc (Cl–Cl6BsubPc) showed the greatest promise for coupling with POTbc. The thickness ratio and total thickness of the active layer were then probed in order to identify the optical and electrical limitations on the POTbc/Cl–Cl6BsubPc-based OPV device. A maximum power conversion efficiency (PCE) of 2.13% was achieved at 60 nm total thickness of the active layer and 1 to 3 (POTbc to Cl–Cl6BsubPc) thickness ratio. Outdoor stability of the champion device was evaluated using protocols established by International Summits on OPV Stability and was found to be on par with an α-sexithiophene/Cl–Cl6BsubPc baseline OPV.

Objective To explore training-related independent factors affecting the awareness of cardiopulmonary resuscitation (CPR) in senior high school students in Shanghai. Methods Questionnaires measuring CPR-related knowledge were distributed to 430 senior high school students in Shanghai. Results The overall CPR qualification rate was 7.7%. Qualification rate increased significantly with training frequency (5.5% vs. 9.3% vs. 20%), personal willingness to perform CPR (3.7% vs. 9.5%) and smaller training intervals (12.8% vs. 5.3% vs. 1.8%). After adjustment, training interval

PURPOSE: To validate the feasibility and efficacy of intratumoral radiofrequency hyperthermia (RFH)-enhanced herpes simplex virus (HSV) thymidine kinase (TK) and ganciclovir (GCV) (hereafter, HSV-TK/GCV) gene therapy for non–small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This study was performed from November 11, 2015, to April 14, 2017, and included (a) in vitro experiments with human NSCLC cells to establish the proof of principle, (b) in vivo experiments using mice with subcutaneous NSCLC to further demonstrate the principle, and (c) in vivo experiments using rats with orthotopic NSCLC to validate the technical feasibility. Cells, nude mice, and nude rats were randomly divided into four groups (six animals per group): (a) combination therapy (HSV-TK/GCV combined with RFH), (b) RFH, (c) HSV-TK/GCV, and (d) phosphate-buffered saline. Data were analyzed by using the Dunnett t test or Kruskal–Wallis test. RESULTS: For in vitro experiments, the cell proliferation assay showed significantly diminished viable cells with combination therapy (mean, 0.56; 95% confidence interval [CI]: 0.44, 0.68) versus RFH (mean, 0.89; 95% CI: 0.82, 0.97), HSV-TK/GCV (mean, 0.71; 95% CI: 0.56, 0.86), and phosphate-buffered saline (mean, 1; 95% CI: 1, 1) (P < .05 for all). For in vivo experiments, optical imaging showed significantly decreased relative bioluminescence signal with combination therapy (mean, 0.71 [95% CI: 0.03, 1.39] in mice; 1.29 [95% CI: 0.51, 2.06] in rats) compared with RFH (mean, 2.66 [95% CI: 1.73, 3.59] in mice; 2.26 [95% CI: 1.51, 3.01] in rats), HSV-TK/GCV (mean, 1.37 [95% CI: 0.65, 2.08] in mice; 1.76 [95% CI: 1.20, 2.31] in rats), and phosphate-buffered saline (mean, 3.07 [95% CI: 2.50, 3.65] in mice; 2.94 [95% CI: 2.29, 3.58] in rats) (P < .001 for all). US showed that the smallest relative tumor volumes occurred with combination therapy (mean, 0.60; 95% CI: 0.15, 1.05) versus RFH (mean, 2.43; 95% CI: 1.80, 3.06), HSV-TK/GCV (mean, 1.32; 95% CI: 0.75, 1.89), and phosphate-buffered saline (mean, 2.56; 95% CI: 1.75, 3.38) (P < .05 for all) in the mouse subcutaneous model. CONCLUSION: Intratumoral radiofrequency hyperthermia–enhanced herpes simplex virus thymidine kinase and ganciclovir gene therapy for non–small-cell lung cancer is feasible and can be guided by molecular imaging. © RSNA, 2018

