BACKGROUND:Xuanwei and Fuyuan are rural counties, located in the late Permian coal poly area of eastern Yunnan and western Guizhou, where lung cancer mortality rates are among the highest in the China, with similarity for both men and women, younger age at diagnosis and death, and higher in rural areas than in urban areas. In this paper, long-term follow-up of lung cancer cases in local peasants was conducted to observe their survival prognosis and its influencing factors.METHODS:Data of patients diagnosed with lung cancer from January 2005 to June 2011, who had lived in Xuanwei and Fuyuan counties for many years, were collected from 20 hospitals at the local provincial, municipal and county levels. To estimate survival outcomes, individuals were followed up until the end of 2021. The 5-year, 10-year and 15-year survival rates were estimated using the Kaplan-Meier method. Survival differences were examined with Kaplan-Meier curves and Cox proportional hazards models.RESULTS:A total of 3,017 cases were effectively followed up (2,537 peasants and 480 non-peasants). The median age at diagnosis was 57 years, and the median follow-up time was 122 months. During the follow-up period, 2,493 cases (82.6%) died. The distribution of cases by clinical stage was as follows: stage I (3.7%), stage II (6.7%), stage III (15.8%), stage IV (21.1%) and unknown stage (52.7%). Treatment at the provincial, municipal and county-level hospitals accounted for 32.5%, 22.2% and 45.3%, respectively, and surgical treatment was performed in 23.3% of cases. The median survival time was 15.4 months (95%CI: 13.9-16.1), and the 5-year, 10-year and 15-year overall survival rates were 19.5% (95%CI: 18.0%-21.1%), 7.7% (95%CI: 6.5%-8.8%) and 2.0% (95%CI: 0.8%-3.9%), respectively. Peasants with lung cancer had a lower median age at diagnosis, higher proportion residing in remote rural areas, and higher use of bituminous coal as a household fuel. They also have a lower proportion of early-stage cases, treatment at provincial or municipal hospitals, and surgical treatment, leading to poorer survival outcomes (HR=1.57). Even when considering factors such as gender, age, residential location, clinical stage at diagnosis, histological type, hospital level of service, and surgical intervention, peasants still exhibit a survival disadvantage. Multivariable Cox model analysis comparing peasants and non-peasants reveals that surgical intervention, tumor-node-metastasis (TNM) stage, and hospital level of service are common factors influencing survival prognosis, while the use of bituminous coal as a household fuel, hospital level of service and adenocarcinoma (compared to squamous cell carcinoma) are independent prognostic factors for lung cancer survival among peasants.CONCLUSIONS:The lower lung cancer survival rate among peasants is associated with their lower socioeconomic status, lower proportion of early-stage diagnoses, lower proportion of surgical interventions, and treatment at provincial-level hospitals. Furthermore, the impact of other factors such as high-risk exposure to bituminous coal pollution on survival prognosis requires further investigation.

目的:开展新生儿群体宫内生长等级分类评价,获得新生儿宫内生长水平的客观证据.方法:以《2015年深圳单胎儿、双胎儿出生体重、身长、头围、胸围、顶臀长百分位曲线》为评价参考标准,对中国11市11家妇幼保健院2017-2020年出生的412 755例单胎儿和双胎儿进行宫内生长等级分类评价.结果:获得中国11市395 583例单胎儿、17 172例双胎儿下等、中下等、中等、中上等、上等、小于胎龄儿(SGA)、适于胎龄儿(AGA)、大于胎龄儿(LGA)、营养不良儿、肥胖儿人数和构成比数据.单胎儿出生体重水平从低到高排位:海口、桂林、柳州、广州、泉州、深圳、成都、重庆、长沙、宁波、连云港.双胎儿出生体重水平从低到高排位:柳州、泉州、桂林、海口、广州、成都、重庆、深圳、长沙、宁波、连云港.验证了海口、桂林、柳州、广州、泉州、深圳、重庆、成都、长沙9市合计单胎儿、双胎儿出生体重水平与《2015年深圳单胎儿、双胎儿出生体重曲线》接近;验证了宁波市和连云港市合计单胎儿、双胎儿出生体重水平明显高于《2015年深圳单胎儿、双胎儿出生体重曲线》水平.结论:获得中国11市新生儿宫内生长水平及其排位的客观数据.《2015年深圳单胎儿、双胎儿出生体重曲线》可作为11市新生儿宫内生长评价的参考标准.

