Development and validation of novel inflammatory response-related gene signature for sepsis prognosis

Due to the low specificity and sensitivity of biomarkers in sepsis diagnostics, the prognosis of sepsis patient outcomes still relies on the assessment of clinical symptoms. Inflammatory response is crucial to sepsis onset and progression; however, the significance of inflammatory response-related genes (IRRGs) in sepsis prognosis is uncertain. This study developed an IRRG-based signature for sepsis prognosis and immunological function. The Gene Expression Omnibus (GEO) database was retrieved for two sepsis microarray datasets, GSE64457 and GSE69528, followed by gene set enrichment analysis (GSEA) comparing sepsis and healthy samples. A predictive signature for IRRGs was created using least absolute shrinkage and selection operator (LASSO). To confirm the efficacy and reliability of the new prognostic signature, Cox regression, Kaplan-Meier (K-M) survival, and receiver operating characteristic (ROC) curve analyses were performed. Subsequently, we employed the GSE95233 dataset to independently validate the prognostic signature. A single-sample GSEA (ssGSEA) was conducted to quantify the immune cell enrichment score and immune-related pathway activity. We found that more gene sets were enriched in the inflammatory response in sepsis patient samples than in healthy patient samples, as determined by GSEA. The signature of nine IRRGs permitted the patients to be classified into two risk categories. Patients in the low-risk group showed significantly better 28-d survival than those in the high-risk group. ROC curve analysis corroborated the predictive capacity of the signature, with the area under the curve (AUC) for 28-d survival reaching 0.866. Meanwhile, the ssGSEA showed that the two risk groups had different immune states. The validation set and external dataset showed that the signature was clinically predictive. In conclusion, a signature consisting of nine IRRGs can be utilized to predict prognosis and influence the immunological status of sepsis patients. Thus, intervention based on these IRRGs may become a therapeutic option in the future.

     

Global changes of 5-hydroxymethylcytosine and 5-methylcytosine from normal to tumor tissues are associated with carcinogenesis and prognosis in colorectal cancer

Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal cancer (CRC) and their association with the prognosis. The levels of genomic 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in cancerous tissues were significantly lower than those in corresponding adjacent normal tissues. The genomic levels of 5mC were significantly positively correlated with 5hmC in normal and cancerous tissues (all P<0.05). The ratio of 5mC in cancerous tissues to matched normal tissues (C/N-5mC) was also significantly positively correlated with the ratio of 5hmC in cancerous tissues to matched normal tissues (C/N-5hmC) (P=0.01). The 5mC levels and C/N-5mC ratios decreased with age (all P<0.05). Higher 5mC and 5hmC levels were found in rectal than in colon tissues (all P<0.05). High levels of 5mC in cancerous tissues and high C/N-5hmC ratios were each associated with lymph node metastasis (all P<0.05). Survival analysis indicated that the C/N-5mC ratio (P=0.04) is an independent protective factor for overall survival. The data showed that patients with a combination of high C/N-5hmC and low C/N-5mC ratios tended to have a worse prognosis (P<0.01). Our findings showed that the C/N-5mC ratio may be an independent prognostic factor for CRC outcome. Patients with both a high C/N-5hmC ratio and a low C/N-5mC ratio exhibited the worst survival, suggesting that 5mC and 5hmC can be used as critical markers in tumorigenesis and prognosis estimation.     

HER-2 overexpression and survival in colorectal cancer: a meta-analysis

Objective

Numerous studies examining the relationship between human epidermal growth factor receptor 2 (HER-2) overexpression and survival in patients with colorectal cancer (CRC) have yielded controversial results. We therefore performed a meta-analysis more precisely to estimate its prognostic value.

Methods

Published studies investigating the effect of HER-2 overexpression on CRC survival were identified; the hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were pooled in terms of disease-specific or overall survival.

