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Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease, the risk of which can be increased by poor diet. The objective of this study was to evaluate the associations between food items and MAFLD, and to propose reasonable dietary recommendations for the prevention of MAFLD. Methods: Physical examination data were collected from April 2015 through August 2017 at Nanping First Hospital (n = 3,563). Dietary intakes were assessed using a semi-quantitative food frequency questionnaire. The association between food intake and the risk of MAFLD was assessed by using the inverse probability weighted propensity score. Results: Beverages (soft drinks and sugar-sweetened beverages) and instant noodles were positively associated with MAFLD risk, adjusting for smoking, drinking, tea intake, and weekly hours of physical activity [adjusted odds ratio (ORadjusted): 1.568; P = 0.044; ORadjusted: 4.363; P = 0.001]. Milk, tubers, and vegetables were negatively associated with MAFLD risk (ORadjusted: 0.912; P = 0.002; ORadjusted: 0.633; P = 0.007; ORadjusted: 0.962; P = 0.028). In subgroup analysis, the results showed that women [odds ratio (OR): 0.341, 95% confidence interval (CI): 0.172-0.676] had a significantly lower risk of MAFLD through consuming more tubers than men (OR: 0.732, 95% CI: 0.564-0.951). Conclusions: These findings suggest that reducing consumption of beverages (soft drinks and sugar-sweetened beverages) and instant noodles, and consuming more milk, vegetables, and tubers may reduce the risk of MAFLD.
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The associations of hand, foot, and mouth disease (HFMD) with meteorological variables and particulate matter (PM) remain controversial, and limited evidence is available on heat index (HI) and coarse particulate (PM10-2.5). Moreover, temperature and humidity are considered major risk factors but their interaction with PM remains unclear. We combined the distributed lag non-linear and quasi-Poisson models to estimate the non-linear and lagged associations of meteorological variables and PM with HFMD based on reported HFMD during 2015-2019 in Fuzhou, China. The multiplicative term of interaction was used to explore the relationship between HFMD and meteorological variables or PM at different levels of another variable. Stratified analyses were used to identify vulnerable subpopulations. We observed inverted-V-shaped relationships between HFMD and temperature and HI, and the W- and N-shaped for relative humidity (RH) and PM, respectively. Extreme high (i.e., the 95th percentile) temperature, HI and RH increased the HFMD with relative risks (RR) of 4.00 (95% confidence interval, 2.79-5.75), 2.20 (1.71-2.83) and 1.54 (1.35-1.75) referent to the minimum effect value of 10.3 °C, 69.4 and 54.8%, respectively. Higher concentrations of PM rapidly increased the HFMD. Infants under 2 years suffered more from temperature, HI and PM. There were synergistic effects between meteorological variables and PM on HFMD. For instance, the RRs of temperature (30 °C) and RH (40%) on HFMD increased from 3.68 (2.24-6.06) to 6.44 (4.29-9.66) and from 0.45 (0.14-1.47) to 2.15 (0.90-5.12) at low (<25%) and high (>75%) categories of PM2.5, respectively. While the RRs of 70 µg/m3 of PM10 and PM10-2.5 increased from 0.65 (0.32-1.31) to 2.93 (1.63-5.26) and from 0.86 (0.23-3.21) to 3.26 (1.23-8.62) at low and high categories of HI. These findings are essential for the development a prediction and warning systems and prevention and control strategies for HFMD.
