Organophosphorus Flame Retardant TPP-Induced Human Corneal Epithelial Cell Apoptosis through Caspase-Dependent Mitochondrial Pathway.

A widely used organophosphate flame retardant (OPFR), triphenyl phosphate (TPP), is frequently detected in various environmental media and humans. However, there is little known on the human corneal epithelium of health risk when exposed to TPP. In this study, human normal corneal epithelial cells (HCECs) were used to investigate the cell viability, morphology, apoptosis, and mitochondrial membrane potential after they were exposed to TPP, as well as their underlying molecular mechanisms. We found that TPP decreased cell viability in a concentration-dependent manner, with a half maximal inhibitory concentration (IC50) of 220 µM. Furthermore, TPP significantly induced HCEC apoptosis, decreased mitochondrial membrane potential in a dose-dependent manner, and changed the mRNA levels of the apoptosis biomarker genes (Cyt c, Caspase-9, Caspase-3, Bcl-2, and Bax). The results showed that TPP induced cytotoxicity in HCECs, eventually leading to apoptosis and changes in mitochondrial membrane potential. In addition, the caspase-dependent mitochondrial pathways may be involved in TPP-induced HCEC apoptosis. This study provides a reference for the human corneal toxicity of TPP, indicating that the risks of OPFR to human health cannot be ignored.

Effects of TCPP and TCEP exposure on human corneal epithelial cells: Oxidative damage, cell cycle arrest, and pyroptosis.

Tris(2-chloroisopropyl) phosphate (TCPP) and Tris(2-chloroethyl) phosphate (TCEP) are the widely used organophosphorus flame retardants indoors and easily accessible to the eyes as the common adhesive components of dust and particle matter, however, hardly any evidence has demonstrated their corneal toxicity. In this study, the adverse effects of TCPP, TCEP, and TCPP + TCEP exposure on human corneal epithelial cells (HCECs) were investigated. The cell viability and morphology, intracellular reactive oxygen species (ROS), cell cycle, and the expressions of cell cycle and pyroptosis-related genes were assessed to explain the underlying mechanisms. Compared to individual exposure, co-exposure to TCPP20+TCEP20 showed higher cytotoxicity with a sharp decrease of >30% in viability and more serious oxidative damage by increasing ROS production to 110.92% compared to the control group. Furthermore, the cell cycle arrested at the S phase (36.20%) was observed after combined treatment, evidenced by the upregulation of cyclin D1, CDK2, CDK4, CDK6, p21, and p27. Interestingly, pyroptosis-related genes GSDMD, Caspase-1, NLRP3, IL-1ß, IL-18, NLRP1, and NLRC4 expressions were promoted with cell swelling and glowing morphology. Oxidative stress and cell cycle arrest probably acted as a key role in TCPP20+TCEP20-induced cytotoxicity and pyroptosis in HCECs. Our results suggested that TCPP20+TCEP20 co-exposure induced severer corneal damage, further illustrating its significance in estimating indoor health hazards to humans.

Indoor air pollution and human ocular diseases: Associated contaminants and underlying pathological mechanisms.

People spend a long time indoors, especially young children. The risk of indoor pollution on human health is one of the current hotspots in environmental and public health. The human ocular surface is highly susceptible to indoor environment quality. Epidemiological data have linked human ophthalmological disorders with exposure to indoor pollution. In this review, we summarized the adverse impacts of indoor pollution on the human ocular surface. Several studies demonstrated that indoor contaminants including particulate matter, volatile/semi-volatile organic compounds, heavy metals, and fuel combustion and cigarette smoke exposure were associated with the incidence of human dry eye, conjunctivitis, glaucoma, cataracts, age-related macular degeneration, and keratitis. In addition, toxicological investigations revealed that indoor pollution-induced induced chronic inflammation, oxidative damage, and disruption of tight junctions are the main underlying pathological mechanisms for ocular surface diseases. Taken together, this review may expand the understanding of pollution-induced eye disorder and highlight the importance of reducing associated contaminants to decrease their detrimental effects on human eyes.

