可吸入大气颗粒物污染与居民每日死亡关系的Meta分析

目的综合分析国内外可吸入大气颗粒物（PM10）短期暴露与人群死亡关系的流行病学资料,以获取大气PM10污染与居民死亡的暴露-反应关系。方法在计算机联机检索文献和手工检索的基础上,对近十年来发表的相关研究文献采用meta分析的方法进行综合评价,并检验、校正可能存在的发表偏倚,从而准确、定量地确定PM10污染与居民死亡的暴露-反应关系。结果建立了居民短期接触大气PM10污染的暴露一反应关系,即在未考虑发表偏倚的情况下,大气中PM10每增加1130μg／m3,居民死亡的相对危险度增加3．87％（95％CI：2．84％～5．02％）,在校正了发表偏倚后大气中PM10每增加100μg／m3,死亡的相对危险度增加下降为1．41％（95％CI：0．30％-2．43％）,与考虑偏倚前相比下降了63．6％。结论本研究建立的暴露-反应关系较早注意到发表偏倚的影响,具有一定的代表性与科学性,可用于大气颗粒物暴露健康危险度评价工作参考,为制定相关环境决策提供科学依据。     

The Effect of Fine and Coarse Particulate Air Pollution on Mortality: A National Analysis

Background

Although many studies have examined the effects of air pollution on mortality, data limitations have resulted in fewer studies of both particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM_2.5; fine particles) and of coarse particles (particles with an aerodynamic diameter > 2.5 and < 10 μm; PM coarse). We conducted a national, multicity time-series study of the acute effect of PM_2.5 and PM coarse on the increased risk of death for all causes, cardiovascular disease (CVD), myocardial infarction (MI), stroke, and respiratory mortality for the years 1999–2005.

Method

We applied a city- and season-specific Poisson regression in 112 U.S. cities to examine the association of mean (day of death and previous day) PM_2.5 and PM coarse with daily deaths. We combined the city-specific estimates using a random effects approach, in total, by season and by region.

Results

We found a 0.98% increase [95% confidence interval (CI), 0.75–1.22] in total mortality, a 0.85% increase (95% CI, 0.46–1.24) in CVD, a 1.18% increase (95% CI, 0.48–1.89) in MI, a 1.78% increase (95% CI, 0.96–2.62) in stroke, and a 1.68% increase (95% CI, 1.04–2.33) in respiratory deaths for a 10-μg/m³ increase in 2-day averaged PM_2.5. The effects were higher in spring. For PM coarse, we found significant but smaller increases for all causes analyzed.

Conclusions

We conclude that our analysis showed an increased risk of mortality for all and specific causes associated with PM_2.5, and the risks are higher than what was previously observed for PM₁₀. In addition, coarse particles are also associated with more deaths.     

Exposure to Concentrated Coarse Air Pollution Particles Causes Mild Cardiopulmonary Effects in Healthy Young Adults

Background

There is ample epidemiologic and toxicologic evidence that exposure to fine particulate matter (PM) air pollution [aerodynamic diameter ≤ 2.5 μm (PM_2.5)], which derives primarily from combustion processes, can result in increased mortality and morbidity. There is less certainty as to the contribution of coarse PM (PM_2.5–10), which derives from crustal materials and from mechanical processes, to mortality and morbidity.

Objective

To determine whether coarse PM causes cardiopulmonary effects, we exposed 14 healthy young volunteers to coarse concentrated ambient particles (CAPs) and filtered air. Coarse PM concentration averaged 89.0 μg/m³ (range, 23.7–159.6 μg/m³). Volunteers were exposed to coarse CAPs and filtered air for 2 hr while they underwent intermittent exercise in a single-blind, crossover study. We measured pulmonary, cardiac, and hematologic end points before exposure, immediately after exposure, and again 20 hr after exposure.

Results

Compared with filtered air exposure, coarse CAP exposure produced a small increase in polymorphonuclear neutrophils in the bronchoalveolar lavage fluid 20 hr postexposure, indicating mild pulmonary inflammation. We observed no changes in pulmonary function. Blood tissue plasminogen activator, which is involved in fibrinolysis, was decreased 20 hr after exposure. The standard deviation of normal-to-normal intervals (SDNN), a measure of overall heart rate variability, also decreased 20 hr after exposure to CAPs.

Conclusions

Coarse CAP exposure produces a mild physiologic response in healthy young volunteers approximately 20 hr postexposure. These changes are similar in scope and magnitude to changes we and others have previously reported for volunteers exposed to fine CAPs, suggesting that both size fractions are comparable at inducing cardiopulmonary changes in acute exposure settings.     