// Fu Xiong 1, 2, * , Feng Zhang 2, * , Yin Jin 2 , Qiaoyou Weng 2 , Jingjing Song 2 , Guofeng Zhou 1 , David Shin 2 , Chuansheng Zheng 1 and Xiaoming Yang 2 1 Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430022, China 2 Image-Guided Bio-Molecular Intervention Research and Section of Vascular & Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA 98109, USA * These authors have contributed equally to this work Correspondence to: Xiaoming Yang, email: xmyang@uw.edu Chuansheng Zheng, email: hqzcsxh@sina.com Keywords: radiofrequency hyperthermia; gene therapy; hepatocellular carcinoma; molecular imaging Received: July 04, 2017 Accepted: September 08, 2017 Epub: December 22, 2017 Published: March 06, 2018 ABSTRACT Purpose: To validate the feasibility of using interventional radiofrequency hyperthermia(RFH) to enhance herpes simplex virus-thymidine kinase (HSV-TK)/ganciclovir (GCV) gene therapy of rat orthotopic hepatic cancer. Material and Methods : Rat hepatocellular carcinoma cells (MCA-RH-7777) were transduced with lentivirus/luciferase gene for optical imaging. In-vitro experiments with the luciferase cells and in-vivo experiments on rats with orthotopic hepatic tumors were divided into four treatment groups: (i) HSV-TK/GCV-mediated gene therapy combined with RFH; (ii) gene therapy alone; (iii) RFH alone; and (iv) phosphate buffered saline (PBS). Cell viability was evaluated by MTS assay and confocal microscopy, and HSV-TK gene expression in cells and tumors was quantified by western blotting. Bioluminescent optical imaging and ultrasound imaging were used to monitor and compare the photon signal and tumor size changes among different treatment groups overtime, respectively. The imaging findings were correlated with histology. Results: For in-vitro experiments, the combination therapy group (gene therapy + RFH) demonstrated the lowest cell proliferation by MTS assay, compared to the gene therapy alone, RFH alone, and PBS (26.1±3.2% vs 50.4±4.6% vs 82.9±6.3% vs 100%, p

This paper analyzed the competitiveness of premium and regular Fair Trade and Organic (FTO) coffees relative to conventional coffee using consumer panel data. The coffees were categorized into four groups based on their certification labels and prices: Premium or Regular Conventional, and Premium or Regular FTO. Competitiveness was measured in terms of price sensitivity and substitution behavior in the entire market and in segments of core consumers who spent most of their coffee budgets on FTO coffees. We found that most consumers were more likely to substitute both FTO products for conventional products, and less likely to substitute out of conventional products. Even the core consumers of Premium FTO coffees, who had inelastic demand for that type of coffee, were more likely to switch to Regular Conventional coffees than to Regular FTO coffees, even though both alternatives were similarly low-priced. The results suggest that even core FTO market segments were not strongly committed to certified products. Companies making and selling certified products need to do more beyond matching prices and using sustainability certification labels to increase their market competitiveness and potential options are discussed in this paper.

// Qin-Fen Chen 1, * , Xiao-Dong Zhou 2, * , Dan-Hong Fang 3 , Yang-Jie Sun 1 , Qian Zhao 1 , Jun-Hua Huang 1 , Yin Jin 1 and Jian-Sheng Wu 3 1 Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China 2 Department of Cardiovascular Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China 3 Medical and Health Care Center, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China * Co-first author Correspondence to: Jian-Sheng Wu, email: wenzhouwujs@163.com , wzwujs@wzhospital.cn Keywords: colorectal polyps, smoking, non-alcoholic fatty liver disease, health check Received: February 27, 2017 Accepted: July 25, 2017 Published: August 24, 2017 ABSTRACT Objectives: Non-alcoholic fatty liver disease (NAFLD) and smoking have similar mechanisms of promoting colorectal polyps. The potential link between NAFLD and smoking in men and colorectal polyps has not been adequately evaluated. The aim is to investigate this association. Methods: A retrospective cross-sectional study was conducted on 2409 individuals undergoing a health check. Univariate and multivariate logistic regression were performed for analyzing the association between risk factors and colorectal polyps. Individuals were divided into four groups: Q1: NAFLD (-)/smoking (-); Q2: NAFLD (+)/smoking (-); Q3: NAFLD (-)/smoking (+); Q4: NAFLD (+)/smoking (+). Logistic analyses were used to explore associations for the whole study population and stratified groups. Results: The prevalence of colorectal polyps was 38.8% in males, and that of colorectal polyps in smokers and individuals with NAFLD were 47.0% (428/911) and 42.9% (267/622), respectively. With Q1 as reference, subjects with NAFLD (+) and smoking habits (+) had the highest ORs for colorectal polyps (OR = 2.64, 95% CI: 1.91 - 3.64, P < 0.001), adenomatous polyps (OR = 2.06, 95% CI: 1.38 - 3.05, P < 0.05), non-adenomatous polyps (OR = 1.97, 95% CI: 1.39 - 2.80, P < 0.05), ≥ 3 polyps (OR = 2.05, 95% CI: 1.31 - 3.22, P < 0.05) and proximal polyps (OR = 1.58, 95% CI: 1.02 - 2.45, P < 0.05) after adjusting for confounding variables. Conclusions: Men with NAFLD and smoking habits have an increasing risk of colorectal polyps.

