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Subjective cognitive complaints (SCC) might be a meaningful indicator of dementia onset or mild cognitive impairment, and identifying the related factors of SCC could contribute to preventing these diseases. However, the relationship between SCC and lifestyle factors remains largely unproven. The purpose of this study was to examine the association of type of sedentary behavior, physical activity, or their combination with SCC among community-dwelling older adults. In 2016, 6677 community-living elderly were recruited to participate in a survey investigating cognition, physical activity, and sedentary behavior. In total, 5328 participants responded to the questionnaire (79.8% valid response rate). SCC was assessed using the National Functional Survey Questionnaire (Kihon checklist). The relationships between SCC and physical activity, sedentary behavior (reading books or newspapers, and television viewing), or combined physical activity and sedentary behavior were examined via multiple logistic regression analysis. The analysis revealed that moderate-to-vigorous physical activity (≥150 min/week) was significantly related with a lower risk of SCC (odds ratio [OR] = 0.85; 95% confidence interval [CI] = 0.74-0.97), and that reading behavior showed a dose-response relationship with SCC (OR for 10-20 min/day = 0.63; 95% CI = 0.53-0.75; OR for 20-30 min/day = 0.59; 95% CI = 0.49-0.71; OR for ≥30 min/day = 0.47; 95% CI = 0.39-0.57). In addition, among those reporting high physical activity and ≥30 min/day for reading time, the OR for SCC was 0.40 (95% CI = 0.32-0.50) compared with the combined group reporting lower physical activity and non-readers. The present study shows that increased physical activity and reading time may be related to a reduced risk for SCC among community-dwelling older adults.

Definitive chemoradiotherapy (CRT) is a less invasive therapy for esophageal squamous cell carcinoma (ESCC). Five-year survival rate of locally advanced ESCC patients by definitive CRT were 37%. We previously reported that tumor-specific cytotoxic T-lymphocyte (CTL) activation signatures were preferentially found in long-term survivors. However, it is unknown whether the CTL activation is actually driven by CRT. We compared gene expression profiles among pre- and post-treatment biopsy specimens of 30 ESCC patients and 121 pre-treatment ESCC biopsy specimens. In the complete response (CR) cases, 999 overexpressed genes including at least 234 tumor-specific CTL-activation associated genes such as IFNG, PRF1, and GZMB, were found in post-treatment biopsy specimens. Clustering analysis using expression profiles of these 234 genes allowed us to distinguish the immune-activated cases, designating them as I-type, from other cases. However, despite the better CR rate in the I-type, overall survival was not significantly better in both these 30 cases and another 121 cases. Further comparative study identified a series of epithelial to mesenchymal transition-related genes overexpressed in the early relapse cases. Importantly, the clinical outcome of CDH2-negative cases in the I-type was significantly better than that of the CDH2-positive cases in the I-type. Furthermore, NK cells, which were activated by neutrophils-producing S100A8/S100A9, and CTLs were suggested to cooperatively enhance the effect of CRT in the CDH2-negative I-type. These results suggested that CTL gene activation may provide a prognostic advantage in ESCCs with epithelial characteristics.

Introduction: This study aimed to determine current levels of physical activity and sedentary behavior in middle school students on the basis of grade, sex, student attitudes toward physical education, and residence location., Methods: In 2013, a cross-sectional study of 1793 students aged 12 to 15 years was conducted across eight middle schools in Beijing, China. Four schools were selected from an urban district and another four schools were from a suburban district. Physical activity and sedentary behavior data were collected using the commonly used school-based Chinese version of the China Health and Nutrition Survey., Results: The mean age of sampled students was 13.3 ± 1.0 years; 51.5% were boys. Approximately 76.6% of students reported having three 45-minute physical education classes every week. A total of 35.6% students spent ≥ 1 h/day performing moderate to vigorous physical activity (MVPA) during school, and 34.9% spent ≥ 1 h/day in MVPA outside school time. Approximately half (49.7%) of the students engaged in reading, writing, or drawing for ≥ 2 h/day, and 42.9% reported screen time for ≥ 2 h/day. Although boys spent more time engaged in physical activity than girls did, they also spent more time exhibiting sedentary behavior. Each 10-unit increase in attitudes toward physical education was associated with an increased odds of 1.15 (95%CI: 1.09-1.20) for spending more than 1 h/day on MVPA. Students in suburban schools reported engaging in physical activity less when compared with those in urban schools., Conclusion: The majority of our students did not meet the current physical activity recommendations, and about half of the students spent excessive time engaging in sedentary behaviors. Findings from this study highlight a positive association between student attitudes toward physical education and physical activity. Studies are needed to further explore the role of student attitudes toward physical education in promoting physical activity among Chinese students.

An on-chip multi-imaging flow cytometry system has been developed to obtain morphometric parameters of cell clusters such as cell number, perimeter, total cross-sectional area, number of nuclei and size of clusters as "imaging biomarkers", with simultaneous acquisition and analysis of both bright-field (BF) and fluorescent (FL) images at 200 frames per second (fps); by using this system, we examined the effectiveness of using imaging biomarkers for the identification of clustered circulating tumor cells (CTCs). Sample blood of rats in which a prostate cancer cell line (MAT-LyLu) had been pre-implanted was applied to a microchannel on a disposable microchip after staining the nuclei using fluorescent dye for their visualization, and the acquired images were measured and compared with those of healthy rats. In terms of the results, clustered cells having (1) cell area larger than 200 µm2 and (2) nucleus area larger than 90 µm2 were specifically observed in cancer cell-implanted blood, but were not observed in healthy rats. In addition, (3) clusters having more than 3 nuclei were specific for cancer-implanted blood and (4) a ratio between the actual perimeter and the perimeter calculated from the obtained area, which reflects a shape distorted from ideal roundness, of less than 0.90 was specific for all clusters having more than 3 nuclei and was also specific for cancer-implanted blood. The collected clusters larger than 300 µm2 were examined by quantitative gene copy number assay, and were identified as being CTCs. These results indicate the usefulness of the imaging biomarkers for characterizing clusters, and all of the four examined imaging biomarkers-cluster area, nuclei area, nuclei number, and ratio of perimeter-can identify clustered CTCs in blood with the same level of preciseness using multi-imaging cytometry.