Diesel exhaust particles induce endothelial dysfunction in apoE-/- mice

BACKGROUND: Particulate air pollution can aggravate cardiovascular disease by mechanisms suggested to involve translocation of particles to the bloodstream and impairment of endothelial function, possibly dependent on present atherosclerosis. AIM: We investigated the effects of exposure to diesel exhaust particles (DEP) in vivo and ex vivo on vasomotor functions in aorta from apoE(-/-) mice with slight atherosclerosis and from normal apoE(+/+) mice. METHODS: DEP 0, 0.5 or 5 mg/kg bodyweight in saline was administered i.p. The mice were sacrificed 1 h later and aorta ring segments were mounted on wire myographs. Segments from unexposed mice were also incubated ex vivo with 0, 10 and 100 microg DEP/ml before measurement of vasomotor functions. RESULTS: Exposure to 0.5 mg/kg DEP in vivo caused a decrease in the endothelium-dependent acetylcholine elicited vasorelaxation in apoE(-/-) mice, whereas the response was enhanced in apoE(+/+) mice. No significant change was observed after administration of 5 mg/kg DEP. In vivo DEP exposure did not affect constriction induced by K(+) or phenylephrine. In vitro exposure to 100 microg DEP/ml enhanced acetylcholine-induced relaxation and attenuated phenylephrine-induced constriction. Vasodilation induced by sodium nitroprusside was not affected by any DEP exposure. CONCLUSION: Exposure to DEP has acute effect on vascular functions. Endothelial dysfunction possibly due to decreased NO production as suggested by decreased acetylcholine-induced vasorelaxation and unchanged sodium nitroprusside response can be induced by DEP in vivo only in vessels of mice with some atherosclerosis.     

Bilateral vagotomy or atropine pre-treatment reduces experimental diesel-soot induced lung inflammation

To investigate the role of the vagus nerve in acute inflammatory and cardiorespiratory responses to diesel particulate (DP) in the rat airway, we measured changes in respiration, blood pressure and neutrophils in lungs of urethane anesthetized Wistar rats 6-h post-instillation of DP (500 microg) and studied the effect of mid-cervical vagotomy or atropine (1 mg kg(-1)) pre-treatment. In conscious rats, we investigated DP, with and without atropine pre-treatment. DP increased neutrophil level in BAL (bronchoalveolar lavage) fluid from intact anesthetized rats to 2.5+/-0.7x10(6) cells (n=8), compared with saline instillation (0.3+/-0.1x10(6), n=7; P<0.05). Vagotomy reduced DP neutrophilia to 0.8+/-0.2x10(6) cells (n=8; P<0.05 vs. intact); atropine reduced DP-induced neutrophilia to 0.3+/-0.2x10(6) (n=4; P<0.05). In conscious rats, DP neutrophilia of 8.5+/-1.8x10(6), n=4, was reduced by pre-treatment with atropine to 2.2+/-1.2x10(6) cells, n=3. Hyperventilation occurred 6 h after DP in anesthetized rats with intact vagi, but not in bilaterally vagotomized or atropine pre-treated animals and was abolished by vagotomy (P<0.05, paired test). There were no significant differences in the other variables (mean blood pressure, heart rate and heart rate variability) measured before and 360 min after DP. In conclusion, DP activates a pro-inflammatory vago-vagal reflex which is reduced by atropine. Muscarinic ACh receptors in the rat lung are involved in DP-induced neutrophilia, and hence muscarinic antagonists may reduce airway and/or cardiovascular inflammation evoked by inhaled atmospheric DP in susceptible individuals.     

Dietary coral calcium and zeolite protects bone in a mouse model for postmenopausal bone loss

In patients diagnosed with osteoporosis, calcium is lost from bones making them weaker and easily susceptible to fractures. Supplementation of calcium is highly recommended for such conditions. However, the source of calcium plays an important role in the amount of calcium that is assimilated into bone. We hypothesize that naturally occurring coral calcium and zeolite may prevent ovariectomy-induced bone loss. We have measured bone loss in ovariectomized mice supplemented with coral calcium and Zeolite. Female C57BL/6 mice were either sham-operated or ovariectomized and fed diets containing coral calcium or zeolite for 6 months. Serum was analyzed for bone biochemical markers and cytokines. Bones were analyzed using dual x-ray absorbtiometry, peripheral quantitative computed tomography, and micro–computed tomography densitometry. In the distal femoral metaphysis, total bone and cortical bone mass was restored and the endocortical surface was significantly decreased in coral calcium and zeolite fed ovariectomized (OVX) mice. Trabecular number and the ratio of bone volume to total volume was higher in OVX mice after coral calcium and zeolite feeding, while trabecular separation decreased in the different treatment OVX groups. Coral calcium protected bone to a lesser extent in the proximal tibia and lumbar vertebrae. Overall, coral calcium and zeolite may protect postmenopausal bone loss.     