OBJECTIVES:To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups.METHODS:The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages.RESULTS:A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups.CONCLUSIONS:The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.

目的 研制胎龄24～42周单胎新生儿出生体重曲线,并探讨其地区差异特征.方法 在中国11市(海口、广州、深圳、柳州、桂林、泉州、重庆、成都、长沙、宁波、连云港)选择年分娩量7000例以上的11家妇幼保健院,纳入其2017年1月1日至2020年12月31日分娩的全部活产单胎新生儿进行出生体重曲线研制.结果 纳入了11市合计93720例胎龄24～42周单胎新生儿进行研究.建立了中国11市合计及各市单胎儿出生体重3rd～97th百分位数参考值,并绘制了出生体重百分位曲线图.深圳市和泉州市单胎儿出生体重曲线水平与中国11市合计单胎儿水平基本相同;海口市、广州市、桂林市、柳州市单胎儿出生体重曲线水平略低于中国11市合计单胎儿水平;重庆市、成都市、长沙市单胎儿出生体重曲线水平略高于中国11市合计单胎儿水平;宁波市和连云港市单胎儿出生体重曲线高于中国11市合计单胎儿水平.中国11市合计单胎儿出生体重曲线与中国协作网2011～2014年单胎儿出生体重曲线非常接近.结论 制定了中国11市合计及各市单胎新生儿出生体重3rd～97th百分位数参考值,可作为该区域新生儿宫内生长评价的参考标准.部分地区新生儿宫内生长水平与全国水平有差异.

OBJECTIVES:To develop the birth weight curve of twin neonates with a gestational age of 25-40 weeks, and to investigate the regional differences of the birth weight curve.METHODS:A total of 11 maternal and child health care hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Liuzhou, Guilin, Quanzhou, Shenzhen, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live twin neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves.RESULTS:A total of 17 256 twin neonates with a gestational age of 25-40 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities in China were established, and the birth weight percentile curves were drawn. The birth weight curve level of twin neonates in Liuzhou was lower than the average level of the 11 cities; the birth weight curve level of twin neonates in Ningbo was higher than the average level of the 11 cities; the birth weight curve level of twin neonates in Lianyungang was obviously higher than the average level of the 11 cities; the birth weight curve level of twin neonates in other 8 cities was almost the same as the average level of the 11 cities.CONCLUSIONS:The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of twin neonates in the region. The level of intrauterine growth of twin neonates in some cities is different from the average level of the 11 cities of China.

OBJECTIVES:To develop the birth weight curve of singleton neonates with a gestational age of 24-42 weeks, and to investigate the regional differences of the birth weight curve. METHODS:A total of 11 maternal and child health hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Shenzhen, Liuzhou, Guilin, Quanzhou, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live singleton neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves. RESULTS:A total of 93 720 singleton neonates with a gestational age of 24-42 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of singleton neonates for the total of the 11 cities and for each of the 11 cities were established, and the birth weight percentile curves were drawn. The birth weight curve level of singleton neonates in Shenzhen and Quanzhou was almost the same as the average level of the 11 cities; the birth weight curve level of singleton neonates in Haikou, Guangzhou, Guilin, and Liuzhou was slightly lower than the average level of the 11 cities; the birth weight curve level of singleton neonates in Chongqing, Chengdu, and Changsha was slightly higher than the average level of the 11 cities; the birth weight curve level of singleton neonates in Ningbo and Lianyungang was higher than the average level of the 11 cities. The average birth weight curve level of singleton neonates in the 11 cities were very close to that of China Neonatal Cooperation Network in 2011-2014. CONCLUSIONS:The reference values of the 3rd-97th percentiles of birth weight of singleton neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of singleton neonates in the region. The level of intrauterine growth of neonates in some cities is different from the national level.

