High preoperative white blood cell count determines poor prognosis and is associated with an immunosuppressive microenvironment in colorectal cancer

BackgroundThe correlation between high white blood cell (WBC) count and poor prognosis has been identified in various types of cancer; however, the clinical significance and immune context of WBC count in colorectal cancer remains unclear.MethodsBetween February 2009 and November 2014, 7,433 patients at the Shanghai Cancer Center who had undergone elective surgery for colorectal cancer were enrolled in this retrospective cohort study. Patients were divided into two groups: low and high preoperative WBC groups. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan–Meier method and Cox regression analysis were used to identify independent prognostic factors in colorectal cancer patients. Tumor-infiltrating immune cells in the high and low preoperative WBC groups were compared using immunohistochemical staining.ResultsOf the 7,433 patients who underwent colorectal cancer surgery and were available for analysis, 5,750 were included in the low preoperative WBC group, and 1,683 were included in the high preoperative WBC group. After propensity score matching, 1,553 patients were included in each group. Kaplan–Meier survival curves showed that a high preoperative WBC count was associated with a decreased overall survival (P = 0.002) and disease-free survival (P = 0.003), and that preoperative WBC count was an independent risk factor for overall survival (hazard ratio, 1.234; 95% confidence interval, 1.068–1.426; P = 0.004) and disease-free survival (hazard ratio, 1.210; 95% confidence interval, 1.047–1.397, P = 0.01). Compared to the low preoperative WBC group, the high preoperative WBC group exhibited higher expression of regulatory T cells (P = 0.0034), CD68+ macrophages (P = 0.0071), and CD66b+ neutrophils (P = 0.0041); increased expression of programmed cell death protein 1 (P = 0.005) and programmed cell death ligand 1 (P = 0.0019); and lower expression of CD8+ T cells (P = 0.0057) in colorectal cancer patients.ConclusionsOur research indicates that a high preoperative WBC count is a prognostic indicator in colorectal cancer patients and is associated with an immunosuppressive tumor microenvironment, which could aid in future risk stratification

Collaborative collection effort strategies based on “Internet + recycling” business model

"Internet + recycling", a new and emerging collecting mode, is booming in conjunction with widespread Internet use in China. For the recycling of waste electrical and electronic equipment (WEEE), this paper studies collaborative collection effort strategies in a collection system consisting of a third-party and an e-tailer based on the "Internet + recycling" business model. Considering the collaboration occurring during collecting and selling and mutual influences of partners on the recycling of old products, the paper applies collection effort cost sharing mechanisms to promote recycling. Four models, namely, the centralized model (C-Model), unit transfer price model (P-Model), unilateral cost sharing model (U-Model) and bilateral cost sharing model (B-Model), are established, and optimal decisions and members' profits in various collaborative models are derived and compared. The results show that there exists an interval of profit sharing proportions in which each of the two cost sharing models is a Pareto improvement of the P-Model, and the total collection volume and profit of the collecting system increase in the B-Model relative to those in the U-Model under the same proportion of profit sharing. However, the B-Model is not necessarily a Pareto improvement of the U-Model. The results also show that profit improvements of both parties can be achieved without the third-party sharing the e-tailer's collection effort cost in the B-Model when the collaborative marginal profit is large enough. The paper further explores the impact of the collaborative marginal profit and third-party's market influence on the total collection volume and the efficiency of the collecting system. This study provides insight into the promotion of WEEE recycling and into the selection of collaborative strategies for Internet recycling enterprises. The work will prove beneficial to the development of the WEEE "Internet + recycling" industry

Creación y Simulación de Metodologías de Análisis, Clasificación e Integración de Nuevos Requerimientos a Software Propietario