Organophosphorus Flame Retardant TCPP Induces Cellular Senescence in Normal Human Skin Keratinocytes: Implication for Skin Aging.

Tris (1-chloro-2-propyl) phosphate (TCPP) is one of the most frequently detected organophosphorus flames in the environment. Continuous daily exposure to TCPP may harm human skin. However, little is known about the adverse effects of TCPP on human skin. In this study, we first evaluated the detrimental effects and tried to uncover the underlying mechanisms of TCPP on human skin keratinocytes (HaCaT) after 24 h exposure. We found that TCPP caused a concentration-dependent decrease in HaCaT cell viability after exposure to 1.56-400 µg/mL for 24 h, with an IC50 of 275 µg/mL. TCPP also promoted the generation of intracellular reactive oxygen species (ROS) and triggered DNA damage, evidenced by an increase of phosphorylated histone H2A.X (γH2A.X) in the nucleus. Furthermore, the cell cycle was arrested at the G1 phase at 100 µg/mL by upregulation of the mRNA expression of p53 and p21 and downregulation of cyclin D1 and CDK4 expression. Additionally, both the senescence-associated-ß-galactosidase activity and related proinflammatory cytokine IL-1ß and IL-6 were elevated, indicating that TCPP exposure caused cellular senescence may be through the p53-dependent DNA damage signal pathway in HaCaT cells. Taken together, our data suggest that flame-retardant exposure may be a key precipitating factor for human skin aging.

Mechanical behavior and reinforcement mechanism of nanoparticle cluster fillers in dental resin composites: Simulation and experimental study.

OBJECTIVES: In dental resin composites (DRCs), the structure of fillers has a great impact on the mechanical behavior. The purpose of this study is to gain an in-depth understanding of the reinforcement mechanism and mechanical behavior of DRCs with nanoparticle clusters (NCs) fillers, thereby providing a guidance for the optimal design of filler structures for DRCs. METHODS: This work pioneers the use of discrete element method (DEM) simulations combined with experiments to study the mechanical behavior and reinforcement mechanism of DRCs with NCs fillers. RESULTS: The uniaxial compressive strength (UCS) of NCs-reinforced DRCs have an improvement of 9.58 % and 15.02 % in comparison with nanoparticles (NPs) and microparticles (MPs), respectively, because of the ability of NCs to deflect cracks and absorb stress through gradual fracturing. By using NCs and NPs as co-fillers, the internal defects of DRCs can be reduced, resulting in a further improvement of UCS of DRCs by 6.21 %. Furthermore, the mechanical properties of DRCs can be effectively improved by increasing the strength of NCs or reducing the size of NCs. SIGNIFICANCE: This study deepens the understanding of relationship between filler structure and mechanical behavior in DRCs at the mesoscale and provides an avenue for the application of DEM simulations in composite materials.

Effects of Nickel at Environmentally Relevant Concentrations on Human Corneal Epithelial Cells: Oxidative Damage and Cellular Apoptosis.

Nickel (Ni) is ubiquitous in the environment and evidence has suggested that Ni can cause ocular surface inflammation, especially in fine particulate matter and personal products. Continuous daily exposure to Ni-containing dust may adversely impact the human cornea, whereas the underlying mechanism of this phenomenon remains not fully understood. Here, human corneal epithelial cells (HCEC) were employed to analyze the toxicity of Ni via detections of cell morphology, cell viability, reactive oxygen species production, cell apoptosis rate, and apoptotic gene expression levels after exposure for 24 h to uncover the damage of Ni to the cornea. A concentration-dependent inhibition of HCECs' viability and growth was observed. In particular, Ni at 100 µM significantly decreased cell viability to 76%, and many cells displayed an abnormal shape and even induced oxidative damage of HCEC by increasing ROS to 1.2 times, and further led to higher apoptosis (24%), evidenced by up-regulation of apoptotic genes Caspase-8, Caspase-9, NF-κB, IL-1ß, and Caspase-3, posing a risk of dry eye. Our study suggested that Ni induces apoptosis of HCEC through oxidative damage. Therefore, Ni pollution should be comprehensively considered in health risks or toxic effects on the ocular surface.