Results

Eleven studies were included in the meta-analysis. The pooled data showed that HER-2 overexpression was negatively related to CRC survival (HR=1.10, 95% CI: 0.77–1.44). Subgroup analyses regarding test method and study quality also demonstrated little association between HER-2 overexpression and CRC survival (HR=0.89, 95% CI: 0.50–1.29; HR=0.90, 95% CI: 0.43–1.37, respectively).

Conclusions

Regardless of several limitations, our study suggested that HER-2 overexpression probably had little impact on CRC survival.     

Mobile response system: a novel approach to interactive and hands-on activity in the classroom

Mobile devices are being used profusely in the classrooms to improve passive learning environments and to enhance student comprehension. However, with respect to students’ active involvement in problem solving activities, the typical usage of the mobile devices in answering multiple choice and true/false questions is not adequate and the use of mobile devices need to be expanded to include dynamic and interactive problem-solving activities to better satisfy students’ learning needs. To facilitate such interactive problem solving using mobile devices, a comprehensive software environment is necessary. This paper details the design, deployment and evaluation of Mobile Response System (MRS) software that facilitates execution and assessment of multi-step in-class interactive problem-solving activities using mobile devices. MRS is an active learning tool, which engages students with the visual representation of a problem that spans on multiple screens, allows them to interact with that, and makes them realize the consequences of their actions instantly and visually. The immediate and automated grading feature of MRS enables a feedback-driven and evidence-based teaching methodology, which is important to improve the quality of classroom learning. MRS is designed to be independent of any interactive problem or its domain. Therefore, it allows easier integration of interactive activity Apps developed by others and can be used in any discipline. The results obtained from software metrics and runtime performance data verified the quality of the software. Additionally, the in-class assessment data verified that the MRS software is a helpful intervention for improving student comprehension and satisfaction.     

Erratum to: Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation

Journal of Zhejiang University-SCIENCE B - The original version of this article unfortunately contained a mistake. In p.605, the number of the Zhejiang Provincial Natural Science Foundation of...     

E-钙粘素与大肠癌侵润转移的关系

[目的]探讨E-钙粘素(E-Cad)表达与大肠癌发生发展及预后的关系.[方法]采用S.P免疫组织化学染色技术,检测30例大肠腺瘤,60例大肠癌组织E-Cad的表达情况.[结果]E-Cad的表达率在大肠腺瘤中为87.10％,显著高于大肠癌中的55.00％(P相似文献   

外泌体来源的半乳糖凝集素-9预测肝移植术后排斥发生及预后（英文）

目的:外泌体及其内容物是各种肝脏疾病的潜在生物标志物。本研究探索外泌体及其内容物在肝移植排斥反应及预后中的作用。创新点:本研究发现外泌体及内含物半乳糖凝集素-9(galectin-9)在肝移植术后排斥及预后预测中发挥重要作用。方法:分别从急性排斥和肝功能稳定患者提取外泌体,进行分离、鉴定并检测其内含蛋白。候选蛋白通过在73个急性排斥病人和63个肝功能稳定病人切除肝的组织芯片中进行验证。最后将蛋白表达量和临床参数纳入Kaplan-Meier生存率和Cox回归分析。结论:外泌体来源的galectin-9可作为预测肝移植术后排斥发生及预后的生物学指标。     

Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation

Journal of Zhejiang University-SCIENCE B - Acute cellular rejection (ACR) remains a major concern after liver transplantation. Predicting and monitoring acute rejection by non-invasive methods are...     