AIM To investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and colorectal adenomatous and hyperplastic polyps. METHODS A retrospective cross-sectional study was conducted on 3686 individuals undergoing health checkups (2430 males and 1256 females). All subjects underwent laboratory testing, abdominal ultrasonography, colonoscopy, and an interview to ascertain the baseline characteristics and general state of health. Multinomial logistic regression analysis was performed to examine the association between NAFLD and the prevalence of colorectal adenomatous and hyperplastic polyps. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on number, size, and location of colorectal polyps. RESULTS The prevalence of colorectal polyps was 38.8% in males (16.2% for adenomatous polyps and 9.8% for hyperplastic polyps) and 19.3% in females (8.4% for adenomatous polyps and 3.9% for hyperplastic polyps). When adjusting for confounding variables, NAFLD was significantly associated with the prevalence of adenomatous polyps (OR = 1.28, 95%CI: 1.05-1.51, P < 0.05) and hyperplastic polyps (OR = 1.35, 95%CI: 1.01-1.82, P < 0.05). However, upon analyzing adenomatous and hyperplastic polyps in different sex groups, the significant association remained in males (OR = 1.53, 95%CI: 1.18-2.00, P < 0.05; OR = 1.42, 95%CI: 1.04-1.95, P < 0.05) but not in females (OR = 0.44, 95%CI: 0.18-1.04, P > 0.05; OR = 1.18, 95%CI: 0.50-2.78, P > 0.05). CONCLUSION NAFLD is specifically associated with an increased risk of colorectal adenomatous and hyperplastic polyps in men. However, NAFLD may not be a significant factor in the prevalence of colorectal polyps in women.

Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1β, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis.

Aim To identify the factors affecting the pharmacokinetics (PKs) of sirolimus in healthy Chinese subjects and renal transplant patients. Methods A population PK model of sirolimus was constructed using dense data from 22 healthy volunteers and sparse data from 105 renal transplant patients. Results The data were well described by a two-compartment model with first-order absorption. The estimates of absorption rate constant (Ka), clearance (CL/F), and central volume of distribution (V2/F) were 0.24 h(-1), 8.81 L/h, and 676 L, respectively. The CL/F in renal transplant patients was 45.5% lower than that in healthy subjects. Based on the final model, CL/F decreased significantly with increasing cyclosporine (CsA) daily dose and age. A decrease of 7.3% in CL/F for every 100-mg increase in the CsA daily dose and a decrease of 34.2% in CL/F for every 20-year increase in age was observed. Moreover, V2/F increased significantly with increasing serum creatinine in our study. However, the range of serum creatinine concentration and the interindividual variability for V2/F are large. Conclusion This is the first study to characterize the population PKs of sirolimus using a two-compartment model in healthy Chinese subjects and renal transplant patients. A decrease of 7.3% in the sirolimus CL/F for every 100-mg increase in the CsA daily dose and a decrease of 34.2% in the sirolimus CL/F for every 20-year increase in age was observed, which allowed us to better optimize sirolimus dosing regimens in Chinese renal transplant patients.