Subject(s)
Hand, Foot and Mouth Disease , Particulate Matter , Infant , Child , Humans , Particulate Matter/analysis , Temperature , Hot Temperature , Hand, Foot and Mouth Disease/epidemiology , Humidity , Incidence , Risk Factors , China/epidemiology , Meteorological ConceptsABSTRACT
Background: The study purpose was to characterize the mycobiome and its associations with the expression of pathogenic genes in esophageal squamous cell carcinoma (ESCC). Methods: Patients with primary ESCC were recruited from two central hospitals. We performed internal transcribed spacer 1 (ITS1) ribosomal DNA sequencing analysis. We compared differential fungi and explored the ecology of fungi and the interaction of bacteria and fungi. Results: The mycobiota diversity was significantly different between tumors and tumor-adjacent samples. We further analysed the differences between the two groups, at the species level, confirming that Rhodotorula toruloides, Malassezia dermatis, Hanseniaspora lachancei, and Spegazzinia tessarthra were excessively colonized in the tumor samples, whereas Preussia persica, Fusarium solani, Nigrospora oryzae, Acremonium furcatum, Golovinomyces artemisiae, and Tausonia pullulans were significantly more abundant in tumor-adjacent samples. The fungal co-occurrence network in tumor-adjacent samples was larger and denser than that in tumors. Similarly, the more complex bacterial-fungal interactions in tumor-adjacent samples were also detected. The expression of mechanistic target of rapamycin kinase was positively correlated with the abundance of N. oryzae and T. pullulans in tumor-adjacent samples. In tumors, the expression of MET proto-oncogene, receptor tyrosine kinase (MET) had a negative correlation and a positive correlation with the abundance of R. toruloides and S. tessarthra, respectively. Conclusion: This study revealed the landscape of the esophageal mycobiome characterized by an altered fungal composition and bacterial and fungal ecology in ESCC.
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Cardiovascular disease (CVD) is a leading threat to global public health. Although associations between temperature and CVD hospitalization have been suggested for developed countries, limited evidence is available for developing countries or rural residents. Moreover, the effect of apparent temperature (AT) on the spectrum of cause-specific CVDs remains unknown. Based on 2,024,147 CVD hospitalizations for rural residents from eight regions in Fujian Province, China, during 2010-2016, a quasi-Poisson regression with distributed lag non-linear model was fitted to estimate the AT effect on daily CVD hospitalization for each region, and then pooled in a meta-regression that included regional indicators related to rural residents. Stratified analyses were performed according to the cause of hospitalization, sex and age groups. Finally, we calculated the fraction of CVD hospitalizations attributable to AT, as a reï¬ection of the burden associated with AT. The heat effect appeared at lag 0-1 days, with 19% (95% CI, 11-26%) increased risk of CVD hospitalization, which was worse for ischemic heart disease, heart failure, arrhythmias and ischemic stroke. The decreased AT was associated with increase of hemorrhagic stroke at lag 0-28 days. People aged 65 and above suffered more from the heat effect on cardiovascular and cerebrovascular diseases. Regions with a lower gross value of agricultural production, rural residents' per capita net income, number of air conditioners and water heaters were more susceptible. A large number of hospitalizations were attributable to heat for most subcategories. High AT level increased CVD hospitalization, and the subcategories had different susceptibilities. The effects were modified by individual and regional characteristics. These findings have important implications for the development of targeted interventions and for hospital service planning.
Subject(s)
Cardiovascular Diseases , Cardiovascular Diseases/epidemiology , China/epidemiology , Hospitalization , Hot Temperature , Humans , TemperatureABSTRACT
Background: Studies have shown inconsistent associations between serum uric acid (SUA) levels and mortality in peritoneal dialysis (PD) patients. We conducted this meta-analysis to determine whether SUA levels were associated with cardiovascular or all-cause mortality in PD patients. Methods: PubMed, Embase, Web of Science, the Cochrane Library, CNKI, VIP, Wanfang Database, and trial registry databases were systematically searched up to April 11, 2021. Cohort studies of SUA levels and cardiovascular or all-cause mortality in PD patients were obtained. Random effect models were used to calculate the pooled adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI). Sensitivity analyses were conducted to assess the robustness of the pooled results. Subgroup analyses and meta-regression analyses were performed to explore the sources of heterogeneity. Funnel plots, Begg's tests, and Egger's tests were conducted to evaluate potential publication bias. The GRADE approach was used to rate the certainty of evidence. This study was registered with PROSPERO, CRD42021268739. Results: Seven studies covering 18,113 PD patients were included. Compared with the middle SUA levels, high SUA levels increased the risk of all-cause mortality (HR = 1.74, 95%CI: 1.26-2.40, I 2 = 34.8%, τ2 = 0.03), low SUA levels were not statistically significant with the risk of all-cause or cardiovascular mortality (HR = 1.04, 95%CI: 0.84-1.29, I 2 = 43.8%, τ2 = 0.03; HR = 0.89, 95%CI: 0.65-1.23, I 2 = 36.3%, τ2 = 0.04; respectively). Compared with the low SUA levels, high SUA levels were not statistically associated with an increased risk of all-cause or cardiovascular mortality (HR = 1.19, 95%CI: 0.59-2.40, I 2 = 88.2%, τ2 = 0.44; HR = 1.22, 95%CI: 0.39-3.85, I 2 = 89.3%, τ2 = 0.92; respectively). Conclusion: Compared with middle SUA levels, high SUA levels are associated with an increased risk of all-cause mortality in PD patients. SUA levels may not be associated with cardiovascular mortality. More high-level studies, especially randomized controlled trials, are needed to determine the association between SUA levels and cardiovascular or all-cause mortality in PD patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021268739, identifier: CRD42021268739.