HER2 over-expression and response to different chemotherapy regimens in breast cancer

Purpose To exam the relationship between HER2 over-expression and different adjuvant chemotherapies in breast cancer. Patients and Methods A total of 1625 primary breast cancer patients who received post-surgery adjuvant chemotherapy in Tianjin Cancer Hospital, China, from July 2002 to November 2005 were included in the study. Among them, 600 patients were given CMF (CTX MTX 5-Fu) regimen, 600 given CEF (CTX E-ADM 5-Fu) regimen, and 425 given anthracyclines plus taxanes regimen, with mean follow-up time of 42 months. Results In CMF treatment group, the 3-year disease free survival (DFS)in HER2 over-expressed patients was lower than that of the HER2-negative ones (89.80% vs 91.24%, P=0.0348); in node-positive subgroup, the 3-year DFS was 84.72% in HER2 over-expressed patients, and 90.18% in the HER-2-negative ones (P=0.0271).Compared to CMF regimen, anthracyclines and anthracyclines plus taxanes regimens are more effective (P＜0.05) in node-positive HER2 over-expression than those in the node-negative. Conclusion HER2 over-expression is an independent index for predicting poor prognosis and short DFS for breast cancer patients. HER2 over-expressed patients are resistant to CMF regimen chemotherapy, but sensitive to anthracyclines-based or anthracyclines plus taxanes regimen. HER2 expression can be taken as a marker for therapies in breast cancer.     

MACC1 upregulation promotes gastric cancer tumor cell metastasis and predicts a poor prognosis

In various studies, metastasis associated with colon cancer 1 (MACC1) has been frequently reported to be abnormally highly expressed in human lung cancer, colon cancer, and hepatocellular carcinoma. Our study focuses on the association of MACC1 expression with gastric cancer (GC). During our experiment, the MACC1 expression was tested in 105 GC samples using an immunohistochemical (IHC) method. The clinical characteristics and prognosis of these patients were summarized. During analysis, MACC1 distribution in GC samples with distant metastasis was higher than that in normal samples and in tumors with no dissemination. Subsequently, a lower 5-year survival rate had a strong correlation with high MACC1 expression. As a consequence, the present results suggest that MACC1 is more frequently expressed in a poor prognosis phenotype of GC and acts as a promising prognostic prediction parameter for GC.     

Development and evaluation of a novel e-book interface for scaffolding thinking context to learn from writing examples

Effective reading strategies, including using graphic organizers, question answering, and considering story structures, can help students improve reading comprehension. However, these reading strategies are not fully supported by both printed books and e-books. Students who master these reading strategies can learn effectively. By contrast, students without effective reading strategies cannot grasp thinking contexts, which leads to unfavorable learning outcomes. This paper presents a novel e-book interface that features thinking maps and a question answering mechanism on the same page. The thinking maps and question answering mechanism can stimulate students to reflect on reading content, which in this study was college entrance exam compositions, and help students to more effectively understand the context of their reading content. After we developed our reading system, 61 participants were recruited for system evaluation. The results indicate that students in the treatment group acquired significantly more vocabulary and understood the story structure more competently than did students in the control group. Treatment group participants expressed that they were satisfied with the thinking maps and question answering mechanism.     

Use of standardized test scores to predict success in a computer applications course

The purpose of this study was to see if a relationship existed between American College Testing (ACT) scores (i.e., English, reading, mathematics, science reasoning, and composite) and student success in a computer applications course at a Mississippi community college. The study showed that while the ACT scores were excellent predictors of success, the ACT scores did not predict nonsuccess. Inclusion in the nonsuccess group is only slightly accounted for in the models by use of either ACT composite score or ACT subscores; therefore, there must be other factors that affect the student outcome in the course. However, the odds ratio indicated that for every one point of increase in ACT composite score, a student is 18% more likely to be successful in the computer applications course. Likewise, a student is 11.9% more likely to be successful in the computer applications course for every one point of increase on ACT science reasoning score.     