Background Moyamoya disease or syndrome (MMD or MMS) is a cerebrovascular disease characterized by stenosis or occlusion of the distal portion of the internal carotid arteries, with ultimate spread to the proximal portion of the anterior cerebral arteries and middle cerebral arteries (MCAs). In the present study, we wanted to evaluate the usefulness of conventional computed tomography (CT) and axial magnetic resonance (MR) T2-weighted imaging (T2WI) for the examination of horizontal segments of the MCAs (ie, M1 segments) in patients diagnosed with MMD or MMS. Methods This study enrolled 29 patients (n = 11 men; n = 18 women), who underwent conventional CT and/or MR T2WI. CT angiography, MR angiography, or digital subtraction angiography was used as a reference. CT and MR imaging data were reviewed by 2 experienced radiologists, who analyzed and recorded stenosis or occlusions of the M1 segments. We performed statistical analyses to compare the diagnostic accuracy of both techniques on M1 segments in MMD or MMS. Results Fifty-three steno-occlusive changes of M1 segments were revealed by angiography in the 29 patients. T2W-MRI allowed the identification of moyamoya vessels with 100% success rate. Stenosis and occlusion of M1 segments were better visualized on axial T2W-MRI compared to conventional CT (94.59% versus 71.43%; P = .008). Conclusions Our study showed that conventional CT and axial T2W-MRI could be used to identify the steno-occlusive changes of the horizontal segment of the MCA in MMD or MMS, which may have a significant impact on the accurate diagnosis of this disease at its early stage.

To promote the standardization and assembly of temporary roads for construction, according to the investigation and research, combined with the requirements of the code, from the perspective of bearing capacity and economy, a standardized construction temporary road scheme was proposed. The load and temperature stresses of assembled panels of different sizes were analyzed using the elastic ground plate theory. The load stress is significantly affected by the axle load of vehicle, and the temperature stress is significantly affected by the plate length. Plate length should not exceed 4m. The numerical analysis method was adopted and the joints were optimized. The tenon could effectively transfer the load. While the length of the tenon is 4cm, the load transfer effect is the best.

Waste CRTs display funnel glass contains a lot of lead, and improper disposalof waste CRTs funnel glass is easy to cause greater environmental risks. Three extraction systems of citric acid/sodium citrate, EDTA-2Na, and citric acid/sodium citrate/EDTA-2Na were used to leach the lead in waste CRTsfunnel glass. The effect of extraction rate for three extraction systems was investigated. The results showed that the effect of the extraction systems of citric acid/sodium citrate/EDTA-2Na to leaching the lead in waste CRTs could reach more than 80%, which provides a way for the green treatment of waste CRTs.

We have developed one versatile spatially confined self-assembly strategy to integrate cyanometallate-based coordination polymers with functional metal oxides into well-defined core@shell heterostructures. The structure, composition, size and morphology of the heterostructures could be facilely controlled. The obtained Fe3O4@Prussian blue heterostructure was evaluated as an appealing multifunctional thermal ablation agent exhibiting response to both magnetic field and light irradiation.

In a photovoltaic system, function of islanding detection is an essential part of inverter. The system should not only fast detect islanding, but also minimize the impact on power grid. The relationship between the output current THD and the time of detection is discussed. This problem is analyzed in this paper and a new algorithm is proposed. Based on the improved AFDPF algorithm, this method effectively regulate the relationships between the truncated coefficient (cf), current harmonic distortion and island detection time and on the basis of the results of simulation, the results of improved AFDPF algorithm are analyzed. Finally, the advantages and disadvantages are summarized.

Hierarchical hybrid filing system is a research hotspot in the field of data storage, and also is widely accepted in the industrial circle, which is widely used from personal storage to data center. This paper introduces an energy-efficient optical storage at a lower cost to solve the energy consumption problem of large data center, with an attempt to build a hybrid filing system comprised of array, online optical disk library and off-line optical disk library, discusses the guarantee mechanism of data consistency and the elastic design of system, and focuses on the research of the file caching and prefetching mechanism of hybrid magneto-optical filing system based on the read-write features of optical medium. Through experiments, the system is proved to be capable of effectively saving energy and maintaining the timeliness of data retrieval and query.

