Non-diabetes status after diagnosis of impaired glucose tolerance and risk of long-term death and vascular complications: A post hoc analysis of the Da Qing Diabetes Prevention Outcome Study.

BACKGROUND: The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified. METHODS AND FINDINGS: In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population. CONCLUSIONS: In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.

High Expression Levels of Fascin-1 Protein in Human Gliomas and its Clinical Relevance.

INTRODUCTION: The fascin-1 protein is a cytoskeleton-like protein, which can prompt structural changes in cell membranes and affect the integrity of intercellular relations to promote invasion and metastasis of tumor cells. In this study, we researched the expression of fascin-1 in glioma. MATERIAL AND METHODS: The fascin-1 protein and mRNA were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Then, we analyzed the relationship between the expression of fascin-1 protein and the clinical pathological characteristics of patients with glioma. Finally, the fascin-1 protein expression status and prognosis of glioma patients were investigated. RESULTS: The fascin-1 protein was mainly located in the cytoplasm of cells from glioma. The high expression rate of fascin-1 protein in glioma tissue was higher than that of normal brain tissue. At same time, we found that high fascin-1 protein expression was significantly correlated with World Health Organization (WHO) grading of glioma patients. The results survival analysis suggested high expression of fascin-1 protein in glioma patients with a shorter survival time. Multivariate analysis showed that high expression of fascin-1 protein was an independent predictor of the prognosis of patients with glioma. CONCLUSIONS: High expression of the fascin-1 protein indicates poor prognosis for glioma patients.

MicroRNA-326 sensitizes human glioblastoma cells to curcumin via the SHH/GLI1 signaling pathway.

Glioblastoma multiforme is the most malignant and common brain tumor in adults and is characterized by poor survival and high resistance to chemotherapy and radiotherapy. Among the new chemotherapy drugs, curcumin, a popular dietary supplement, has proven to have a potent anticancer effect on a variety of cancer cell types; however, it remains difficult to achieve a satisfactory therapeutic effect with curcumin using the traditional single-drug treatment. In this study, we found that expression of miR-326, a tumor suppressor microRNA in various tumor types, resulted in a marked increase of curcumin-induced cytotoxicity and apoptosis and a decrease of proliferation and migration in glioma cells. Moreover, we found that combination treatment of miR-326 and curcumin caused significant inhibition of the SHH/GLI1 pathway in glioma cells compared with either treatment alone, independent of p53 status. Furthermore, in vivo, the curcumin-induced increase in miR-326 expression altered the anti-glioma mechanism of this combination treatment, which further reduced tumor volume and prolonged the survival period compared to either treatment alone. Taken together, our data strongly support an important role for miR-326 in enhancing the chemosensitivity of glioma cells to curcumin.

Bioinformatic Profiling Identifies a Glucose-Related Risk Signature for the Malignancy of Glioma and the Survival of Patients.

The aim of this study is to investigate the glucose metabolic status and its prognostic value in glioma. The Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and GSE16011 datasets were used to develop the glucose-related signature. A cohort of 305 glioma samples with whole genome microarray expression data from the Chinese Glioma Genome Atlas database was included for discovery. TCGA and GSE16011 datasets were used for validation. Gene Set Enrichment Analysis (GSEA) and Cytoscape were used to explore the bioinformatic implication. GSEA revealed the biological process associated with the glucose-related signature. Cytoscape visualized the correlation analysis among the genes. We also collected the blood glucose information of patients with gliomas to analyze the association with tumor malignancy and patients' survival. In this study, we identified that glucose-related gene sets could distinguish the clinical and molecular features of gliomas, involved in the malignancy of gliomas. And then, we developed a glucose-related prognostic signature for patients with glioblastoma in the CGGA dataset, validated in other additional public datasets. GSEA illustrated that tumor with higher risk score of glucose-related signature could correlate with cell cycle phase. In addition, blood glucose concentration was associated with the malignancy of glioma and the survival of patients. These results might provide new view for the research of glioma malignancy and individual treatment. Our research provided important resources for future dissection of glucose metabolic role in glioma.

GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment.

BACKGROUND: The aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms. METHODS: The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. CCK-8 assay detected the cell proliferative capability. Apoptotic cell number was measured by flow cytometry. The transwell assay was used to test the cell invasive capability. DNA damage effect was identified by COMET assay and γH2AX expression. RESULTS: Proliferation of tumor cells treated with GANT61 in combination with TMZ was significantly suppressed compared with those treated with either drug used alone. The combination treatment induced a higher rate of apoptosis, DNA damage and reduced the invasive capability of glioma cells. DNA damage repair enzyme MGMT and the Notch1 pathway increased in the cells treated by TMZ treatment. However, GANT61 could abrogated the protein increasing. CONCLUSIONS: GANT61 sensitizes glioma cells to TMZ treatment by enhancing DNA damage effect, decreasing MGMT expression and the Notch1 pathway.

Prevalence and factors associated with occupational burnout among HIV/AIDS healthcare workers in China: a cross-sectional study.

