Coarse particulate matter associated with increased risk of emergency hospital admissions for pneumonia in Hong Kong.

BACKGROUND: Epidemiological research on the effects of coarse particles (PMc, particulate matter between 2.5 and 10 µm in aerodynamic diameter) on respiratory morbidity is sparse and inconclusive. Pneumonia is an inflammatory condition of lung caused by infections, which may be triggered and exacerbated by PMc exposure. AIM: To estimate the effect of PMc on emergency hospital admissions for pneumonia after controlling for PM(2.5) and gaseous pollutants. METHOD: PMc concentrations were estimated by subtracting PM(2.5) from PM(10) measurements in each of the 10 air monitoring stations from January 2011 to December 2012 in Hong Kong and then citywide daily average concentrations of PMc were computed from the 10 stations. Generalised additive Poisson models were used to examine the relationship between PMc and daily emergency hospital admissions for pneumonia, adjusting for PM(2.5) and gaseous pollutants (NO(2), SO(2) and O(3)). Subgroup analyses by gender and age were also performed to identify the most susceptible subpopulations. RESULTS: PMc and PM(2.5) were significantly associated with emergency pneumonia hospitalisations. Every 10 µg/m(3) increment of PMc in the past 4 days (lag0-lag3) was associated with a 3.33% (95% CI 1.54% to 5.15%) increase in emergency hospitalisations for pneumonia. The effect estimates of PMc were robust to the adjustment of PM(2.5), NO(2) or SO(2), but attenuated on the inclusion of O(3) in the model. Women, children and older people might be more vulnerable to PMc exposure. CONCLUSIONS: Short-term PMc exposure is associated with emergency hospitalisations for pneumonia in Hong Kong. Air quality regulation specifically for PMc might be considered.

[Relationship between high incidence of lung cancer among non-smoking women and silica in C1 bituminous coal in Xuanwei, Yunnan Province, China].

OBJECTIVE: To measure the content of silica in C1 bituminous coal and its combustion products in the high-incidence area of lung cancer in Xuanwei, Yunnan Province, China and to investigate the relationship between high incidence of lung cancer among non-smoking women and silica produced naturally in C1 bituminous coal in Xuan Wei. METHODS: The C1 bituminous coal widely used in the high-incidence area of lung cancer in Xuanwei was selected as experiment group, while the C2+1, K7, and M30 bituminous coal that was mined and used in the low-incidence area of lung cancer in Xuanwei for more than 10 years were selected as control group. Fourteen paraffin-embedded cancer tissue samples from the non-smoking women with non-small cell lung cancer who were born in Xuanwei and were at least the 3rd generation of the family living there were collected from the department of pathology, the third affiliated hospital of kunming medical university (tumor hospital of yunnan province). Titrimetric potassium silicofluoride method was used to measure the content of silica in raw coal and its bottom ashes in 20 samples from the experimental group and control group. Scanning electron microscopy (SEM) was used to observe the morphology of silica particles in C1 bituminous coal and its bottom ashes, and scanning electron microscopy coupled with energy dispersive X-ray analyzer (SEM-EDX) was used to analyze the microscopic composition. Transmission electron microscope (TEM) was used to observe the morphology of silica particles in the bottom ashes and coal soot of C1 bituminous coal as well as the lung cancer tissue from the non-smoking women in Xuanwei, and transmission electron microscope coupled with energy dispersive X-ray analyzer (TEM-EDX) was used to analyze the microscopic composition. The silica particles were separated from the coal soot and bottom ashes and characterized by physical method. RESULTS: The silica content in C1 bituminous coal and its bottom ashes was significantly higher than that in C2+1, K7, and M30 bituminous coal (P < 0.05). The bottom ashes of C1 bituminous coal contained a large quantity of silica particles, mostly with microscale sizes. Silica particles were found in the soot of C1 bituminous coal and the lung cancer tissue from non-smoking women in Xuanwei. The silica particles in the bottom ashes were mostly 120 ∼ 500 nm in diameter, had various shapes, and contained such elements as iron, aluminium, calcium, and potassium; the silica particles in the coal soot were mostly nanoscale, ranging from 37 nm to 80 nm in diameter, had various shapes, with some in fibrous form, had non smooth surfaces, and contained such elements as iron, potassium, calcium, aluminium, and sulfur. CONCLUSION: In Xuanwei, the incidence of lung cancer among non-smoking women is high in the area where silica-rich C1 bituminous coal is produced. There are silica particles enriched in both the combustion products (coal soot and bottom ashes) of C1 bituminous coal and the cancer tissue from the non-smoking women with non-small cell lung cancer, with similar morphology and microscopic composition. We hypothesize that the silica particles from combusted C1 bituminous coal in Xuanwei are mixed with indoor air and inhaled along with other suspended particles.