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The coronavirus disease-19 (COVID-19) pandemic has put healthcare workers in an unprecedented situation, increasing their psychological and mental health distress. Much research has focused on the issues surrounding anxiety, depression, and stress among healthcare workers. The consequences of mental health problems on healthcare workers' physical health, health-compromising behaviours, suicide ideation, family relationships, and job satisfaction during the COVID-19 pandemic are not well studied. Enhanced psychological stress has known effects on an individual's physical health. In healthcare workers with pre-existing comorbidities, psychological stressors may exacerbate their current health problems. Healthcare professionals are known to have a high risk of substance use, hence they may be at risk of development of substance use addiction or vulnerable to addiction relapse. Frontline COVID-19 healthcare workers are being pushed above and beyond their limits, possibly resulting in suicidal tendencies. Furthermore, the burden of high workload and burnout may also have serious manifestations in relationships with family and an intention to quit their jobs. Future studies should explore the above-mentioned deleterious consequences to provide insight into the development of mental healthcare strategies to combat the psychological impact of COVID-19 on healthcare workers during the COVID-19 emergency. It is imperative to employ strategies to care for and policies to protect the psychological well-being of healthcare workers.
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BACKGROUND: The prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing and emerging as a global health burden. In addition to environmental factors, numerous studies have shown that genetic factors play an important role in the development of NAFLD. Copy number variation (CNV) as a genetic variation plays an important role in the evaluation of disease susceptibility and genetic differences. The aim of the present study was to assess the contribution of CNV to the evaluation of NAFLD in a Chinese population. METHODS: Genome-wide analysis of CNV was performed using high-density comparative genomic hybridisation microarrays (ACGH). To validate the CNV regions, TaqMan real-time quantitative PCR (qPCR) was utilized. RESULTS: A total of 441 CNVs were identified, including 381 autosomal CNVs and 60 sex chromosome CNVs. By merging overlapping CNVs, a genomic CNV map of NAFLD patients was constructed. A total of 338 autosomal CNVRs were identified, including 275 CNVRs with consistent trends (197 losses and 78 gains) and 63 CNVRs with inconsistent trends. The length of the 338 CNVRs ranged from 5.7 kb to 2.23 Mb, with an average size of 117.44 kb. These CNVRs spanned 39.70 Mb of the genome and accounted for ~ 1.32% of the genome sequence. Through Gene Ontology and genetic pathway analysis, we found evidence that CNVs involving nine genes may be associated with the pathogenesis of NAFLD progression. One of the genes (NLRP4 gene) was selected and verified by quantitative PCR (qPCR) method with large sample size. We found the copy number deletion of NLRP4 was related to the risk of NAFLD. CONCLUSIONS: This study indicate the copy number variation is associated with NAFLD. The copy number deletion of NLRP4 was related to the risk of NAFLD. These results could prove valuable for predicting patients at risk of developing NAFLD.