Spray-drying-assisted fabrication of CaF2/SiO2 nanoclusters for dental restorative composites.

OBJECTIVE: The objective of this study is to develop novel CaF2/SiO2 nanoclusters (NCs) fillers, which can endow the dental resin composites (DRCs) with excellent mechanical properties, stable and sustained fluoride ion release, and good antibacterial activity. METHODS: The CaF2/SiO2 NCs were efficiently fabricated by assembling CaF2/SiO2 nanoparticles (NPs) as building blocks with a spray-drying technology. CaF2/SiO2 NCs with different SiO2 coating amounts (20 wt%, 50 wt% and 80 wt%) were incorporated into the DRCs at the filler content of 55 wt% for the measurement of mechanical properties including flexural strength, flexural modulus, compressive strength, and hardness. The effect of the filling amount of CaF2/50SiO2 NCs (50 represents 50 wt% SiO2 coating amount) in the DRCs was investigated, while CaF2/50SiO2 NPs were adopted as comparison group. The fluoride ion release and antibacterial activity of the DRCs with the optimal mechanical performances were evaluated. Furthermore, the statistical analyses were performed for mechanical properties. RESULTS: Spherical CaF2/50SiO2 NCs with an average size of 2.4 µm were obtained at the feed rate of 7.4 mL/min and the CaF2/50SiO2 NPs solid content of 2 wt% in the suspension. The optimum comprehensive performances of the DRCs can be achieved by filling 55 wt% CaF2/50SiO2 NCs. Compared with CaF2/50SiO2 NPs, the filling amount of CaF2/50SiO2 NCs was increased by 5 wt% (50-55 wt%), and under the same filling amount of 50 wt%, the flexural strength, flexural modulus, compressive strength, and hardness of the DRCs containing CaF2/50SiO2 NCs were improved by 9.8%, 17.7%, 7.5% and 69.8%, respectively. Furthermore, the DRCs filled with 50 wt% CaF2/50SiO2 NCs exhibited more cumulative F-release by 126% and more stable F-release rate than the counterpart filled with 50 wt% CaF2/50SiO2 NPs after immersed for 1800 h. And 55 wt% CaF2/50SiO2 NCs filled DRCs could inhibit the growth of S. mutans, reaching an antibacterial ratio of 93%. SIGNIFICANCE: The spray-dried CaF2/50SiO2 NCs are promising fillers for the development of high-performance multifunctional DRCs.

Dermal bioaccessibility and cytotoxicity of heavy metals in urban soils from a typical plateau city: Implication for human health.

The dermal exposure of heavy metals in contaminated urban soils poses huge environmental health risks globally. However, their dermal bioaccessibility and adverse effects on human skin cells were not fully understood. In this study, we measured the total and dermal bioaccessibility of Cr, As, Cd, Pb, and Cu in four selected urban soil samples from Kunming, Yunnan, China, and evaluated the cellular responses of these bioaccessible extracts on human keratinocytes (HaCaT). Among all the metals, only As in Soil-3 (S3) exceeded Chinese risk screening and Yunnan background values at 38.2 mg/kg. The average concentrations of Cr, As, Cd, Pb, and Cu in all soil samples were 47.79, 15.50, 3.11, 104.27, and 180.29 mg/kg respectively. Although relatively high concentrations of heavy metals were detected in soil samples, the highest dermal bioaccessibility of Cd was 3.57% with others' being lower than 1%. The bioaccessible dermal-absorbed doses (DADs) of Cr, As, Cd, Pb, and Cu from soils reflected acceptable health risks since all DADs were below the corresponding derived dermal reference values. However, the toxic data showed the extracts of S3 and S4 presented certain cytotoxicity in HaCaT cells, indicating the existing models based on dermal bioaccessibility and DADs may be not accurate enough to assess their human health risk. Taken together, the human health risk assessment should be modified by taking their skin cytotoxicity into account.

3D-Printed Strong Dental Crown with Multi-Scale Ordered Architecture, High-Precision, and Bioactivity.