A Systematic Review on Modeling Methods and Influential Factors for Mapping Dengue-Related Risk in Urban Settings.

Dengue fever is an acute mosquito-borne disease that mostly spreads within urban or semi-urban areas in warm climate zones. The dengue-related risk map is one of the most practical tools for executing effective control policies, breaking the transmission chain, and preventing disease outbreaks. Mapping risk at a small scale, such as at an urban level, can demonstrate the spatial heterogeneities in complicated built environments. This review aims to summarize state-of-the-art modeling methods and influential factors in mapping dengue fever risk in urban settings. Data were manually extracted from five major academic search databases following a set of querying and selection criteria, and a total of 28 studies were analyzed. Twenty of the selected papers investigated the spatial pattern of dengue risk by epidemic data, whereas the remaining eight papers developed an entomological risk map as a proxy for potential dengue burden in cities or agglomerated urban regions. The key findings included: (1) Big data sources and emerging data-mining techniques are innovatively employed for detecting hot spots of dengue-related burden in the urban context; (2) Bayesian approaches and machine learning algorithms have become more popular as spatial modeling tools for predicting the distribution of dengue incidence and mosquito presence; (3) Climatic and built environmental variables are the most common factors in making predictions, though the effects of these factors vary with the mosquito species; (4) Socio-economic data may be a better representation of the huge heterogeneity of risk or vulnerability spatial distribution on an urban scale. In conclusion, for spatially assessing dengue-related risk in an urban context, data availability and the purpose for mapping determine the analytical approaches and modeling methods used. To enhance the reliabilities of predictive models, sufficient data about dengue serotyping, socio-economic status, and spatial connectivity may be more important for mapping dengue-related risk in urban settings for future studies.

Childhood Wheeze, Allergic Rhinitis, and Eczema in Hong Kong ISAAC Study from 1995 to 2015.

BACKGROUND: The prevalence of allergic diseases has been increasing in developing areas but has reached a plateau in many developed areas. Regular surveys are imperative to assess the disease burden for the prioritization of resource allocation. OBJECTIVES: We examined the change in the prevalence of wheezing, allergic rhinitis (AR), and eczema in school-aged children with possible associative factors and possible health effects of school air quality. METHODS: This was the third repeated cross-sectional study conducted in 2015-2016 using the International Study of Asthma and Allergies in Childhood (ISAAC) protocol. Our first and second surveys were conducted in 1994-1995 and 2000-2001, respectively. Regarding the third survey, we recruited 3698 children aged 6-7 from 33 local schools in 18 districts. Air quality, temperature, and humidity were also measured. The changes in prevalence, multiple regression, and GLIMMIX procedure were analyzed. RESULTS: From our first survey to our third survey, the increased prevalences for lifetime wheeze, current wheeze, lifetime rhinitis, current rhinitis, current rhinoconjunctivitis, lifetime chronic rash, and current chronic rash were 4.2%, 2.1%, 12.5%, 12.6%, 14.2%, 3.9%, and 4.1%, respectively. Increased prevalence of parental atopy had the strongest association with an increased prevalence of each of these seven health outcomes. There was no significant association between school air pollutant levels and the prevalence of health outcomes. CONCLUSIONS: There was an increase in the prevalence of wheezing, allergic rhinitis, and eczema across the surveys. The most important associated risk factor identified was the increased prevalence of a parental history of atopy.

Methylation of protocadherin 10, a novel tumor suppressor, is associated with poor prognosis in patients with gastric cancer.