With the ceaseless propulsion of informatization process, a great deal of data accumulated in the production system resulted in archiving demand; meanwhile, with the increasingly enriching types of data information, big data technology enhanced the function of unstructured data. This paper designs and realizes the KingCloud intelligent object archiving system, which achieves classification of text files through document classification technology and provides logic views of documents and achieves the acquisition of content elements through image identification, video keyframe and other technologies. As for the overall storage structure, document prefetching, memory buffer, data layout and strategy perception etc. can be optimized by combining the semantic studies of file system, and data can be intelligently classified, summarized, discovered, predicted and analyzed to remarkably improve the service ability, service quality and service performance of memory system.

Based on the GCr15 SEM digital metallographic image, an efficient approach for quantitative analysis processing by Matlab software is introduced in this work, gray scale, adjusting the gray, and morphologic operation in digital image processing are used to estimate proportion of the carbide particle and to evaluate the quality of quenching and tempering heat treatment for GGr15 bearing steel. We found that the carbide particle of quenched and tempered GCr15 in bearing outer ring is less than that in the tapered roller, meaning that they will have different mechanical property in future.

Colorectal neoplasm is considered to have a strong association with nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), respectively. The relationship among NAFLD, MetS, and colorectal neoplasm was assessed in 1793 participants. Participants were divided into 4 groups based on the status of NAFLD and MetS. Relative excess risks of interaction (RERI), attributable proportion (AP), and synergy index (SI) were applied to evaluate the additive interaction. NAFLD and MetS were significantly correlated with colorectal neoplasm and colorectal cancer (CRC), respectively. The incidence of CRC in NAFLD (+) MetS (+) group was significantly higher than other 3 groups. The result of RERI, AP, and SI indicated the significant additive interaction of NAFLD and MetS on the development of CRC. NAFLD and MetS are risk factors for colorectal neoplasm and CRC, respectively. And NAFLD and MetS have an additive effect on the development of CRC.

According to the specific market condition of liquor industry, a new wireless monitoring system based on zigbee wireless data transmission technology and labview programming environment is put forward in this paper. Combined zigbee with labview, it make human-computer interaction interface more simple, show more intuitive. In the actual application, this way can greatly shorten the development cycle and reduce consumption. The paper is composed of, the system’s structure, the hardware and the software design.

In conventional continuous polishing process, the surface shape of work-piece was measured by an optical plane template after being placed in such environment with constant temperature for 1 to 2 hours. During this period, uncertain influence may occur on the polishing pad due to the change of system state. Meanwhile, the regular off-line testing may cause re-processing. In this paper, a new method about on-line monitoring surface shape of optical elements is proposed by the theory of run sphere, and the change in curvature radius of the work-piece which lead to its radial tilt angle change. The change in work-piece surface shape indirectly obtain by the correction plate small angle with respect to the horizontal, and the angle were detected on line by the high-precision goniometer with the resolution 0.04 ''. According to theoretical calculations, the diameter of 200mm precision work-piece PV value up to 0.02λ (λ = 632.8nm). The fused quartz glass was measured by above method. The test results showed that the surface accuracy and processing efficiency were significantly promoted, and also improving the controllability of surface shape of work-piece based on this method.