Background: Despite strong recommendations to involve family social support in hypertension control, few questionnaires have been designed to measure family support in Chinese patients. The Chinese Family Support Scale is a self-rated questionnaire that assesses family support over a 6-month period., Methods: A total of 282 patients with hypertension participated in this study and 136 of them completed the questionnaire twice within an interval of two to three weeks. Exploratory factor analysis was conducted to assess the structural validity of the scale. Concurrent validity was determined by measuring the correlation between the Chinese Family Support Scale, and Hospital Anxiety and Depression Scale using the Sperman's Correlation Coefficient. Cronbach's alpha and intraclass correlation coefficients were employed to evaluate the internal and test-retest reliability of the scale., Results: Exploratory factor analysis revealed a three-factor solution accounting for 62% of the total variance. The three underlying sub-scale dimensions were kinship, nuclear family, and social resources. Significant correlation (r=-0.266; p<0.01) was found between the depression subscales of the Hospital Anxiety and Depression Scale and the extent of support perceived by the patients as measured by the Chinese Family Support Scale. The Chinese Family Support Scale had an acceptable internal consistency (Cronbach's alpha = 0.84) and test-retest reliability (intraclass correlation coefficient = 0.82)., Conclusion: The study provides preliminary evidence that the 12-item Chinese Family Support Scale is acceptable, valid and reliable for measuring the perceived family support in hypertension patients. It is a promising tool which can be easily incorporated into epidemiological surveys.

Background: The biological basis for cancer of unknown primary (CUP) at the molecular level remains largely unknown, with no evidence of whether a common biological entity exists. Here, we assessed the possibility of identifying a common diagnostic biomarker for CUP using a microarray gene expression analysis., Methods: Tumor mRNA samples from 60 patients with CUP were analyzed using the Affymetrix U133A Plus 2.0 GeneChip and were normalized by asinh (hyperbolic arc sine) transformation to construct a mean gene-expression profile specific to CUP. A gene-expression profile specific to non-CUP group was constructed using publicly available raw microarray datasets. The t-tests were performed to compare the CUP with non-CUP groups and the top 59 CUP specific genes with the highest fold change were selected (p-value<0.001)., Results: Among the 44 genes that were up-regulated in the CUP group, 6 genes for ribosomal proteins were identified. Two of these genes (RPS7 and RPL11) are known to be involved in the Mdm2-p53 pathway. We also identified several genes related to metastasis and apoptosis, suggesting a biological attribute of CUP., Conclusions: The protein products of the up-regulated and down-regulated genes identified in this study may be clinically useful as unique biomarkers for CUP.

Non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations attains a meaningful response to EGFR-tyrosine kinase inhibitors (TKIs). However, acquired resistance to EGFR-TKIs could affect long-term outcome in almost all patients. To identify the potential mechanisms of resistance, we established cell lines resistant to EGFR-TKIs from the human lung cancer cell lines PC9 and11-18, which harbored activating EGFR mutations. One erlotinib-resistant cell line from PC9 and two erlotinib-resistant cell lines and two gefitinib-resistant cell lines from 11-18 were independently established. Almost complete loss of mutant delE746-A750 EGFR gene was observed in the erlotinib-resistant cells isolated from PC9, and partial loss of the mutant L858R EGFR gene copy was specifically observed in the erlotinib- and gefitinib-resistant cells from 11-18. However, constitutive activation of EGFR downstream signaling, PI3K/Akt, was observed even after loss of the mutated EGFR gene in all resistant cell lines even in the presence of the drug. In the erlotinib-resistant cells from PC9, constitutive PI3K/Akt activation was effectively inhibited by lapatinib (a dual TKI of EGFR and HER2) or BIBW2992 (pan-TKI of EGFR family proteins). Furthermore, erlotinib with either HER2 or HER3 knockdown by their cognate siRNAs also inhibited PI3K/Akt activation. Transfection of activating mutant EGFR complementary DNA restored drug sensitivity in the erlotinib-resistant cell line. Our study indicates that loss of addiction to mutant EGFR resulted in gain of addiction to both HER2/HER3 and PI3K/Akt signaling to acquire EGFR-TKI resistance.

SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly posttranslational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand-glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.

Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1) is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 up-regulated genes in a highly metastatic gastric cancer cell line (58As1) than their parental low metastatic counterpart (HSC-58). The highly metastatic cell lines showed decreased expression of E-cadherin, together with enhanced expression of vimentin and Snail. This decreased expression of E-cadherin was restored by Snail knockdown in highly metastatic cell lines. We next established stable NDRG1 knockdown cell lines (As1/Sic50 and As1/Sic54) from the highly metastatic cell line, and both of these cell lines showed enhanced expression of E-cadherin and decreased expression of vimentin and Snail. And also, E-cadherin promoter-driven luciferase activity was found to be increased by NDRG1 knockdown in the highly metastatic cell line. NDRG1 knockdown in gastric cancer cell showed suppressed invasion of cancer cells into surround tissues, suppressed metastasis to the peritoneum and decreased ascites accumulation in mice with significantly improved survival rates. This is the first study to demonstrate that NDRG1 plays its pivotal role in the malignant progression of gastric cancer through epithelial mesenchymal transition.