[目的]分析云南省富源县肺癌死亡的行政村级空间分布及其与不同类型煤矿的关系.[方法]恶性肿瘤死亡数据来源于2010-2019年当地户籍居民死因监测系统,并用省、市、县级医院住院病例诊断信息补充、校正,对肺癌死亡特征进行描述与分析.应用GeoDa 1.14软件进行空间变化和空间聚类分析,并结合煤矿床地质分布进行肺癌死亡空间分析.[结果]富源县2010-2019年肺癌死亡6828例,中位死亡年龄65岁,肺癌粗死亡率84.1/10万.男、女性世界人口标化死亡率分别为112.4/10万和74.0/10万,0～74岁累积死亡率分别为12.83％和8.37％.各乡镇死亡差异较大,北部地区肺癌世界人口标化死亡率高于南部.基于161个行政村的全局空间自相关分析结果显示,全局Moran's Ⅰ指数为0.505,其中女性大于男性(0.568 vs 0.431).LISA、EB、Gi*等三种空间聚类分析显示,富源县存在着2个与烟煤亚型矿床分布相关的肺癌高死亡率空间聚集群,即东北部狭长条索状气肥煤小聚集群和中部以1/3焦煤与焦煤矿床交叉区域为中心、横跨5个乡镇的大聚集群.[结论]富源县肺癌发病死亡具有明显的空间聚集性,较高的肺癌死亡率与煤亚型矿床的地质分布和长期室内生活燃煤污染暴露有关.使用聚集区的煤作为生活燃料具有较高肺癌发病风险,并促进肺癌死亡低龄化.

Outdoor air pollution is a growing public health concern, particularly in urban settings. However, there are limited epidemiological data on outdoor air pollution in rural areas with substantial levels of air pollution attributed to solid fuel burning for household cooking and heating. Xuanwei and Fuyuan are rural counties in China where the domestic combustion of locally sourced bituminous (“smoky”) coal has been associated with the highest lung cancer rates in China. We previously assessed indoor and personal air pollution exposures in this area; however, the influence of indoor coal combustion and household ventilation on outdoor air pollution has not been assessed. Therefore, we measured outdoor fine particulate matter (PM2.5), species of polycyclic aromatic hydrocarbons (PAHs) including naphthalene (NAP) and the known carcinogen benzo(a)pyrene (BaP), sulfur dioxide (SO2), and nitrogen dioxide (NO2) over two consecutive 24-h sampling periods in 29 villages. Just over half of the villages were revisited two to nine months after the initial sampling period to repeat all measurements. The overall geometric mean (GM) of outdoor PM2.5, BaP, NAP, and NO2 were 45.3 µg/m3, 9.7 ng/m3, 707.7 ng/m3, and 91.5 µg/m3, respectively. Using linear mixed effects models, we found that burning smoky coal was associated with higher outdoor BaP concentrations [GM ratio (GMR) = 2.79] and lower outdoor SO2 detection rates (GMR = 0.43), compared to areas burning smokeless coal. Areas with predominantly ventilated stoves (> 50% of stoves) had higher outdoor BaP (GMR = 1.49) compared to areas with fewer ventilated stoves. These results show that outdoor air pollution in a rural region of China was associated with the type of coal used for cooking and heating indoors and the presence of stove ventilation. Our findings suggest that efforts of household stove improvement to reduce indoor air pollution have resulted in higher outdoor air pollution levels. Further reducing adverse health effects in rural villages from household coal combustion will require the use of cleaner fuel types.