BACKGROUND & AIMS: By using methylation-sensitive representational difference analysis, we identified protocadherin 10 (PCDH10), a gene that encodes a protocadherin and is silenced in a tumor-specific manner. We analyzed its epigenetic inactivation, biological effects, and prognostic significance in gastric cancer. METHODS: Methylation status was evaluated by combined bisulfite restriction analysis and bisulfite sequencing. The effects of PCDH10 re-expression were determined in growth, apoptosis, proliferation, and invasion assays. PCDH10 target genes were identified by complementary DNA microarray analysis. RESULTS: PCDH10 was silenced or down-regulated in 94% (16 of 17) of gastric cancer cell lines; expression levels were restored by exposure to demethylating agents. Re-expression of PCDH10 in MKN45 gastric cancer cells reduced colony formation in vitro and tumor growth in mice; it also inhibited cell proliferation (P < .01), induced cell apoptosis (P < .001), and repressed cell invasion (P < .05), up-regulating the pro-apoptosis genes Fas, Caspase 8, Jun, and CDKN1A; the antiproliferation gene FGFR; and the anti-invasion gene HTATIP2. PCDH10 methylation was detected in 82% (85 of 104) of gastric tumors compared with 37% (38 of 104) of paired nontumor tissues (P < .0001). In the latter, PCDH10 methylation was higher in precancerous lesions (27 of 45; 60%) than in chronic gastritis samples (11 of 59; 19%) (P < .0001). After a median follow-up period of 16.8 months, multivariate analysis revealed that patients with PCDH10 methylation in adjacent nontumor areas had a significant decrease in overall survival. Kaplan-Meier survival curves showed that PCDH10 methylation was associated significantly with shortened survival in stage I-III gastric cancer patients. CONCLUSIONS: PCDH10 is a gastric tumor suppressor; its methylation at early stages of gastric carcinogenesis is an independent prognostic factor.

Characteristics and toxicological effects of commuter exposure to black carbon and metal components of fine particles (PM2.5) in Hong Kong.

Epidemiological studies have demonstrated significant associations between traffic-related air pollution and adverse health outcomes. Personal exposure to fine particles (PM2.5) in transport microenvironments and their toxicological properties remain to be investigated. Commuter exposures were investigated in public transport systems (including the buses and Mass Transit Railway (MTR)) along two sampling routes in Hong Kong. Real-time sampling for PM2.5 and black carbon (BC), along with integrated PM2.5 sampling, were performed during the warm and cold season of 2016-2017, respectively. Commuter exposure to BC during 3-hour commuting time exhibited a wider range, from 3.4 to 4.6 µg/m3 on the bus and 5.5 to 8.7 µg/m3 in MTR cabin (p < .05). PM2.5 mass and major chemical constituents (including organic carbon (OC), elemental carbon (EC), and metals) were analyzed. Cytotoxicity, including cellular reactive oxygen species (ROS) production, was determined in addition to acellular ROS generation. PM2.5 treatment promoted the ROS generation in a concentration-dependent manner. Consistent diurnal variations were observed for commuter exposure to BC and PM2.5 components, along with cellular and acellular ROS generation, which marked with two peaks during the morning (08:00-11:00) and evening rush hours (17:30-20:30). Commuter exposures in the MTR system were characterized by higher levels of PM2.5 and elemental components (e.g., Ca, Cr, Fe, Zn, Ba) compared to riding the bus, along with higher cellular and acellular ROS production (p < .01). These metals were attributed to different sources: rail tracks, wheels, brakes, and crustal origin. Weak to moderate associations were shown for the analyzed transition metals with PM2.5-induced cell viability and cellular ROS. Multiple linear regression analysis revealed that Ni, Zn, Mn, Fe, Ti, and Co attributed to cytotoxicity and ROS generation. These findings underscore the importance of commuter exposures and their toxic effects, urging effective mitigating strategies to protect human health.

Single nucleotide polymorphism of rs430397 in the fifth intron of GRP78 gene and clinical relevance of primary hepatocellular carcinoma in Han Chinese: risk and prognosis.

Large number of data showed that allele variants in certain genes are markers for hepatocellular carcinoma (HCC). GRP78 is a stress-associated protein which is a central regulator of endoplasmic reticulum homeostasis due to its multiple functional roles in the folding, maturation and transport of proteins. A case-control study was conducted on 576 HCC patients, and 539 age- and gender-matched healthy subjects to examine whether rs430397 polymorphism in the fifth intron of GRP78 gene is associated with the development and prognosis of HCC. Polymorphism in rs430397 was analyzed by resequencing and TaqMan real-time PCR. Allele A, genotype AA and combined genotypes (AG+AA) displayed significantly increased risk for HCC (OR = 1.48, 95%CI = 1.07-1.79, p = 0.010; OR = 2.25, 95%CI = 1.08-3.38, p = 0.019; and OR = 1.50, 95%CI = 1.09-1.85, p = 0.012, respectively). Genotypes AA and AG were mainly associated with HBV-related HCC (85.8%; p < 0.00001 versus HBV noncarriers with HCC) and cirrhosis-related HCC (90%; p = 0.011 versus noncirrhosis HCC). Patients carrying the AA genotype had a shorter survival time (median 23.0 months in all cases; median 21.0 months in the cases carrying HBsAg). Like HBV and cirrhosis, the rs430397 is an independent prognostic factor influencing the survival of HCC. In conclusion, allele A and genotypes AA and AG of rs430397 may represent high risk and poor prognosis for HCC.