Mimicking the multi-scale highly ordered hydroxyapatite (HAp) nanocrystal structure of the natural tooth enamel remains a great challenge. Herein, a bottom-up step-by-step strategy is developed using extrusion-based 3D printing technology to achieve a high-precision dental crown with multi-scale highly ordered HAp structure. In this study, hybrid resin-based composites (RBCs) with "supergravity +" HAp nanorods can be printed smoothly via direct ink writing (DIW) 3D printing, induced by shear force through a custom-built nozzle with a gradually shrinking channel. The theoretical simulation results of finite element method are consistent with the experimental results. The HAp nanorods are first highly oriented along a programmable printing direction in a single printed fiber, then arranged in a layer by adjusting the printing path, and finally 3D printed into a highly ordered and complex crown structure. The printed samples with criss-crossed layers by interrupting crack propagation exhibit a flexural strength of 134.1 ± 3.9 MPa and a compressive strength of 361.6 ± 8.9 MPa, which are superior to the corresponding values of traditional molding counterparts. The HAp-monodispersed RBCs are successfully used to print strong and bioactive dental crowns with a printing accuracy of 95%. This new approach can help provide customized components for the clinical restoration of teeth.

Efficient prediction of the packing density of inorganic fillers in dental resin composites for excellent properties.

OBJECTIVE: The purpose of this study is to develop a mathematical model for efficient prediction of the packing density of different filler formulations in dental resin composites (DRCs), and to study properties of DRCs at the maximum filler loading (MFL), thereby providing an effective guidance for the design of filler formulations in DRCs to obtain excellent properties. METHODS: The packing density data generated by discrete element model (DEM) simulation were used to re-derive the parameters of 3-parameter model. The modifier effect was also induced to modify the 3-parameter model. DRCs with 10 filler formulations were selected to test properties at the MFL. The packing densities of binary and ternary mixes in DRCs were calculated by 3-parameter model to explore the regularity of composite packing. RESULTS: The predicted packing density was validated by simulation and experimental results, and the prediction error is within 1.40 vol%. The optimization of filler compositions to obtain a higher packing density is beneficial to enhancing the mechanical properties and reducing the polymerization shrinkage of DRCs. In binary mixes, the maximum packing density occurs when the volume fraction of small fillers is 0.35-0.45, and becomes higher with the reduction of particle size ratio. In ternary mixes, the packing density can reach the maximum value when the volume fractions of large and small fillers are in the 0.5-0.75 and 0.15-0.4 ranges, respectively. SIGNIFICANCE: The modified 3-parameter model can provide an effective method to design the multi-level filler formulations of DRCs, thereby improving the performance of the materials.

Antibacterial activity and reinforcing effect of SiO2-ZnO complex cluster fillers for dental resin composites.

The accumulation of bacteria at the margin of dental resin composites is the main reason for secondary caries, which may further cause failure of prosthodontics. Therefore, antibacterial activity is highly required. However, the addition of antibacterial agents or fillers weakens the mechanical or aesthetic properties of composites. In this work, regular-shaped SiO2-ZnO complex clusters (CCs) constructed by spray-drying technology can enhance the antibacterial activity while maintaining the mechanical and aesthetic properties of dental resin composites. The results show that the regular shape and closely packed structure of nanoparticle clusters were not corrupted by the introduction of ZnO particles. As compared to resin composites filled with SiO2 nanoparticle clusters, the comprehensive performances of composites containing SiO2-ZnO CCs were further improved, and the composites filled with 70 wt% Si66Zn4 (CCs composed of 66/70 SiO2 and 4/70 of ZnO) exhibited superior antibacterial capability (antibacterial ratio >99.9%) and acceptable depth of cure, degree of conversion, and biocompatibility. The cooperation of different fillers is highly essential for resin composites to achieve enhanced multifunctional performance.

Extensive eye-oral-bronchial mucosal nodules with eosinopgillia: a rare case report and literature review.