The aim of the present study was to investigate the protective mechanism underlying of melatonin in severe acute pancreatitis (SAP). A total of 64 male Sprague‑Dawley rats were randomly divided into four groups: The sham operation (SO) group, SAP group, melatonin treatment (MLT) group and p38 inhibitor (SB203580) treatment (SB) group. Acute pancreatitis was induced by 5% taurocholate through retrograde infusion into the biliopancreatic ducts. The melatonin and SB203580 treatment groups were administered with MLT and SB 30 min before operation the induction of SAP. Rats in each group were euthanized at 6 and 12 h following SAP induction. Blood and pancreatic tissues were removed for inflammatory examination. Peripheral blood mononuclear cells (PBMCs) were isolated following sacrifice to measure the phosphorylation of p38 and nuclear factor‑κB (NF‑κB was measured as p65 and phosphorylation of p65). The pretreatment of melatonin significantly attenuated the severity of pancreatitis. In addition, melatonin also reduced serum amylase and proinflammatory cytokine levels, including tumor necrosis factor‑α, interleukin (IL)‑1 and IL‑6. The mean pathological scores for pancreatic tissues in the MLT group were higher than those for samples in the SO group, but were lower than those for samples in the SAP group at each time-point. Phosphorylation of p38 and p65 levels in the melatonin treatment group were lower than that in the SAP group, and higher in the SAP group than in the SO group, and the SB203580 treatment group. Furthermore, melatonin significantly inhibited the activation of p38 and NF‑κB in PBMCs. The authors revealed that melatonin may attenuate inflammatory reactions by inhibiting the activation of p38 MAPK and NF‑κB in both acute pancreatitis rats and PBMCs. SAP is a severe disease with a high risk of morbidity and mortality. It is important to attenuated inflammatory reaction in acute pancreatitis. Thus, the authors studied melatonin, which is synthesized by the pineal gland and released into the blood. Previous studies have shown that melatonin serves a protective role in the early course of human acute pancreatitis, and melatonin concentration variations are closely related to the severity of acute pancreatitis. It may be concluded that melatonin may attenuates inflammatory reactions by inhibiting the activation of p38 MAPK and NF‑κB in both acute pancreatitis rats and PBMCs.

Background Whether melatonin receptor 1B (MTNR1B) variants are associated with type 2 diabetes mellitus (T2DM) remains unclear. Therefore, we performed this meta‐analysis to better explore correlations between MTNR1B variants and T2DM. Methods Literature research was performed in PubMed, Medline, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results Totally 21 studies were enrolled to analyses. Pooled overall analyses showed that MTNR1B rs10830963 variant was significantly correlated with the susceptibility to T2DM (allele model: p = 0.02, OR = 0.97, 95% CI 0.95–1.00). Further subgroup analyses by ethnicity of participants revealed that rs10830963 variant was significantly correlated with the susceptibility to T2DM in South Asians, but not in Caucasians or East Asians. No any other positive results were found in overall and subgroup analyses. Conclusions Our findings indicated that MTNR1B rs10830963 variant might serve as a genetic biomarker of T2DM, especially in South Asians.

Recent studies have demonstrated that melatonin significantly decreased all studied acute pancreatitis-associated inflammatory parameters, in addition to reducing apoptosis and necrosis associated with pancreatic injury. However, the effect of melatonin on gut barrier dysfunction and bacterial translocation has not been fully elucidated. This study aimed to investigate the protective effects of melatonin on intestinal integrity in a rat model of severe acute pancreatitis (SAP) to evaluate whether melatonin prevented intestine barrier dysfunction and reduced bacterial translocation. Forty male Sprague Dawley (SD) rats were randomly divided into three groups, with 8 rats in the sham operation (SO) group, 18 rats in the SAP group and 14 SAP rats in the melatonin treatment (MT) group. SAP was induced by retrograde injection of 4% taurocholate into the biliopancreatic duct. Melatonin was administered 30 min prior to taurocholate injection in the melatonin-treated rats. All rats were sacrificed 24 h subsequent to pancreatitis induction. Real-time fluorescence quantitative polymerase chain reaction was used to detect and quantify Escherichia coli (E. coli) O157 in postcava blood. The microvilli structure was also analyzed with transmission electron microscopy. The level of E. coli DNA in the MT group was significantly lower than in rats in the SAP group. No E. coli DNA was detected in the control group. Villus height and crypt depth in the ileum were significantly higher in the MT and control groups compared to the SAP group, and were significantly higher in the MT group than in the SAP group. These results suggested that melatonin prevented gut barrier dysfunction and reduced bacterial translocation, resulting in reduced pancreatic-associated infections and decreased early mortality rates.