[Expression profile of miR-501-5p in lung adenocarcinoma patients from Xuanwei area].

OBJECTIVE: To investigate the relationship between miR-501-5p expression and the clinicopathological factors in patients with lung adenocarcinoma in Xuanwei area. METHODS: Surgical specimens of lung adenocarcinoma and paired adjacent tissues from 24 patients with lung adenocarcinoma from Xuanwei area were examined for miR-501-5p expression using microRNA microarray technique and qPCR. Chi-square test was used to analyze the association of miR-501-5P expression with the clinicopathological characteristics of the patients. Multiple regression analysis was performed to analyze the association of miR-501-5p expression with the patients' gender, age, tumor stage, and preoperative CEA level. RESULTS: MicroRNA microarray analysis and qPCR validation results revealed significantly upregulated expressions of miR-501-5p in patients with lung adenocarcinoma from Xuanwei area (Plt;0.01). The microarray data showed an up-regulation of miR-501-5p by 3.17 folds in lung adenocarcinoma tissue compared with the adjacent tissue (P=0.22376, FDR=0.071395). Chi-square test indicated that miR-501-5p expression level was associated with the patients' age (f=7.168, P=0.014), TNM stage (f=36.627, P<0.01), and preoperative serum CEA level (f=30.045, Plt;0.01), but not with the patients' gender (f=3.612, P=0.071). Multiple regression analysis revealed that miR-501-5p expression was positively correlated with the patients' age, TNM stage of the tumor, and serum CEA (Plt;0.05). CONCLUSION: miR-501-5p expression is up-regulated in lung adenocarcinoma with significant associations with the patients' age, TNM stages and serum CEA level in patients from Xuanwei area, suggesting its potential role in the tumorigenesis and progression of lung adenocarcinoma in Xuanwei area.

[Species of Iron in Size-resolved Particle Emitted from Xuanwei Coal Combustion and Their Oxidative Potential].

Many reports have claimed that high lung cancer mortality rate in Xuanwei is associated with the residential coal combustion. Considering iron is the main chemical element in the particles emitted from Xuanwei coal combustion, and especially, reactive oxygen species (ROS) could be generated by redox-active transition metals (TM) such as iron (Fe) in particles, therefore, raw coal samples from 4 coal mines in Xuanwei were sampled, and size-resolved particles emitted from the raw coal samples were collected by using of Andersen Five-stage High Volume Sampler. Species of iron in the raw coal sample, size-resolved particles and bottom ashes were analyzed by BCR sequential extraction method (community bureau of reference, BCR). The generation potential of·OH free radicals from coal emission particles in the surrogate lung fluid (SLF) solution was measured by using high pressure liquid chromatography (HPLC). Our results demonstrated that a large fraction of oxidizable Fe could be found in raw coal samples. However, the acid extractable, reducible and oxidizable fractions of Fe in the fly ash particles accounted for a large proportion (46%-78%) in the size-resolved particles after coal combustion. There was difference in levels of·OH free radicals generated from coal emission particles in the SLF for 24 hours among particles with different sizes. The concentration of·OH increased in both fine particles (<1 µm, 1.1-2 µm, 2-3.3 µm) and coarse particles (3.3-7 µm, >7 µm) as the particles size decreased. Linear correlation could be found between the oxidizable fractions of iron and the generation of·OH in particles emitted from coal combustion (R2=0.32).

Characterization of Somatic Mutations in Air Pollution-Related Lung Cancer.

Air pollution has been classified as Group 1 carcinogenic to humans, but the underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China attributed to severe air pollution generated by combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used. Whole genome sequencing revealed a mean of 289 somatic exonic mutations per tumor and the frequent C:G â†’ A:T nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor, respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS, CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers the mutation spectrum of air pollution-related lung cancers, and provides evidence for pollution exposure-genomic mutation relationship at a large scale.