BACKGROUND: Mucosal nodules can be caused by infection, inflammation and neoplastic disease. Many noninfectious diseases, such as eosinophilia, amyloidosis, sarcoidosis, Wegener's granuloma, langerhans cell histiocytosis etc., are associated with the formation of multisytem mucosal nodules, especially significant bronchial lesions. Detailed medical history, comprehensive metabolic profile, biopsy specimen and imaging examinations are required for differentiating among these disorders. The process of diagnosis and treatment of our patient's mucosal nodules was challenging, which could be helpful to similar cases. CASE PRESENTATION: We represent a case of a 29-year-old woman with plentiful nodules of unknown origin on extensive mucous membranes. Biopsy specimen reports inflammatory lesions with large numbers of neutrophils, lymphocytes, and varying degrees of eosinophils. Treatment of anti-infection, anti-tussive and anti-allergic was ineffective, but glucocorticoid showed great improvement to her symptoms. CONCLUSION: We experienced a rare case with plentiful nodules of unknown origin on extensive mucous membranes. She may be a specific phenotype of eosinophilia or may be a novel multisystem disease with respiratory system as the primary symptom. The diagnosis of our patient remains unclear, but tentative glucocorticoid therapy was beneficial.

A new method for predicting the maximum filler loading of dental resin composites based on DEM simulations and experiments.

OBJECTIVE: The inorganic fillers in dental resin composites can enhance their mechanical properties and reduce polymerization shrinkage. When the usage amount of inorganic fillers is closed to maximum filler loading (MFL), the composites will usually achieve optimal performances. This study aims to develop a method that can predict the MFL of dental resin composites for the optimization of filler formulations. METHODS: A method based on discrete element method (DEM) simulations and experiments was firstly developed to predict the MFL of spherical silica particles for single-level and multi-level filling. RESULTS: The results indicate that the presence of modifier can increase the MFL, and the MFL increment can be exponentially changed with the content of the modifier. Compared with the single-level filling, the addition of secondary fillers is beneficial to increase the MFL, and the increment can be affected by the particle size and size ratio. The prediction results show a good agreement with the experiment results. SIGNIFICANCE: The accuracy of prediction results indicates a great potential of DEM simulations as a numerical experimental method in studying the MFL, and provides an effective method for the optimization of filler formulations.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study.

OBJECTIVE: To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. DESIGN: Retrospective case series. SETTING: Tongji Hospital in Wuhan, China. PARTICIPANTS: Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. MAIN OUTCOME MEASURES: Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. RESULTS: The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

CYP1B1, VEGFA, BCL2, and CDKN1A Affect the Development of Chronic Obstructive Pulmonary Disease.

Purpose: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by poor airflow. The purpose of this study was to explore the mechanisms involved in the development of COPD. Patients and Methods: The mRNA expression profile GSE100281, consisting of 79 COPD and 16 healthy samples, was acquired from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between COPD samples and healthy samples were analyzed using the limma package. Functional enrichment analysis for the DEGs was carried out using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Furthermore, DEG-compound pairs were predicted using the Comparative Toxicogenomics Database. The KEGG metabolite IDs corresponding to the compounds were also obtained through the MetaboAnalyst pipeline. Based on the diffusion algorithm, the metabolite network was constructed. Finally, the expression levels of key genes were determined using quantitative PCR (qPCR). Results: There were 594 DEGs identified between the COPD and healthy samples, including 242 upregulated and 352 downregulated genes. A total of 696 DEG-compound pairs, such as BCL2-C00469 (ethanol) and BCL2-C00389 (quercetin) pairs, were predicted. CYP1B1, VEGFA, BCL2, and CDKN1A were included in the top 10 DEG-compound pairs. Additionally, 57 metabolites were obtained. In particular, hsa04750 (inflammatory mediator regulation of TRP channels)-C00469 (ethanol) and hsa04152 (AMPK signaling pathway)-C00389 (quercetin) pairs were found in the metabolite network. The results of qPCR showed that the expression of CYP1B1, VEGFA, BCL2, and CDKN1A was consistent with that predicted using bioinformatic analysis. Conclusion: CYP1B1, VEGFA, BCL2, and CDKN1A may play important functions in the development and progression of COPD.