BACKGROUND: Burnout is a psychosomatic syndrome characterized by three dimensions (emotional exhaustion [EE], feelings of depersonalization [DP], and reduced personal accomplishment [PA]). We determined the prevalence of burnout and mental health status between HIV/AIDS healthcare workers and other healthcare workers, and determined the factors associated with burnout of HIV/AIDS healthcare workers. METHODS: All participants were asked to complete a self-administered questionnaire. The participants were recruited from the departments of infectious diseases in four hospitals which treated HIV/AIDS. The questionnaire included demographics, the Maslach Burnout Inventory-General Survey (MBI-GS), the Symptom Checklist 90 (SCL-90), the Eysenck Personality Questionnaire (EPQ), and the Trait Coping Style Questionnaire (TCSQ). RESULTS: A total of 512 questionnaires were distributed; 501 questionnaires were completed and collected (the response rate was 97.9 %). After eliminating nine invalid questionnaires (1.80 %), 264 physicians and nurses caring for HIV/AIDS and 228 physicians and nurses caring for other infectious diseases provided valid responses (98.2 %). The HIV/AIDS healthcare workers' scores on the emotional exhaustion (F = 6.350, p = 0.012) and depersonalization dimensions (F = 8.533, p = 0.004) were significantly higher than other healthcare workers. The HIV/AIDS healthcare workers had higher total scores and positive items on the Symptom Checklist 90 (SCL-90) compared with other healthcare workers. Low job satisfaction, serious somatization, interpersonal sensitivity, poor quality of sleep, high psychoticism scores, and use of negative coping styles were frequently associated with burnout. CONCLUSIONS: Burnout was shown to be highly prevalent in HIV/AIDS healthcare workers, 76.9 % of whom met the accepted criteria for burnout. In addition, compared with other healthcare workers, HIV/AIDS healthcare workers experienced lower levels of psychological health. Interventions should be targeted at reducing the occurrence of burnout and alleviating psychological pressure amongst HIV/AIDS healthcare workers.

Prevalence estimates for primary brain tumors in China: a multi-center cross-sectional study.

BACKGROUND: Although the first leading cause of death in China was malignant neoplasms (mortality, 374.1 per 100,000 person-years), the full impact of primary brain tumors (PBT) on the healthcare system is not completely described because there are a few well documented reports about the epidemiologic features of brain tumors. This study aimed to report a comprehensive assessment on the prevalence of PBT. METHODS: A multicenter cross-sectional study on brain tumor (MCSBT) in China was initiated in five regional centers: Daqing (northeast), Puyang (north of China), Shiyan (center of China), Ma'anshan (center of China) and Shanghai (southeast). Prevalence rate was calculated by counting the number of people living with a PBT between October 1, 2005 and September 30, 2006 and dividing by the total population of the five communities at January 1, 2006. Estimates of prevalence were expressed as percentages and grouped according to gender and to age in fifteen-year categories. Within these strata, the rates were estimated with 95% confidence intervals (CI) using the accurate calculation of CI for Poisson distribution. A chi-square test was used to compare the various frequencies with α < 0.05. Age-standardized prevalence with the direct method was calculated with the ten-year age-specific prevalence and the age distribution of the Chinese population in 2010, obtained from World population prospects: the 2008 revision. RESULTS: We estimated that the overall prevalence of PBT was 24.56 per 100,000 (95%CI, 14.85 to 34.27), and the overall prevalence of PBT in female population (30.57 per 100,000 and its 95%CI ranged from 19.73 to 41.41) was higher than that in male population (18.84 per 100,000 and its 95%CI ranged from 10.33 to 27.35). However, the discrepancy between genders was not statistically significant because the 95%CI overlapped. Of 272 cases of newly diagnosed PBT, the proportion of histological subtypes by age groups, gender was statistically different (χ(2) = 52.6510, P < 0.0001). More than half of all reported tumors (52.57%) were either gliomas or meningiomas. For the youngest (aged from 0 - 19) strata of the population, glioma appeared to occur more than other subtypes, accounting for 55.56% of all of cases. The majority of brain tumors presented in those aged from 20 to 59 years was pituitary adenomas (45.12%) and gliomas (31.10%). Opposed to brain tumors in adults and teenage, gliomas only accounted for 22.22%. Meanwhile, the median ages at diagnosis of the patients with PBT were similar between males and females except for pituitary adenomas (male: 59 years old; female: 45 years old). CONCLUSIONS: Age standardized prevalence of PBT is 22.52 per 100,000 (95%CI, 13.22 to 31.82) for all populations, 17.64 per 100,000 (95%CI, 9.41 to 25.87) for men, and 27.94 per 100,000 (95%CI, 17.58 to 38.30) for women. Age standardization to China's 2010 population yielded an estimated population of 304 954 cases with PBT. Our prevalence estimates provide a conservative basis on which to plan health care services and to develop programmatic strategies for surviving. In the future, it would be helpful to have long-term observed survival rates that would make the assumptions and the resulting imprecision in the current estimates unnecessary.