We previously reported that bacterial diversity in sputum samples from never-smoking women in rural China varied by lung cancer status and household air pollution (HAP) exposure type. Here, we expand on our associations between environmental exposures and respiratory tract microbiota with an additional 90 never-smoking women from Xuanwei, China. DNA from sputum samples of cases ( n = 45) and controls ( n = 45) was extracted using a multistep enzymatic and physical lysis, followed by a standardized clean up. V1–V2 regions of 16S rRNA genes were Polymerase chain reaction (PCR) amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. In our population of never-smokers, increased risk of lung cancer was associated with lower alpha diversity compared to higher alpha diversity (Shannon: OR high = 1.00 [reference], OR medium = 3.84 [1.02–14.48], OR low = 3.78 [1.03–13.82]; observed species: OR high = 1.00 [reference], OR medium = 2.37 [0.67–8.48], OR low = 2.01 [0.58–6.97]; Phylogenetic Diversity (PD) whole tree: OR high = 1.00 [reference], OR medium = 3.04 [0.85–10.92], OR low = 2.53 [0.72–8.96]), as well as a decreased relative abundance of Fusobacteria (OR high = 1.00 [reference], OR medium = 1.24 [0.42–3.66], OR low = 2.01 [0.63–6.44], p trend = 0.03). Increasing alpha diversity was associated with smoky coal use compared to clean fuel use among all subjects (observed species, P = 0.001; PD whole tree, P = 0.006; Shannon, P = 0.0002), as well as cases (observed species, P = 0.02; PD whole tree, P = 0.03; Shannon, P = 0.03) and controls (observed species, P = 0.01; PD whole tree, P = 0.05; Shannon, P = 0.002). Increased diversity was also associated with presence of livestock (observed species, P = 0.02; PD whole tree, P = 0.02; Shannon, P = 0.03) in the home for cases. Our study is the first to report that decreased microbial diversity is associated with risk of lung cancer. Larger studies are necessary to elucidate the direct and indirect effects attributed to the disease-specific, HAP-specific, and animal-specific associations. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

Coal types vary around the world because of geochemical differences in their source deposits; however, the influence of coal emissions from different deposits on human health remains unexplored. To address this issue, we conducted the first study of the relationship between coal use from various deposits and lung cancer risk in Xuanwei and Fuyuan, counties in China where lung cancer rates are among the highest in the world among female never‐smokers due to use of bituminous (“smoky”) coal for heating and cooking. We conducted a population‐based case–control study of 1031 lung cancer cases and 493 controls among never‐smoking women in Xuanwei and Fuyuan. Logistic regression models were used to estimate associations between coal use from various deposits across the lifecourse and lung cancer risk. There was substantial heterogeneity in risks by coal deposit ( p = 7.8E‐05). Compared to non‐smoky coal users, risks by smoky coal deposit ranged from OR = 7.49 (95% CI: 3.43–16.38) to OR = 33.40 (95% CI: 13.07–85.34). Further, women born into homes that used smoky coal and subsequently changed to non‐smoky coal had a higher risk (OR = 10.83 (95% CI: 4.61–25.46)) than women born into homes that used non‐smoky coal and changed to smoky coal (OR = 4.74 (95% CI: 2.03–11.04, p difference = 0.04)). Our study demonstrates that various sources of coal have considerably different impact on lung cancer in this population and suggests that early‐life exposure to carcinogenic emissions may exert substantial influence on health risks later in life. These factors should be considered when evaluating the health risks posed by exposure to coal combustion emissions.