Subject(s)
Non-alcoholic Fatty Liver Disease , Biomarkers , Comparative Genomic Hybridization , DNA Copy Number Variations , Genome , Humans , Non-alcoholic Fatty Liver Disease/genetics , Polymorphism, Single NucleotideABSTRACT
Aim: To explore the relationship between Chlamydia pneumonia (Cpn) infection and lung cancer using integrative methylome and transcriptome analyses. Methods: Twelve primary lung cancer patients who were positive for Cpn and twelve patients who were negative were selected for demographic, clinicopathological, and lifestyle matching. Genomic DNA and RNA were extracted and DNA methylation and mRNA levels were detected using the Infinium Human Methylation 450 Beadchip array and mRNA + lncRNA Human Gene Expression Microarray. We identified differentially expressed methylation and genes profiles. Results: Integrative analysis revealed an inverse correlation between differentially expressed genes and DNA methylation. Cpn-related lung cancer methylated genes (target genes) were introduced into the gene ontology and KEGG, PID, BioCarta, Reactome, BioCyc and PANTHER enrichment analyses using a q-value cutoff of 0.05 to identify potentially functional methylation of abnormal genes associated with Cpn infection. Gene sets enrichment analysis was evaluated according to MsigDB. Levels of differentially expressed methylated sites were quantitatively verified. The promoter methylation sites of 62 genes were inversely related to expression levels. According to the quantitative analysis of DNA methylation, the methylation level of the RIPK3 promoter region was significantly different between Cpn-positive cancerous and adjacent tissues, but not between Cpn-negative cancerous and adjacent tissues. Conclusion: Hypomethylation of the RIPK3 promoter region increases RIPK3 expression, leading to regulated programmed necrosis and activation of NF-κB transcription factors, which may contribute to the development and progression of Cpn-related lung cancer.
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BACKGROUND: We investigated whether BCMO1 variants and dietary patterns are associated with lung cancer risk. METHODS: Case-control study including 1166 lung cancer cases and 1179 frequency matched controls was conducted for three BCMO1 variants (rs6564851, rs12934922, and rs7501331) and four dietary patterns were investigated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: The rs6564851, rs12934922, and rs7501331 were not found to be associated with lung cancer risk (P > 0.05). In multivariable-adjusted models, compared to the lowest quartile of the score on the "fruits and vegetables" pattern, the highest quintile was associated with a 78.4% decreased risk (OR Q4 vs. Q1 = 0.216; 95% CI, 0.164-0.284; P for trend < 0.001). Other patterns were not found the association. The "fruits and vegetables" pattern was associated with a reduced risk of lung cancer with all 3 SNPs irrespective of genotypes (all P for trend< 0.001). The association for the "Frugal" pattern was associated with increased risk of lung cancer among smokers (P for interaction = 0.005). The protective effects of the "cereals/wheat and meat" pattern was more evident for squamous cell carcinoma and other histological type. CONCLUSIONS: We did not observe associations of BCMO1 variants and lung cancer. Diets rich in fruits and vegetables may be protective against lung cancer.
Subject(s)
Feeding Behavior , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Polymorphism, Genetic , beta-Carotene 15,15'-Monooxygenase/genetics , Aged , Alleles , Case-Control Studies , China/epidemiology , Female , Genotype , Humans , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide , Risk Assessment , Risk FactorsABSTRACT
It remains challenging to forecast local, seasonal outbreaks of influenza. The goal of this study was to construct a computational model for predicting influenza incidence. We built two computational models including an Autoregressive Distributed Lag (ARDL) model and a hybrid model integrating ARDL with a Generalized Regression Neural Network (GRNN), to assess meteorological factors associated with temporal trends in influenza incidence. The modelling and forecasting performance of these two models were compared using observations collected between 2006 and 2015 in Nagasaki Prefecture, Japan. In both the training and forecasting stages, the hybrid model showed lower error rates, including a lower residual mean square error (RMSE) and mean absolute error (MAE) than the ARDL model. The lag of log-incidence, weekly average barometric pressure, and weekly average of air temperature were 4, 1, and 3, respectively in the ARDL model. The ARDL-GRNN hybrid model can serve as a tool to better understand the characteristics of influenza epidemic, and facilitate their prevention and control.