High expression of FABP4 in colorectal cancer and its clinical significance

Objective:To investigate the relationship between the fatty acid-binding protein 4(FABP4)and colorectal cancer(CRC).Methods:Using an enzyme-linked immunosorbent assay(ELISA),we measured the expression of FABP4 in plasma of50 patients who underwent surgery for CRC from October 2017 to May 2018 and 50 healthy controls.The content of the visceral fat area(VFA)as seen with abdominal computed tomography(CT)scanning was measured by ImageJ software.The expression levels of FABP4,E-cadherin,and Snail proteins in CRC and adjacent tissues were determined by immunohistochemistry.Results:The mean concentration of plasma FABP4 of CRC patients was higher than that of the control group(22.46 vs.9.82 ng/m L;P<0.05).The concentration of plasma FABP4 was related to the tumor,node,metastatis(TNM)stage and lymph node metastasis and was independent of age,body mass index(BMI),tumor size and location,and the degree of differentiation of CRC.The concentration of plasma FABP4 was positively correlated with high VFA and lipoprotein-a(LPA)(P<0.05);but it was not correlated with total cholesterol(TG),total triglyceride(TC),low-density lipoprotein(LDL),high-density lipoprotein(HDL),or apolipoprotein AI(Apo-AI).The expression of FABP4 protein in CRC tissues was positively correlated with the degree of CRC differentiation,tumor stage,and lymph node metastasis.The level of FABP4 protein was negatively correlated with E-cadherin protein(r=-0.3292,P=0.0196)and positively correlated with Snail protein(r=0.5856,P<0.0001).Conclusions:High LPA and VFA were risk factors for increased plasma FABP4 in CRC patients.FABP4 protein was highly expressed in CRC tissues and associated with TNM stage,differentiation,and lymph node metastasis of CRC.The level of FABP4 in CRC tissue was correlated with E-cadherin and Snail expression,suggesting that FABP4 may promote CRC progression related to epithelial-mesenchymal transition(EMT).     

Serum macrophage migration inhibitory factor as a potential biomarker to evaluate therapeutic response in patients with allergic asthma: an exploratory study

Background: Previous studies have shown that macrophage migration inhibitory factor(MIF) is involved in the pathogenesis of asthma. This study aimed to investigate whether serum MIF reflects a therapeutic response in allergic asthma.Methods: We enrolled 30 asthmatic patients with mild-to-moderate exacerbations and 20 healthy controls, analyzing the parameter levels of serum MIF, serum total immunoglobulin E(tIgE), peripheral blood eosinophil percentage(EOS%), and fractional exhaled nitric oxide(FeNO). Lung function indices were used to identify disease severity and therapeutic response.Results: Our study showed that all measured parameters in patients were at higher levels than those of controls. After one week of treatment, most parameter levels decreased significantly except for serum tIgE. Furthermore, we found that serum MIF positively correlated with EOS% as well as FeNO, but negatively correlated with lung function indices. Receiver operator characteristic(ROC) curve analysis indicated that among the parameters, serum MIF exhibited a higher capacity to evaluate therapeutic response. The area under the curve(AUC) of MIF was 0.931, with a sensitivity of 0.967 and a specificity of 0.800.Conclusions: Our results suggested that serum MIF may serve as a potential biomarker for evaluating therapeutic response in allergic asthma with mild-to-moderate exacerbations.     

Exosomes in bladder cancer: novel biomarkers and targets

Exosomes are nanometer-sized vesicles that contain various types of biologically active components, including proteins, nucleic acids, carbohydrates, and lipids, which vary with the type and physiological state of the cell. In recent years,several studies have showed that exosomes can provide new non-invasive diagnostic and prognostic biomarkers in patients affected by cancers, including bladder cancer(BC), and the lipid bilayer membrane structure makes exosomes as promising delivery vehicles for therapeutic applications. Exosomes have the characteristics of high abundance, high stability, tissue specificity, and wide distribution in body fluids, and are secreted as various types by cells in different states, thereby possessing great potential as biomarkers for BC. Herein, we briefly summarize the functions and roles of exosomes in the occurrence and development of BC and the current progress of research on exosomes in BC, while focusing on potential clinical applications of the diagnosis, treatment, and prognosis of BC.     