BACKGROUND:Lung cancer rates among women in rural Xuanwei and Fuyuan counties in eastern Yunnan province, China, are among the highest in the world, even though almost all women are non-smokers, and they tend to develop lung cancer at a younger age than other locations by roughly 5 yr-10 yr. This study investigated the survival of lung cancer patients among female never-smokers.METHODS:The female never-smokers, who had lived for many years in Xuanwei and Fuyuan counties, with lung cancer newly-diagnosed between July 2006 to March 2010, were followed up through the end of 2016. Age-standardized relative survival for all cases was calculated using local life table. The Kaplan-Meier method and Log-rank test were used to analyze the relationship between the variables and the prognosis in univariate analysis. Cox regression analysis was employed in the multivariate analysis.RESULTS:Among 1,250 total subjects, 1,075 died and the remaining 175 were censored during the follow-up, with a median follow-up period of 69 months (95%CI: 61.9-76.0). Overall, the mean age was (54.8 ±10.9) yr, with variable clinical stages: 3.5% of cases were stage I, 8.7% stage II, 20.7% stage III, 29.7% stage IV, and 37.4% stage unknown. The 645 patients(51.6%) with cyto-histological diagnosis contains 303 with Squamous cell carcinoma, and 231 with adenocarcinoma, 24 with small cell, 43 with other specified type and 39 with unknown histological type. Only 215 (17.2%) patients received surgery, 487 (39.0%) were treated without surgery, and 548 (43.8%) did not receive any specific anticancer therapy. The 5-year observed survival rate and age-standardized relative survival were 8.9% (95%CI: 7.0-10.6), and 10.1% (95%CI: 3.7-20.5) respectively, with a median survival of 13.2 months. The 5-year survival rates were 41.1% for stage I, 22.4% for stage II, 5.3% for stage III, 1.3% for stage IV, 11.2% for missing stage, 17.9% for adenocarcinoma, and 5.6% for squamous cell carcinoma respectively. Surgery significantly improved 5-year survival rate compared with non-surgery (34.8% vs 3.2%, P<0.001). The patients with non-treatment, aged 65 years and older, living in rural areas and farmer with low socioeconomic status had poorer survival, whereas the patients treated in provincial hospitals and chest X-ray screening had better survival. Cox multivariate analysis further showed that stage of tumor-node-metastasis (TNM), treatment status, hospital-level, and X-ray screening were factors correlated with survival.CONCLUSIONS:Patients with lung cancer among female never-smokers in Xuanwei and Fuyuan experience poorer survival, because they are less likely to be diagnosed at early stage, as well as less likely to receive surgery and comprehensive treatment. Furthermore low socioeconomic status and poor health security are also responsible for the low survival.

We previously reported that bacterial diversity in sputum samples from never-smoking women in rural China varied by lung cancer status and household air pollution (HAP) exposure type. Here, we expand on our associations between environmental exposures and respiratory tract microbiota with an additional 90 never-smoking women from Xuanwei, China. DNA from sputum samples of cases (n = 45) and controls (n = 45) was extracted using a multistep enzymatic and physical lysis, followed by a standardized clean up. V1-V2 regions of 16S rRNA genes were Polymerase chain reaction (PCR) amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. In our population of never-smokers, increased risk of lung cancer was associated with lower alpha diversity compared to higher alpha diversity (Shannon: ORhigh = 1.00 [reference], ORmedium = 3.84 [1.02-14.48], ORlow = 3.78 [1.03-13.82]; observed species: ORhigh = 1.00 [reference], ORmedium = 2.37 [0.67-8.48], ORlow = 2.01 [0.58-6.97]; Phylogenetic Diversity (PD) whole tree: ORhigh = 1.00 [reference], ORmedium = 3.04 [0.85-10.92], ORlow = 2.53 [0.72-8.96]), as well as a decreased relative abundance of Fusobacteria (ORhigh = 1.00 [reference], ORmedium = 1.24 [0.42-3.66], ORlow = 2.01 [0.63-6.44], ptrend = 0.03). Increasing alpha diversity was associated with smoky coal use compared to clean fuel use among all subjects (observed species, P = 0.001; PD whole tree, P = 0.006; Shannon, P = 0.0002), as well as cases (observed species, P = 0.02; PD whole tree, P = 0.03; Shannon, P = 0.03) and controls (observed species, P = 0.01; PD whole tree, P = 0.05; Shannon, P = 0.002). Increased diversity was also associated with presence of livestock (observed species, P = 0.02; PD whole tree, P = 0.02; Shannon, P = 0.03) in the home for cases. Our study is the first to report that decreased microbial diversity is associated with risk of lung cancer. Larger studies are necessary to elucidate the direct and indirect effects attributed to the disease-specific, HAP-specific, and animal-specific associations. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