Subject(s)
Influenza, Human/epidemiology , Models, Theoretical , Computer Simulation , Forecasting , Humans , Incidence , Japan/epidemiology , Population Surveillance , Reproducibility of Results , Risk Factors , TemperatureABSTRACT
The reactions of pyrrolidine derived salalen-type {ONNO} ligands (S)-L1-3-H2 with 1 equiv. M(OiPr)4(HOiPr) (M = Zr or Hf) in diethyl ether yielded complexes [L1-3M(OiPr)2] (L = L1, M = Zr (1); L = L2, M = Zr (2), Hf (3); L = L3, M = Zr (4), Hf (5)). All of these complexes were well characterized by NMR spectroscopy, elemental analyses and single-crystal X-ray analysis in the case of complexes 1 and 3-5. X-ray structural determination revealed that these complexes were analogous mononuclear species and had a similar structure in which the metal centers were six-coordinated to two oxygen atoms and two nitrogen atoms of one ligand and two oxygen atoms of two isopropoxy groups. All of these complexes efficiently initialized the ring-opening polymerization of lactides to afford polymers with controlled molecular weight and narrow polydispersity. Furthermore, the ring-opening polymerization of rac-lactide catalyzed by complexes 1-5 afforded isotactic-enriched polymers in solution (Pm = 0.74-0.80) and under melt conditions (Pm = 0.63-0.72).
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BACKGROUND: The purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. METHODS: A 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation. RESULTS: Current or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21-4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene-tea drinking: P(interaction) = 0.042; hot beverage/food consumption: P(interaction) = 6.98 × 10(-6)) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12-3.80). CONCLUSIONS: Our findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.
Subject(s)
Asian People/genetics , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Cytochrome P-450 CYP2C19/genetics , Environment , Esophageal Neoplasms/enzymology , Esophageal Neoplasms/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide , Carcinoma, Squamous Cell/epidemiology , China/epidemiology , Esophageal Neoplasms/epidemiology , Esophageal Squamous Cell Carcinoma , Female , Humans , Male , Middle Aged , Risk FactorsABSTRACT
BACKGROUND: NAD (P)H:quinone oxidoreductase (NQO1) catalyzes the activation of some environmental procarcinogens present in tobacco smoke or the diet. We conducted a hospital-based case-control study to evaluate the potential association between NQO1 609C>T polymorphisms and colorectal cancer risk in a Chinese population. METHODS: The study population comprised 672 histologically confirmed colorectal cancer patients and 672 frequency-matched control subjects without cancer or systemic illness. We used PCR restriction fragment length polymorphism-based methods for genotyping analyses and unconditional logistic regression model for statistical evaluations. RESULTS: The risk of colorectal cancer increased with the level of smoking and decreased with the consumption of tea, fresh fruits, and vegetables. In addition, we found that the NQO1 609 CT and TT genotypes were associated with an increased risk of colorectal cancer (CT: adjusted OR=2.02, 95% CI=1.55-2.57; TT: adjusted OR=2.51, 95% CI=1.82-3.47), compared with the CC genotype. Moreover, NQO1 609C>T appeared to have a multiplicative joint effect with both tobacco smoking and alcoholic drinking (P for multiplicative interactions were 0.0001 and 0.013, respectively) on colorectal cancer risk. CONCLUSION: Our findings suggest that the NQO1 609C>T polymorphism plays an important role in the development of colorectal cancer in the Chinese population, which is strengthened by alcohol drinking or tobacco smoking.