Prevalence and risk factors of chronic obstructive pulmonary diseases in a Hlai community in Hainan Island of China.

OBJECTIVES: We investigated prevalence and risk factors of chronic obstructive pulmonary disease (COPD) in a population of Hlai (the Li) ethnicity, a major minority, in Qicha Town, Changjiang County, Hainan Province, PRC, during 2014. METHODS: All residents at the age of 40 years or older were interviewed with standardized questionnaires. Spirometry was performed to measure the possible airflow limitation. According to the GOLD criteria, post bronchodilator FEV1/FVC < 70% was defined as COPD. Case-control study was used to screen the risk factors by analyzing COPD group (212 cases) and non-COPD control group (236 cases). Single factor analysis and multiple factor logistic regression analysis were used as statistical methods. RESULTS: The prevalence of COPD in the residents at the age of 40 years or older of Hlai community was 5.07% (286/5637) (95% CI = 0.045-0.057). In the logistic regression analysis, the COPD prevalence was 5.07% (147/2901) in men and 5.08% (139/2736) in women, respectively, with odds ratio (OR) 1.003, 95% CI 0.790-1.272 and P > 0.05, suggesting that the sex did not affect the COPD prevalence in the investigated samples, but age (OR = 1.096), expectoration (OR = 87.917), locomotor activity limitation (OR = 3.908) and frequency of respiration (OR = 2.512) were risk factors and associated with the development of COPD. Notably, although the tobacco smoker in male and female COPD patients were 48.6% (54/111) and 4.0% (4/101), respectively, passive smokers in female with COPD were 45.6% (46/101). CONCLUSION: In the Hlai population aged ≥40 years, the COPD prevalence was 5.07%. Smoking, age, expectoration, locomotor activity limitation and frequency of respiration were risk factors of COPD in Hlai ethnicity.

Variants in multiple genes polymorphism association analysis of COPD in the Chinese Li population.

BACKGROUND: It is known that the contribution of risk alleles to chronic obstructive pulmonary disease (COPD) may vary between populations. Further, previous studies involving various ethnic groups have revealed associations between COPD and genetic polymorphisms in families with sequence similarity 13, member A (FAM13A), micro-RNA 2054 (MIR2054), SET domain containing protein 7 (SETD7), ring finger protein 150 (RNF150), hedgehog interacting protein (HHIP), and vascular endothelial growth factor A (VEGFA). Our objective was to explore the association between these gene polymorphism and COPD in members of Chinese Li minority population. MATERIALS AND METHODS: The Chinese Li population case-control study was conducted to assess genetic associations with COPD risk. Seven single nucleotide polymorphisms (SNPs) located on chromosome 4, including FAM13A, MIR2054, SETD7, RNF150, and HHIP, and nine SNPs in the VEGFA gene were genotyped among 234 cases and 240 controls using Sequenom Mass-ARRAY(®) platform. Linkage disequilibrium (LD) analysis was performed using Haploview software and the associations of the SNP frequencies with COPD were analyzed using chi-square (χ(2)) tests, genetic models analysis, and haplotype analysis. RESULTS: By χ(2) we found the minor allele "G" of rs17050782 was with increased COPD risk in allele model. In genetic models, we found the minor allele of rs7671167 (P=0.028 by dominant model) and rs17050782 (P=0.008 by recessive model) was associated with the increased risk of COPD disease. Likewise, an increased risk of developing COPD was associated with the "GGCGC" haplotype of VEGFA (odds ratio =1.48, 95% confidence interval =1.02-2.12, P=0.037). CONCLUSION: Our results were the first time to reveal that SNPs from FAM13A (rs7671167), SETD7 (rs17050782), and a haplotype of VEGFA ("GGCGC") are potential susceptibility loci associated with increased COPD risk in Chinese Li minority population.