The study aim was to investigate whether household bituminous ("smoky") coal use and personal exposure to combustion emissions were associated with immunologic/inflammatory marker levels. A cross-sectional study of healthy never-smoking women from rural Xuanwei and Fuyuan, China was conducted, which included 80 smoky coal and 14 anthracite ("smokeless") coal users. Personal exposure to fine particulate matter (PM2.5) and benzo[a]pyrene (BaP) was assessed using portable devices, while 67 circulating plasma immunologic/inflammatory markers were measured using multiplex bead-based assays. Multivariable linear regression models were employed to estimate associations between smoky coal versus smokeless coal use, indoor air pollutants, and immunologic/inflammatory markers. Six markers were altered among smoky coal users compared to smokeless coal, including significantly decreased interferon-inducible T-cell alpha chemoattractant (CXCL11/I-TAC), and increased serum amyloid P component (SAP). CXCL11/I-TAC was previously found to be reduced in workers exposed to high levels of diesel engine exhaust, which exhibits similar constituents as coal combustion emissions. Further, there was evidence that elevated PM2.5 and BaP exposure was associated with significantly diminished levels of the serum amyloid A (SAA); however, the false discovery rates (FDRs) were >0.2 after accounting for multiple comparisons. Inflammatory processes may thus mediate the carcinogenic effects attributed to smoky coal emissions.

Through the occupational hazard control effect of Nan yu mine in Taiyuan, the investigation, inspection and examination methods of occupational health scene were confirmed for qualitative and quantitative evaluation. The total layout of the mine, personal protective facilities, emergency rescue, health auxiliary room, occupational health management are in line with national standards, the existing occupational risk factors in the production process to determine are dust, free silica, noise, hand-vibration, carbon monoxide, carbon dioxide, nitrogen dioxide, sulfur dioxide, ammonia, hydrogen sulfide, manganese and its compounds, microclimate, power frequency electric field, but parts of the dust and noise concentration (or intensity) have exceeded. The mine occupational hazards control measures are feasible and effective, but some post still need to strengthen governance.

Background: Lung cancer rates among never-smoking women in Xuanwei and Fuyuan in China are among the highest in the world and have been attributed to the domestic use of smoky (bituminous) coal for heating and cooking. However, the key components of coal that drive lung cancer risk have not been identified. Objectives: We aimed to investigate the relationship between lifelong exposure to the constituents of smoky coal (and other fuel types) and lung cancer. Methods: Using a population-based case–control study of lung cancer among 1,015 never-smoking female cases and 485 controls, we examined the association between exposure to 43 household air pollutants and lung cancer. Pollutant predictions were derived from a comprehensive exposure assessment study, which included methylated polycyclic aromatic hydrocarbons (PAHs), which have never been directly evaluated in an epidemiological study of any cancer. Hierarchical clustering and penalized regression were applied in order to address high colinearity in exposure variables. Results: The strongest association with lung cancer was for a cluster of 25 PAHs [odds ratio (OR): 2.21; 95% confidence interval (CI): 1.67, 2.87 per 1 standard deviation (SD) change], within which 5-methylchrysene (5-MC), a mutagenic and carcinogenic PAH, had the highest individual observed OR (5.42; 95% CI: 0.94, 27.5). A positive association with nitrogen dioxide (NO2) was also observed (OR: 2.06; 95% CI: 1.19, 3.49). By contrast, neither benzo(a)pyrene (BaP) nor fine particulate matter with aerodynamic diameter ≤2.5μm (PM2.5) were associated with lung cancer in the multipollutant models. Conclusions: To our knowledge, this is the first study to comprehensively evaluate the association between lung cancer and household air pollution (HAP) constituents estimated over the entire life course. Given the global ubiquity of coal use domestically for indoor cooking and heating and commercially for electric power generation, our study suggests that more extensive monitoring of coal combustion products, including methylated PAHs, may be warranted to more accurately assess health risks and develop prevention strategies from this exposure. https://doi.org/10.1289/EHP4913