In order to mend cutting instability of ball-end milling cutter caused by the changes of cutting loads in high speed milling hardened steel, we perform the modal analysis and heat-force coupling field analysis of cutter, carry out the experiment of high speed milling hardened steel, investigate the character and effect factor of physical field distribution in high speed ball-end milling hardened steel, and propose the method about the match of diameter and overhang for depressing cutter vibration. Results indicate that the decrease in the ratio of overhang to diameter can transform the first modal shape of cutter from bending modal shape into torsion modal shape. The diameter of cutter is from 30mm to 20mm, the overhang of cutter is from 125mm to 90mm, heat-force coupling field distribution changes slightly, resonance of cutter does not occur, and efficiency in machining hardened steel can be improved effectively by higher cutting speed.

Based on detailed 3D finite element (FE) analyses, idealized and non-idealized axial through-wall flaws were evaluated in a cylinder under internal pressure. The key parameters (Stress Intensity Factor, Reference stress, and Crack Opening Area) from widely accepted structural integrity assessment procedures (BS 7910 and API 579-1/ASME FFS-1) were explored and compared between idealized (perpendicular straight-sided flaw) and non-idealized geometry. The effect of crack shape on the evolution of stress intensity factors and crack opening areas along the crack front were also investigated. Non-idealized crack shapes have been modelled assuming a straight crack front with different internal and external crack lengths. The influence of crack shape has been evaluated by varying the crack front location and lengths ratios. The current findings highlight the significance of assessing a more realistic crack shape and should be considered in a leak-before-break (LBB) analysis. A non-idealized crack has a significantly smaller crack opening area than the equivalent idealized through-wall crack. Therefore the leakage rate at this stage of crack growth will be lower than predicted by standard solutions. Stress intensity factor solutions should also take the crack shape variation into account with regards to fatigue crack growth as a surface flaw propagates through-thickness.

One of the ways to aid the decision whether or not to live with defects in pressurised components is through the demonstration of Leak-Before-Break (LBB). In this paper, three of the main solutions to carry out the LBB assessment, namely Stress Intensity Factor (SIF), Reference Stress (RS) and Crack Opening Area (COA) have been evaluated and compared for both BS 7910 and API 579/ASME FFS-1 standards. Differences with respect to the choice of solutions and boundary conditions are illustrated and discussed. The same applied loads and material properties have been used when applying each procedure. Different geometries for potential pressurised components which are of interest with regards to LBB have been considered for each solution. Focus is made on cylinders where axially and circumferentially oriented through-wall and surface cracks were analysed. While SIF solutions produce similar results for both standards, reference stress solutions show greater differences in the results. However, in LBB assessments it is the reference stress solution which is more relevant, since most LBB assessments pre-suppose the material to be ductile. In terms of COA, solutions are not given exactly equivalent, however they seem to agree well within the common range of applicability. Differences in the assessment route between the standards is also discussed. Experimental data from literature has also been compared to the different standard predictions, to illustrate the accuracy of the solutions for axially oriented surface cracks. The ability of solutions to predict the boundary between leak and break is discussed, in relation to how this shows the level of conservatism.

Simulations analysis of the aerodynamic for a sports car modeling before and after optimization was introduced in the paper by using commercial CFD code--STAR-CCM+. In the first simulation, we got the drag coefficient, the pressure of convective and the turbulent kinetic energy spectrum，then we found the positions that may affect the drag coefficient. Further analysis inferred that our modifications accorded with the aerodynamic principles. These results can provide the basis for the modeling design and further optimization.

According to the components, mechanical properties of difficult-to-process material (26NiCrMoV145)as well as characteristics of high-speed machining, modelling and prediction of cutting force in high-speed milling is studied. Based on geometry model of ball end mill edge line, milling force model of helical ball milling cutter is established by theoretical analysis and empirical coefficient. Then, simulation prediction of cutting forece is conducted under different circumstances. The experimental result shows that the predicted cutting force is consistent with experimental data and the established model is reasonable. The article contributes to the milling of difficult-to-process material, which improves security and productive efficiency in processing.