Subject(s)
Alcohol Drinking/genetics , Colorectal Neoplasms/genetics , Genetic Predisposition to Disease , NAD(P)H Dehydrogenase (Quinone)/genetics , Polymorphism, Single Nucleotide , Smoking/genetics , Adult , Aged , Alcohol Drinking/adverse effects , Asian People/genetics , Case-Control Studies , Diet , Female , Fruit , Gene-Environment Interaction , Humans , Male , Middle Aged , Polymorphism, Restriction Fragment Length , Smoking/adverse effects , VegetablesABSTRACT
Adult-onset Still's disease (AOSD) is a systemic inflammatory autoimmune disorder of unknown etiology and pathogenesis. There are no specific laboratory tests for AOSD. To investigate the potential role of adenosine deaminase (ADA) in the diagnosis of AOSD and analyze the correlation among ADA, LDH and WBC (white blood cell count), the serum levels of ADA and LDH in 26 patients with active untreated AOSD, 40 patients with active systemic lupus erythematosus (SLE) as disease control and 48 healthy volunteers as healthy control were determined using automatic biochemical analyzer (Olympus AU2700, Japan). WBC was examined by automatic blood cell analyzer (Beckman Coulter Hmx, America). Significantly higher levels of serum ADA, LDH and WBC were found in active untreated AOSD patients than in active SLE patients and healthy volunteers (F = 27.823; P = 0.000; F = 28.458, P = 0.000; F = 51.929, P = 0.000). Serum ADA were related to LDH level in patients with AOSD patients (r = 0.786, P = 0.000 < 0.01). Both ADA and LDH were not related to WBC (r = 0.244, P = 0.229 > 0.01; r = 0.054, P = 0.794 > 0.01). This is the first study to show that serum ADA could play an important role in AOSD and may be an important biomarker for the diagnosis of AOSD. Serum ADA could be another diagnostic marker independent from whole blood WBC.
Subject(s)
Adenosine Deaminase/blood , Clinical Enzyme Tests , Still's Disease, Adult-Onset/diagnosis , Adult , Analysis of Variance , Biomarkers/blood , Case-Control Studies , Female , Humans , L-Lactate Dehydrogenase/blood , Leukocyte Count , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Male , Predictive Value of Tests , Still's Disease, Adult-Onset/blood , Up-Regulation , Young AdultABSTRACT
We investigated the possible association between genetic variants in the Patatin like phospholipase-3 (PNPLA3) gene and nonalcoholic fatty liver disease (NAFLD) in a Han Chinese population. We evaluated twelve tagging single-nucleotide polymorphisms (tSNPs) of the PNPLA3 gene in a frequency matched case-control study from Fuzhou city of China (553 cases, 553 controls). In the multivariate logistic regression analysis, the rs738409 GG or GC, and rs139051 TT genotypes were found to be associated with increased risk of NAFLD, and a significant trend of increased risk with increasing numbers of risk genotype was observed in the cumulative effect analysis of these single nucleotide polymorphisms. Furthermore, haplotype association analysis showed that, compared with the most common haplotype, the CAAGAATGCGTG and CGAAGGTGTCCG haplotypes conferred a statistically significant increased risk for NAFLD, while the CGGGAACCCGCG haplotype decreased the risk of NAFLD. Moreover, rs738409 C>G appeared to have a multiplicative joint effect with tea drinking (P<0.005) and an additive joint effect with obesity (Interaction contrast ratio (ICR)â=â2.31, 95% CI: 0.7-8.86), hypertriglyceridemia (ICRâ=â3.07, 95% CI: 0.98-5.09) or hypertension (ICRâ=â1.74, 95% CI: 0.52-3.12). Our data suggests that PNPLA3 genetic polymorphisms might influence the susceptibility to NAFLD development independently or jointly in Han Chinese.
