BackgroundVarious factors can modify the health effects of outdoor air pollution. Prior findings about modifiers are inconsistent, and most of these studies were conducted in developed countries.ObjectivesWe conducted a time-series analysis to examine the modifying effect of season, sex, age, and education on the association between outdoor air pollutants [particulate matter < 10 μm in aerodynamic diameter (PM10), sulfur dioxide, nitrogen dioxide, and ozone] and daily mortality in Shanghai, China, using 4 years of daily data (2001–2004).MethodsUsing a natural spline model to analyze the data, we examined effects of air pollution for the warm season (April–September) and cool season (October–March) separately. For total mortality, we examined the association stratified by sex and age. Stratified analysis by educational attainment was conducted for total, cardiovascular, and respiratory mortality.ResultsOutdoor air pollution was associated with mortality from all causes and from cardiorespiratory diseases in Shanghai. An increase of 10 μg/m3 in a 2-day average concentration of PM10, SO2, NO2, and O3 corresponds to increases in all-cause mortality of 0.25% [95% confidence interval (CI), 0.14–0.37), 0.95% (95% CI, 0.62–1.28), 0.97% (95% CI, 0.66–1.27), and 0.31% (95% CI, 0.04–0.58), respectively. The effects of air pollutants were more evident in the cool season than in the warm season, and females and the elderly were more vulnerable to outdoor air pollution. Effects of air pollution were generally greater in residents with low educational attainment (illiterate or primary school) compared with those with high educational attainment (middle school or above).ConclusionsSeason, sex, age, and education may modify the health effects of outdoor air pollution in Shanghai. These findings provide new information about the effects of modifiers on the relationship between daily mortality and air pollution in developing countries and may have implications for local environmental and social policies.

Cancer-induced immune responses affect tumor progression and therapeutic response. In multiple murine models and clinical datasets, we identified large variations of neutrophils and macrophages, which define “immune subtypes” of triple negative breast cancer (TNBC) including neutrophil-enriched (NES) and macrophage-enriched subtypes (MES). Different tumor-intrinsic pathways and mutual regulation between macrophages/monocytes and neutrophils contribute to the development of dichotomous myeloid compartment. MES contains predominantly macrophages that are CCR2-dependent and exhibit variable responses to immune checkpoint blockade (ICB). NES exhibits systemic and local accumulation of immunosuppressive neutrophils (or granulocytic myeloid-derived suppressor cells (gMDSCs), is resistant to ICB, and contains a minority of macrophages that appear to be unaffected by CCR2 knockout. A MES-to-NES conversion mediated acquired ICB resistance of initially sensitive MES models. Our results demonstrate diverse myeloid cell frequencies, functionality, and potential roles in immunotherapies, and highlight the need to better understand the inter-patient heterogeneity of the myeloid compartment.

Although the number of human infections decreased, human prevalence increased from 4.9% in 1995 to 5.1% in 2004.

Hepatocellular carcinoma (HCC) is characterized by active angiogenesis and metastasis, which account for rapid recurrence and poor survival. There is frequent down-regulation of miR-195 expression in HCC tissues. In this study, the role of miR-195 in HCC angiogenesis and metastasis was investigated with in vitro capillary tube formation and transwell assays, in vivo orthotopic xenograft mouse models, and human HCC specimens. Reduction of miR-195 in HCC tissues was significantly associated with increased angiogenesis, metastasis, and worse recurrence-free survival. Both gain-of-function and loss-of-function studies of in vitro models revealed that miR-195 not only suppressed the ability of HCC cells to promote the migration and capillary tube formation of endothelial cells but also directly repressed the abilities of HCC cells to migrate and invade extracellular matrix gel. Based on mouse models, we found that the induced expression of miR-195 dramatically reduced microvessel densities in xenograft tumors and repressed both intrahepatic and pulmonary metastasis. Subsequent investigations disclosed that miR-195 directly inhibited the expression of the proangiogenic factor vascular endothelial growth factor (VEGF) and the prometastatic factors VAV2 and CDC42. Knockdown of these target molecules of miR-195 phenocopied the effects of miR-195 restoration, whereas overexpression of these targets antagonized the function of miR-195. Furthermore, we revealed that miR-195 down-regulation resulted in enhanced VEGF levels in the tumor microenvironment, which subsequently activated VEGF receptor 2 signaling in endothelial cells and thereby promoted angiogenesis. Additionally, miR-195 down-regulation led to increases in VAV2 and CDC42 expression, which stimulated VAV2/Rac1/CDC42 signaling and lamellipodia formation and thereby facilitated the metastasis of HCC cells. Conclusion: miR-195 deregulation contributes to angiogenesis and metastasis in HCC. The restoration of miR-195 expression may be a promising strategy for HCC therapy. (HEPATOLOGY 2013;58:642-653) G lobally, hepatocellular carcinoma (HCC) is a common and highly lethal malignancy. Active angiogenesis and frequent metastasis are responsible for rapid recurrence and poor survival of HCC. Therefore, identifying molecules that can suppress angiogenesis and metastasis may provide novel targets for HCC therapies.MicroRNAs (miRNAs) constitute a class of endogenous small noncoding RNAs that suppress protein expression by base-pairing with the 3 0 -untranslated

The findings on health effects of ambient fine particles (PM2.5) and coarse particles (PM10-2.5) remain inconsistent. In China, PM2.5 and PM10-2.5 are not the criteria air pollutants, and their monitoring data are scarce. There have been no epidemiological studies of health effects of PM2.5 and PM10-2.5 simultaneously in China. We conducted a time series study to examine the acute effects of PM2.5 and PM10-2.5 on daily mortality in Shanghai, China from Mar. 4, 2004 to Dec. 31, 2005. We used the generalized additive model (GAM) with penalized splines to analyze the mortality, air pollution and covariate data. The average concentrations of PM2.5 and PM10-2.5 were 56.4 microg/m3 and 52.3 microg/m3 in our study period, and PM2.5 constituted around 53.0% of the PM10 mass. Compared with the Global Air Quality Guidelines set by World Health Organization (10 microg/m3 for annual mean) and U.S. National Ambient Air Quality Standards (15 microg/m3 for annual mean), the PM2.5 level in Shanghai was much higher. We found that PM2.5 was associated with the death rates from all causes and from cardiorespiratory diseases in Shanghai. We did not find a significant effect of PM10-2.5 on mortality outcomes. A10 microg/m3 increase in the 2-day moving average (lag01) concentration of PM2.5 corresponded to 0.36% (95% CI 0.11%, 0.61%), 0.41% (95% CI 0.01%, 0.82%) and 0.95% (95% CI 0.16%, 1.73%) increase of total, cardiovascular and respiratory mortality. For PM10-2.5, the effects were attenuated and less precise. Our analyses provide the first statistically significant evidence in China that PM2.5 has an adverse effect on population health and strengthen the rationale for further limiting levels of PM2.5 in outdoor air in Shanghai.