Objectives This study aims to investigate the relationship between the protective effects of melatonin in pancreas and the expression of sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA) and Na + /Ca 2+ exchanger (NCX) in rats with acute necrotizing pancreatitis (ANP), to verify whether melatonin ameliorates ANP by alleviating calcium overload. Methods Ninety-six male Sprague-Dawley rats were randomly divided into four groups (sham operation group, ANP group, melatonin treatment group, melatonin contrast group). ANP was induced by the retrograde injection of 4% taurocholate (1 ml/kg body weight) into the biliopancreatic duct. Melatonin (50 mg/kg body weight) was administered 30 min before the induction of ANP in the melatonin treatment group. Rats in each group were euthanized at 1, 4, and 8 h after ANP induction. Pancreatic tissues were removed to measure SERCA and NCX levels and cytosolic calcium ion (Ca 2+ ) concentration ([Ca 2+ ] i ). Results At each time point, SERCA and NCX levels in the melatonin treatment group were significantly higher than that in the ANP group, and lower than that in the sham group and the melatonin contrast group. These levels did not differ between the 4- and 8-h time points in the ANP group. [Ca 2+ ] i in pancreatic acinar cells was higher in the melatonin treatment group than in the sham group and the melatonin contrast group, but lower than in the ANP group, at each time point. Conclusion Melatonin can reduce pancreatic damage via the up-regulation of SERCA and NCX expression, which can alleviate calcium overload in pancreatic acinar cells.

It’s very difficult to machine titanium alloy because of its features of small deformation coefficient, low thermal conductivity, small elastic modulus and large chemical activity. In this paper, we take titanium alloy TC4 as an example; using the finite element method (FEM) for the physical simulation of milling process, analyze the impact of some tool geometric parameters, such as rake angle, relief angle, rounded cutting edge radius etc., on chip form, cutting force, cutting temperature distribution of cutting tool and the maximum cutting temperature of rake face etc.. On this basis, we choose the best tool geometries, which can be taken as a theoretical reference for developing process plans of titanium alloy to reduce the number of tests and costs of field trials and to improve productivity.

In the current paper, three different constitutive models are employed for the analysis of laminar MRF (MagnetoRheological Fluid) flows between two parallel plates. The capability of a recently constructed non-convex constitutive model is compared with those of widely used Bingham model and Herschel-Bulkley model. The comparison among simulated flow velocity distributions and shear stress - shear strain rate characteristics based on different models is presented. It is shown that the non-convex consitutive model outperformance the other two models.

A noncontact inspection system for gear based on machine vision is developed in this work, according to the mathematical model of lens distortion; the calibration of the camera was realized by the MATLAB calibration toolbox, obtained the distortion coefficients, by which the pixel is proofread. After then the key parameters of gear could be automatically acquired with proposed algorithm. In this work, the algorithm is applied to a practical case of a standard spur gear; the experimental results reported here confirm the effectiveness of the approach.

A novel faint signal processing method based on phase-lock amplification principle is developed to enhance the sensitivity of pump/probe-based laser generated and laser detected surface acoustic waves (LG/LD SAW) spectroscopy system. This novel method involves a “dead zone” filter located before a common phase-lock amplification unit, which wipes off most of the noise stacked on SAW signal. This paper explored the working principle of this novel signal processing method based on the knowledge of the characteristics of the system noise and the signal. The experiment result shows that the detection system’s sensitivity has been dramatically improved by this new signal processing method.

During May 12th 2008 Wenchuan earthquake with the magnitude of 8.0, a 4-span rigid frame arch bridge named as Xiaoyudong Bridge which situated close to the epicenter was hit by strong ground motion and was severely damaged. The earthquake response analysis of the bridge was made using FE software MIDAS based on recorded ground motion during the Wenchuan earthquake in this paper. The study showed that the main and minor arch legs on the both ends piers were weak links which may be damaged firstly under strong ground motion. The next damage at the pier with weakest horizontal stiffness is one of the important reasons causing the bridge collapsed. This paper will introduce our work on those respects and some drawn conclusions.

The damage of bearing will change the boundary condition for whole bridge, if we do not take account of bearing failure, the error of structural analysis and the unreasonable in design will be made. In this paper, the effect of possible bearing damage to whole bridge during strong ground motion is studied through examining the seismic performance of a multi-span continuous girder bridge which is a real damaged bridge during the Wenchuan earthquake in 2008. Proper analytical restoring force models of bearings are proposed, which can simulate the seismic performance of the bridge before and after the bearing damage suitably.