Do causal concentration–response functions exist? A critical review of associational and causal relations between fine particulate matter and mortality

Concentration–response (C–R) functions relating concentrations of pollutants in ambient air to mortality risks or other adverse health effects provide the basis for many public health risk assessments, benefits estimates for clean air regulations, and recommendations for revisions to existing air quality standards. The assumption that C–R functions relating levels of exposure and levels of response estimated from historical data usefully predict how future changes in concentrations would change risks has seldom been carefully tested. This paper critically reviews literature on C–R functions for fine particulate matter (PM2.5) and mortality risks. We find that most of them describe historical associations rather than valid causal models for predicting effects of interventions that change concentrations. The few papers that explicitly attempt to model causality rely on unverified modeling assumptions, casting doubt on their predictions about effects of interventions. A large literature on modern causal inference algorithms for observational data has been little used in C–R modeling. Applying these methods to publicly available data from Boston and the South Coast Air Quality Management District around Los Angeles shows that C–R functions estimated for one do not hold for the other. Changes in month-specific PM2.5 concentrations from one year to the next do not help to predict corresponding changes in average elderly mortality rates in either location. Thus, the assumption that estimated C–R relations predict effects of pollution-reducing interventions may not be true. Better causal modeling methods are needed to better predict how reducing air pollution would affect public health.     

Risk factors for the presence of residual disease in women after partial mastectomy for invasive breast cancer: A single institution experience

BackgroundWe hypothesize that in addition to specimen margin widths other clinical variables may help predict the presence of residual disease in the lumpectomy bed.MethodsPatients with Stage I-III invasive breast cancer (BC) who underwent partial mastectomy (PM) and re-excision from July 2010–June 2015 were retrospectively reviewed. Bivariate analyses were conducted using two-sample t-tests for continuous variables and Fisher's Exact tests for categorical variables. A multivariate logistic regression was then performed on significant bivariate analyses variables.Resultsne-hundred and eighty-four patients were included in our analysis; 47% had residual disease on re-excision, while 53% had no residual disease. Tumor and nodal stage, operation type, type of disease present at margin, and number of positive margins were significantly associated with residual disease. On multivariate logistic regression, DCIS alone at the margin (p = 0.02), operation type (PM with cavity margins) (p = 0.003), and number of positive margins (3 or more) (p < 0.001) remained predictive of residual disease at re-excision.ConclusionBased on a more comprehensive review of the initial pathology, there are additional factors that can help predict the likelihood of finding residual disease and help guide the surgeon in the decision for re-excision.     

p38MAPK基因对PM2.5染毒HK-2细胞部分癌基因和凋亡相关基因表达的影响

目的：探讨p38MAPK基因对PM_2.5染毒人肾上皮细胞（HK-2）部分癌基因和凋亡相关基因表达的影响。方法：根据GenBank提供的p38MAPK mRNA序列,设计合成干扰序列,将重组慢病毒载体转染HK-2细胞,构建p38MAPK基因沉默细胞株。分别采用实时荧光定量PCR （qPCR）和Western blot法检测p38MAPK mRNA和蛋白的表达水平鉴定沉默效果。用50 μg/mL的PM_2.5混悬液分别染毒正常HK-2细胞和p38MAPK基因沉默细胞24 h,利用荧光定量PCR和Western blot检测癌基因c-myc,c-fos、p53和凋亡相关基因Caspase-8、Caspase-9、Bcl-2的mRNA和蛋白的相对表达水平。结果：qPCR和Western blot检测结果显示,与正常HK-2细胞比较,p38MAPK基因沉默细胞中p38MAPK mRNA的表达下降了58.50%,p38MAPK蛋白表达水平下降了51.33%（P<0.01）。PM_2.5混悬液对HK-2细胞和p38MAPK基因沉默HK-2细胞染毒后,qPCR检测结果显示,与正常HK-2细胞未染毒组比较,正常HK-2细胞PM_2.5染毒组中c-myc、c-fos、Caspase-8和Casepase-9基因表达分别升高39.89%、15.12%、19.47%和15.45%,p53和Bcl-2基因表达分别下降21.54%和31.77%,差异均具有统计学意义（P<0.05）;与正常HK-2细胞PM_2.5染毒组比较,p38MAPK基因沉默HK-2细胞PM_2.5染毒组中c-myc、c-fos、p53、Caspase-8和Caspase-9 mRNA表达分别下降了84.55%、63.55%、34.49%、37.19%和54.97%,差异均具有统计学意义（P<0.05）。Western blot检测结果显示,与正常HK-2细胞未染毒组比较,正常HK-2细胞PM_2.5染毒组中的c-myc和Caspase-8蛋白表达增加,Bcl-2蛋白表达减少;与正常HK-2细胞PM_2.5染毒组比较,p38MAPK基因沉默HK-2细胞PM_2.5染毒组中的c-myc、Caspase-8和Bcl-2蛋白表达减少（均为P<0.05）。结论：成功构建了p38MAPK基因沉默细胞株,PM_2.5可引起HK-2细胞癌基因和凋亡相关基因表达水平升高,p38MAPK基因可能参与PM_2.5对HK-2细胞的毒性作用过程。