Association of genetic polymorphisms with chronic obstructive pulmonary disease in the Hainan population: a case-control study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and the fifth most common cause of disability in the world by 2020. Recently, variants in the hypoxia-inducible factor 1α (HIF1A), cholinergic receptor, neuronal nicotinic, alpha polypeptide-5, and iron-responsive element-binding protein 2 gene (IREB2) genes were found to be associated with COPD. This study aims to identify whether the variations in these genes are related to COPD in the Hainan population of the People's Republic of China. PATIENTS AND METHODS: We genotyped 12 single nucleotide polymorphisms in a case-control study with 200 COPD cases and 401 controls from Hainan, People's Republic of China. Odds ratios and 95% confidence intervals were estimated using the chi-squared (χ(2)) test, genetic model analysis, haplotype analysis, and stratification analysis. RESULTS: In the genetic model analysis, we found that the genotype T/T of rs13180 of IREB2 decreased the COPD risk by 0.52-fold (P=0.025). But in the further stratification analysis, we failed to find the association between the selected single nucleotide polymorphisms with COPD risk in Han population. In addition, the haplotype analysis of HIF1A gene also was not found to be the possible haplotype associated with COPD risk. CONCLUSION: Our results support that IREB2 rs13180 is associated with COPD in Hainan population. And this is the first time the HIF1A polymorphisms in COPD in a Chinese population has been reported, although we failed to find any significant result.

Cytochrome P450 2C9 (CYP2C9) polymorphisms in Chinese Li population.

BACKGROUND: The frequencies of Cytochrome P450 2C9 (CYP2C9) genotypes were various between populations. The aim of this study was to investigate the frequencies of the major variants of the CYP2C9 in Chinese Li minority populations. METHODS: The promoter, exons and surrounding introns, and 3'-untranslated region of the CYP2C9 gene was detected by DNA sequencing to investigate in 100 unrelated healthy Chinese Li subjects. The protein function prediction was used the online tools: Sorting Intolerant From Tolerant (SIFT) and Phenotyping Version 2 (PolyPhen-2). The comparison of CYP2C9 allele frequencies in different populations were analyzed by Chi-square (χ(2)) test. Linkage disequilibrium (LD) analysis was performed using Haploview software. RESULTS: We identified 17 different CYP2C9 single nucleotide polymorphisms (SNPs) in the Li population, including two missense mutations (3549 G > A and 42614 A > C) and two silent mutations (3514 T > Cand 50298A > T). The protein function prediction revealed the two missense mutations result in protein damaging. In addition, we detected the allele frequencies of CYP2C9*1, CYP2C9*3 and CYP2C9*42 were 98%, 1%, and 1%, respectively. Finally, we compared three major allelic frequency (CYP2C9*1, CYP2C9*2, and CYP2C9*3) between Li and other populations. We found that our results were similar to East Asians and Africans.

Comparison of the efficacy and safety of mometasone furoate to other inhaled steroids for asthma: a meta-analysis.

BACKGROUND: It has been of great interest whether mometasone furoate (MF) is better than other inhaled corticosteroids (ICSs) as the controller therapy in patients with moderate or severe asthma who had previously been taking ICSs. OBJECTIVE: The aim of this meta-analysis is to thoroughly compare the efficacy and safety of MF versus other ICSs with equipotent daily doses in those patients. METHODS: Relative databases were searched. Randomised controlled trials of more than or equal to 4 weeks' treatment duration comparing MF with other ICSs were reviewed. RESULTS: Six trials with 1354 randomised patients met the inclusion criteria. Significant differences favouring MF were found in all indices of pulmonary function. MF was superior compared to other ICSs in decreasing the frequency of rescue medication use and morning difficulty breathing score. There was no significant difference between MF and other ICSs therapy in morning wheezing score, cough score and percentage of patients with no nocturnal awakenings due to asthma. For the treatment-related adverse effects (AEs), treatment-related severe AEs, discontinuations due to AEs and some common symptom of AEs, MF was all similar to other ICSs in their incidence. CONCLUSIONS: In adult patients with moderate or severe asthma who had previously been taking ICSs, MF was superior to other ICSs with equipotent daily doses as controller monotherapy in improving pulmonary function and decreasing the frequency of rescue medication use, and was similar to other ICSs in the incidence of AEs. These results demonstrated the priority of MF in asthma therapy.