La priorización de nuevos requerimientos a implementar en un software propietario es un punto fundamental para su mantenimiento, la conservación de la calidad, observación de las reglas de negocio y los estándares de la empresa. Aunque existen herramientas de priorización basadas en técnicas probadas y reconocidas, las mismas requieren una calificación previa de cada requerimiento. Si la empresa cuenta con solicitudes provenientes de varios clientes de un mismo producto, aumentan los factores que afectan a la empresa, las herramientas disponibles no contemplan estos aspectos y hacen mucho más compleja la tarea de calificación. Este trabajo de investigación abarca la realización de un relevamiento de los métodos de priorización y selección de nuevos requerimientos utilizados por empresas de la zona de Rosario, y la definición de una metodología para la selección un nuevo requerimiento, que implica el análisis y evaluación de todas las implicaciones sobre el producto de software y la empresa, respetando sus reglas de negocio. La metodología creada conduce a la definición de los procesos para la construcción de una herramienta de calificación y priorización de nuevos requerimientos en software propietario que tiene solicitudes de varios clientes al mismo tiempo, con instrumentos de calificación que consideran todos los aspectos relacionados, proveerá técnicas de priorización actuales y emitirá informes personalizados según diferentes perspectivas de la empresa.Eje: Ingeniería de SoftwareRed de Universidades con Carreras en Informática (RedUNCI

Design and Implementation of Freeway Infrastructure Safety and Emergency Management System

AbstractAs an important content of freeway safety management, the freeway infrastructure safety and emergency management system can bring great social effect. In this article, a comprehensive freeway infrastructure safety and emergency management system was built by following steps: firstly, research significance, research status and the paper framework were illustrated. Secondly, in allusion to five kinds of transportation infrastructure: pavement, bridge, tunnel, side slope and ancillary facility, the existing infrastructure testing indexes were summarized, and the relations between traffic safety and these testing indexes were quantified. Thirdly, according to the different characteristic of five kinds of infrastructures, comprehensive safety evaluation models were proposed in order to evaluate the safety of freeway infrastructure. Fourthly, the system of emergency management and emergency plans were expounded. Finally, the system software was developed on the base of research about system framework, database system and Web GIS technology. This system has strong practicability, which can compensate for the deficiencies of the infrastructure detection in the past and provide a new informationalized management platform for freeway management

Study on Fatigue Characteristics of Bionic Functional Surface of Hardened Steel

In this study, we aimed to process the biomimetic function surface by designing a prototype for modeling the pits on a dung beetle body and the abdomen of a desert viper, and by using high speed milling and controlling the ratio of row spacing to feed rate. Firstly, we conducted three-dimensional parametric modeling and static analysis of the bionic functional surface using 3D modeling software UGNX (12.0, SIEMENS AG, Munich, Germany) and finite element analysis software ABAQUS (2018, Dassault, Providence, RI, USA). Then, the analysis results were imported into the fatigue life analysis software nCode (2018, HBM United Kingdom Ltd., South Yorkshire, UK) to simulate the fatigue characteristics of different bionic pit morphology models. Per the simulated tensile fatigue testing machine, the result shows that the minimum fatigue life value of the quadrilateral pit surface of the simulated dung beetle is one and four times higher than the hexagonal pit morphology and the irregular pit morphology, respectively, whereas the maximum fatigue damage is lower by one and five orders of magnitude, respectively. The quadrilateral pit surface on the biomimetic dung beetle body has better fatigue resistance, which can considerably improve the fatigue damage distribution state and the fatigue life of hardened steel die surfaces. The influential regulation of milling parameters on fatigue performance was studied and the results show that the fatigue resistance of the model is optimal when milling parameters are: row spacing of 0.4 mm, loading space of 0.2 mm, and milling depth of 0.3 mm. The quadrilateral dimensions formed by milling are highly similar to those of a dung beetle body proving that a certain reduction in milling process depth can increase the structural fatigue resistance. From the perspective of fatigue crack growth analysis, the quadrilateral dimples on the surface of the dung beetle improve fatigue crack growth inhibition and fatigue resistance

Identification of a Chromosome 1 Substitution Line B6-Chr1BLD as a Novel Hyperlipidemia Model via Phenotyping Screening

Hyperlipidemia is a chronic disease that seriously affects human health. Due to the fact that traditional animal models cannot fully mimic hyperlipidemia in humans, new animal models are urgently needed for basic drug research on hyperlipidemia. Previous studies have demonstrated that the genomic diversity of the wild mice chromosome 1 substitution lines was significantly different from that of laboratory mice, suggesting that it might be accompanied by phenotypic diversity. We first screened the blood lipid-related phenotype of chromosome 1 substitution lines. We found that the male HFD-fed B6-Chr1BLD mice showed more severe hyperlipidemia-related phenotypes in body weight, lipid metabolism and liver lesions. By RNA sequencing and whole-genome sequencing results of B6-Chr1BLD, we found that several differentially expressed single nucleotide polymorphism enriched genes were associated with lipid metabolism-related pathways. Lipid metabolism-related genes, mainly including Aida, Soat1, Scly and Ildr2, might play an initial and upstream role in the abnormal metabolic phenotype of male B6-Chr1BLD mice. Taken together, male B6-Chr1BLD mice could serve as a novel, polygenic interaction-based hyperlipidemia model. This study could provide a novel animal model for accurate clinical diagnosis and precise medicine of hyperlipidemia

HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation

HOXC6 plays an essential part of the carcinogenesis of solid tumors, but its functional relevance within the immune contexture in patients with colorectal cancer (CRC) is still uncertain. We intended to investigate the predictive value of HOXC6 expression for survival outcomes and its correlation with immune contexture in CRC patients by utilizing the Cancer Genome Atlas database (n = 619). Validation was performed in cohorts from Zhongshan Hospital (n = 200) and Shanghai Cancer Center (n = 300). Immunohistochemical (IHC) staining was utilized to compare the levels of immunocytes infiltrating the tumor between the groups with high and low expression of HOXC6. Elevated levels of HOXC6 expression in CRC tissues were linked to malignant progression and poor prognosis. HOXC6 as a risk factor for survival of CRC patients was confirmed. Receiver operating characteristic analysis confirmed its diagnostic value, and a reliable prognostic nomogram was constructed. KEGG analysis and GSEA showed that HOXC6 participated in immune regulation, and its expression was tightly linked to the abundance of infiltrating immunocytes. HOXC6 was upregulated in patients diagnosed with CRC within the two cohorts, and high HOXC6 levels were correlated with a worse prognosis. The high-HOXC6 expression group showed increased infiltration of Treg cells, CD68+ macrophages, CD66b+ neutrophils, and CD8+ T-cells and elevated levels of PD-L1 and PD-1, but decreased levels of granzyme B and perforin. These findings suggest that HOXC6 abundance in patients with CRC determines a poor prognosis, promotes an immunoevasive environment, and directs CD8+ T-cell dysfunction. HOXC6 is expected to become a prospective biomarker for the outcome of CRC

Correction to: Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging

Unfortunately, after publication of this article [1], it was noticed that the order of correspondence addresses was reversed. Maosheng Xu should be listed before Minli Chen. The correct order of correspondence can be seen in this correction article

Maternal Vitamin A deficiency during pregnancy and lactation induced damaged intestinal structure and intestinal flora homeostasis in offspring mice

Abstract The small intestine serves as the first channel of dietary Vitamin A (VA) and the unique organ of VA absorption and metabolism. However, there have not been extensive investigations on the exact mechanisms within VA‐related changes in intestinal metabolic disorders. This research is designed to analyze whether and how VA affects intestinal metabolic phenotypes. Male C57BL/6 mice after weaning were randomly fed a VA control diet (VAC) or a VA‐deficient diet (VAD) during the entire pregnancy and lactation process. After a total of 11 weeks, cohorts of VA deprived were next fed to a VA control diet (VAD‐C) for another 8 weeks. The concentration of retinol was measured by a high‐performance liquid chromatography system. The 16S gene sequencing was used to evaluate the intestinal microbiota changes. Through the use of histological staining, western blots, quantitative PCR, and enzyme‐linked immunosorbent assays, the intestinal morphology, inflammatory factors, and intestinal permeability were all evaluated. Following the decrease of the tissue VA levels, VAD mice show a decrease in tissue VA levels, community differences, and the richness and diversity of intestinal microbiota. VAD diet‐driven changes occur in intestinal microbiota, accompanied by a higher mRNA expression of intestinal inflammatory cytokines and an increase in intestinal permeability. As dietary VA is reintroduced into VAD diet‐fed mice, the tissue VA levels, inflammatory response, and intestinal homeostasis profiles are all restored, which are similar to those found after the occurrence of VA‐controlled changes within intestinal microbiota. VA deficiency caused the imbalance of intestinal metabolic phenotypes through a mechanism involving changes in intestinal microbiota. It is thought that intestinal microbiota metabolic influences represent a new salient and additional mechanism, which can be used as a new method to achieve the onset and treatment of the effect of VAD on intestinal homeostasis impairment