本文利用具有线粒体定位功能的双光子荧光探针Mito-H2O2,实现对生物体中H2O2的高灵敏检测.在单光子和双光子模式下分别对探针和荧光团进行了检测,发现在弱碱性条件下,H2O2能够与探针硼酸酯发生亲核取代反应,得到荧光团Mito-green(neutral form),随即在弱碱性环境下去质子化形成Mito-green(anion form),通过增强分子内电荷转移(ICT)发出强的绿色荧光.三苯基膦基团能很好地通过细胞膜,定位于线粒体内膜上.实验结果表明,探针与H2O2反应后,Mito-H2O2最大发射峰的相对发射强度在60 min内增加了12倍(540 nm),最大双光子活性截面为20 GM(810 nm).该探针检出限低至412 nmol/L,并且选择性高、细胞毒性低、光稳定性好.实验还考察了脂多糖(LPS)诱导神经免疫过程中小鼠大脑炎症过程中H2O2浓度的变化,发现LPS能够有效刺激小鼠大脑中H2O2的增加,加入抗炎药物NS-398能有效缓解小鼠大脑神经免疫.

To explore the influence of fuel source used for home heating and cooking on biomarkers of potential genomic instability, we analyzed biological samples obtained from a cross-sectional study of 104 female never-smokers enrolled from 30 villages in Xuanwei and Fuyuan in Yunnan Province, a rural region with a high incidence of lung cancer in China. Study subjects who used primarily smoky (i.e., bituminous) coal (n=80), smokeless coal (i.e., anthracite) (n=14) and wood (n=10) were analyzed. Personal 24-h air PM2.5 and polycyclic aromatic hydrocarbon concentrations were measured over two consecutive days in each household. DNA was extracted from peripheral white blood cells. We assayed molecular biomarkers of potential genomic instability including the Alu copy number to albumin gene (ALB) ratio (Alu/ALB), 5.8S ribosomal DNA to ALB ratio (5.8S rDNA/ALB) and 18S ribosomal DNA to ALB ratio (18S rDNA/ALB), which were weakly to highly correlated with each other. Multiple linear regression was performed to analyze the association between fuel type and these biomarkers, adjusted for age, as well as the influence of benzo[a]pyrene (BaP) and PM2.5 concentration. There was a significant difference (p = 0.041) in levels of 18S rDNA/ALB among the three exposure groups [mean (standard deviation [sd]) = 1.30 (0.42), 1.58 (0.72), and 1.65 (0.62) among smoky, smokeless coal and wood users, respectively]. There were substantial differences in personal PM2.5 exposure among smoky coal, smokeless coal, and wood users [mean (sd) =184 (127), 227 (318), and 433 (284) µg/m3, respectively, p = 0.0004]. PM2.5 exposure was significantly and positively associated with 18S rDNA/ALB (p = 0.001). Further, after adjustment for PM2.5, the association between fuel type and 18S rDNA/ALB became non-significant (p = 0.24). Similar positive associations were observed between PM2.5 and 5.8S rDNA/ALB (p=0.009) and Alu/ALB (p=0.0003). There were no associations identified between BaP and these biomarkers after adjustment for PM2.5. Our findings suggest that exposure to PM2.5, which has been associated with increased risks of lung cancer and cardiovascular disease, may alter potential molecular markers of genomic instability. Additional studies are needed to confirm these findings and further understand the role of these biomarkers in predicting human health effects. Citation Format: Wei Hu, Richard M. Cawthon, George Downward, Boris Reiss, Jihua Li, Jun He, Jun Xu, Wei Jie Seow, Bryan A. Bassig, Jason Y. Wong, Dean Hosgood, Lutzen Portengen, Nathaniel Rothman, Roel Vermeulen, Qing Lan. Molecular biomarkers and indoor household air pollution in a rural area of China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3239.