Development and evaluation of an interactive computer–assisted learning program—a novel approach to teaching gynaecological surgery

Computer Assisted Learning (CAL) is increasingly being recognised as an effective means of teaching and learning. In Gynaecology, the anatomy and surgical steps in vaginal surgery such as vaginal hysterectomy are confusing due to limited access and restricted view of the operative field. The objective of this pilot project was to develop an interactive CAL program on CD–ROM, combining video, illustrations and three–dimensional images to enhance understanding of vaginal hysterectomy in terms of the anatomy and steps of the surgical procedure.
Macromedia Director was used to develop the program. With Director, it is possible to combine text, graphics, animation, video and sound to create interactive material for the web, presentations or CD–ROMS. The CD–ROM takes you through the individual steps of a vaginal hysterectomy combining video clips with voice–over, illustrations and text. The three-dimensional image was included to enhance understanding of the complex relationships between the uterus, bladder and rectum. There is an interactive self–assessment section with multiple–choice questions and an anatomy self–test. The CD–ROM has been evaluated as an educational tool by 12 undergraduate students and 16 trainees in Gynaecology. Most were satisfied with the program. A need for development of further similar educational software has been identified.
The CD–ROM has identified an innovative and useful approach to teaching operative surgery. The results from the evaluation have been positive in terms of the need for similar programs in future.     

CD44v6、nm23-H1在大肠癌中的表达与预后的关系

[目的]探讨CD44v6及nm23-H1蛋白的表达与大肠癌的临床病理意义以及其对大肠癌预后判断的价值.[方法]应用免疫组化技术对52例大肠癌进行上述指标的表达及对比研究.[结果]大肠癌中CD44v6及nm23-H1的阳性表达率分别为65.4％及36.5％.CD44v6与分化程度有关,而nm23-Hl与分化程度无关.二者与肿瘤临床Duke's分期及淋巴结转移密切相关(P<0.05).[结论]CD44v6及nm23-H1的联合检测对判断大肠癌预后有参考价值.     

SEREX技术筛选EID3及其表达的实验研究

[目的]新的大肠癌相关性抗原EID3的基因克隆及其诊断价值研究.[方法]利用大肠癌病人体内血清中所含的对肿瘤抗原产生的特异性抗体筛选睾丸组织cDNA噬菌体表达文库和大肠癌组织cDNA噬菌体表达文库(SEREX),并用RT-PCR技术研究EID3 mRNA在正常组织和大肠癌传代细胞表达.[结果]睾丸组织cDNA噬菌体表达文库筛选得到了可以诱导大肠癌病人抗体免疫应答的新抗原EID3基因(Gen-bank NM_001008394.1).它们定位于染色体19q13.2,EID3含1个外显子.通过RT-PCR分析发现,EID3基因在43例大肠癌传代细胞株中,39例阳性,阳性率为90.7%.在正常组织中,除睾丸组织外不表达或有极低水平转录.[结论]EID3 mRNA表达检测用于诊断大肠癌,可能具有高特异性和高敏感性的特点.EID3蛋白被首次发现在大肠癌病人中能够诱导机体的抗体免疫应答,为一个新的大肠癌相关性抗原分子.其功能可能与抑制细胞的恶性增殖相关,并可进一步研究其用于治疗和诊断大肠癌的可行性.     

Sex-related differences in response to practice on a visual-spatial test and generalization to a related test

93 first graders (mean age 6.5 years) were given a pretest and posttest on half of the items from the Children's Embedded Figures Test. Half of the children were randomly assigned to a training condition and received a brief training procedure on visual-spatial disembedding prior to the administration of the posttest. Children in the control condition received no training. The performance of girls improved significantly more from pretest to posttest than the performance of boys. Boys and girls showed similar beneficial effects of training in addition to the benefit of direct practice. The tendency that was observed for boys to perform higher than girls on the pretest, p less than .10, was not evident on the posttest. Scores on the pretest predicted scores on a different measure of visual-spatial ability only for children in the control group. The results are interpreted in terms of current theories of sex differences in visual-spatial perception.