Households in Xuanwei and Fuyuan, China, possess hazardous levels of fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) from coal combustion. Previous studies found that increased exposure to PM2.5 and benzo[a]pyrene (BaP; a PAH) were associated with decreased mitochondrial DNA copy number (mtDNAcn), a marker of oxidative stress. We further evaluated these associations in a cross-sectional study of 148 healthy non-smoking women from Xuanwei and Fuyuan. Personal exposure to PM2.5 and BaP was measured using portable devices. MtDNAcn was measured using qPCR amplification of leukocyte DNA that was collected after air measurements. Linear regression models were used to estimate the associations between personal exposure to PM2.5 and BaP, and mtDNAcn adjusted for age, body mass index (BMI) and fuel type. We found inverse associations between exposure to PM2.5 and BaP, and mtDNAcn. Each incremental log-μg/m3 increase in PM2.5 was associated with a significant decrease in mtDNAcn of -10.3 copies per cell [95% confidence interval (95% CI): -18.6, -2.0; P = 0.02]. Additionally, each log-ng/m3 increase in BaP was associated with a significant decrease in mtDNAcn of -5.4 copies per cell (95% CI: -9.9, -0.8, P = 0.02). Age, BMI, fuel type and coal mine type were not significantly associated with mtDNAcn. Exposure to PM2.5 and BaP may alter mitochondrial dynamics in non-smoking Chinese women. MtDNAcn may be a potential mediator of indoor air pollution on chronic disease development.

Abstract Xuanwei and Fuyuan are rural counties in China that have the highest lung cancer rates in the country among non-smoking women. This alarming public health burden has been attributed to the combustion of smoky (bituminous) coal for heating and cooking, which can produce carcinogenic emissions such as polycyclic aromatic hydrocarbons (PAHs). Previous studies found that green leafy vegetables could absorb PAHs through air and direct soil contamination. Further, oral ingestion of PAHs was found be to associated with pulmonary adenoma development in animal feeding studies. Therefore, we investigated the associations between lung cancer risk and dietary intake of specific green leafy vegetables and other foods in non-smoking women of this farming region. We conducted a hospital-based case-control study of 1,074 female lung cancer patients and 977 frequency-matched controls from Xuanwei and Fuyuan, China in 2006-2013. Dietary intake was self-reported on questionnaires and categorized as never, several times/year, several times/month, several times/week, and every day. Unconditional logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) of lung cancer in relation to intake of specific green leafy vegetables (i.e. lettuce, cabbage, fennel, spinach, hollow vegetables), corn, buckwheat, carrots, tomatoes, dried and fresh chili, pickled vegetables, bean curd, mushrooms, and preserved meats. Models were adjusted for age, county, first-degree relative with lung cancer, passive smoke exposure, education, lifetime smoky coal tonnage, respiratory disease history, time spent indoors, and menopausal status. Separate models were fitted for each dietary factor. We found that increased consumption of several green leafy vegetables was associated with increased risk of lung cancer. Eating hollow vegetables every day was associated with 2.50 (95% CI: 1.18, 5.27) times the odds of lung cancer compared to never. Similarly, eating lettuce (OR=2.13, 95% CI: 1.41, 3.21) and cabbage (OR=1.82, 95% CI: 1.21, 2.69) every day was associated with increased risks compared to several times a year or less. Conversely, eating bean curd (OR=0.54, 95% CI: 0.40, 0.72) several times a week was associated with decreased risk compared to several times a year or less; while eating buckwheat (OR=0.59, 95% CI: 0.40, 0.89) several times a week was associated with decreased risk compared to never. No significant associations were found for fennel, spinach, and other foods. Our findings suggest that increased consumption of a variety of green leafy vegetables may be related to elevated lung cancer risk in non-smoking women from Xuanwei and Fuyuan, China, independent of other risk factors. The increased risk may be due to environmental contamination of crops from coal combustion. Conversely, frequent consumption of bean curd and buckwheat was found to be protective. Citation Format: Jason Y. Wong, Bryan A. Bassig, Wei Hu, Jinming Zhang, Wei Jie Seow, Neil E. Caporaso, Bu-tian Ji, Robert S. Chapman, George S. Downward, Jihua Li, Jun He, Kaiyun Yang, Yunchao Huang, Roel Vermeulen, Nathaniel Rothman, Qing Lan. Dietary intake and risk of lung cancer in non-smoking women: a hospital-based case-control study in Xuanwei and Fuyuan, China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5315. doi:10.1158/1538-7445.AM2017-5315