Subject(s)
Asian People , Fatty Liver/genetics , Lipase/genetics , Liver/enzymology , Membrane Proteins/genetics , Polymorphism, Single Nucleotide , Adult , Alleles , Case-Control Studies , Fatty Liver/complications , Fatty Liver/enzymology , Fatty Liver/ethnology , Female , Genetic Predisposition to Disease , Haplotypes , Humans , Hypertension/complications , Hypertension/enzymology , Hypertension/ethnology , Hypertension/genetics , Hypertriglyceridemia/complications , Hypertriglyceridemia/enzymology , Hypertriglyceridemia/ethnology , Hypertriglyceridemia/genetics , Lipase/metabolism , Liver/pathology , Male , Membrane Proteins/metabolism , Middle Aged , Non-alcoholic Fatty Liver Disease , Obesity/complications , Obesity/enzymology , Obesity/ethnology , Obesity/genetics , Risk , TeaABSTRACT
AIM: To construct an eukaryotic expression vector for RNA interference targeting activating transcription factor 2 (ATF-2) gene, and explore its effect on proliferation and apoptosis of HepG2 cells. METHODS: Two complementary oligonucleotides were synthesized based on ATF-2 mRNA sequence. The annealed fragment was inserted into the vector PBA-siU6. The recombinant plasmid PBA-siATF-2 was confirmed by DNA sequencing and transfected into HepG2 cells mediated by liposome. After transfection, ATF-2 protein was detected by Western blotting. The cellular growth activity and apoptosis rate were measured by MTT assay and flow cytometry, respectively. RESULTS: Recombinant plasmid expressing siRNA targeting ATF-2 gene was confirmed by DNA sequencing. Plasmid transfection down-regulated the level of ATF-2 protein in HepG2 cells, which blocked cellular growth and induced cell apoptosis. CONCLUSION: The eukaryotic expression vector for RNA interference targeting ATF-2 gene was constructed successfully, which inhibits HepG2 cell proliferation and induces cell apoptosis.
Subject(s)
Activating Transcription Factor 2/genetics , Genetic Therapy , Genetic Vectors , RNA, Small Interfering/genetics , Apoptosis , Base Sequence , Cell Proliferation , Hep G2 Cells , Humans , Molecular Sequence Data , TransfectionABSTRACT
Liver fatty acid-binding protein (FABP1) serves as a key regulator of hepatic lipid metabolism, and polymorphisms within the FABP1 gene have been associated with several metabolic traits. To investigate the association between FABP1 polymorphisms and the risk of non-alcohol fatty liver disease (NAFLD) in a Chinese population, the genotypes and haplotypes of FABP1 (rs2241883 T/C and rs1545224G/A) were determined in 553 patients with NAFLD and 553 healthy controls. The results showed that individuals with at least one copy of the rs2241883 C allele (TC or CC genotype) had an elevated risk for developing NAFLD (odds ratio [OR]=1.32, 95% CI: 1.01-1.71), and individuals with at least one copy of the rs1545224 A allele (GA or AA genotype) also had a significantly increased risk for NAFLD (OR=1.52, 95% CI: 1.14-2.02). Cumulative effect analysis of the two SNPs revealed that individuals with two risk genotypes were at significantly higher risk of NAFLD than those without risk genotype, and a significant trend of increased risk with increasing numbers of risk genotype was observed. Stratification analysis showed that the rs2241883 C allele carriers had higher level of LDL-C and the rs1545224 A allele carriers had higher level of FPG than those without this allele. In addition, haplotype analysis revealed that the one composed of the rs1545224 A and rs2241883 C variants was significantly associated with an increased risk for NAFLD (OR=1.34; 95% CI=1.05-1.40) compared to the GT haplotype. Taken together, the present study suggests that genetic variations within FABP1 influence susceptibility to NAFLD independently or jointly.
Subject(s)
Fatty Acid-Binding Proteins/genetics , Fatty Liver/ethnology , Fatty Liver/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Adult , Aged , Asian People/genetics , Female , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease , Young AdultSubject(s)
Genes, p53 , Liver Neoplasms/metabolism , Liver/drug effects , Microcystins/toxicity , Animals , Gene Expression , Liver/metabolism , Liver/pathology , Liver Neoplasms/pathology , Male , Marine Toxins , Mutation , Rats , Rats, WistarABSTRACT
AIM: To assess the application of the Kasai procedure in the surgical management of hilar bile duct strictures. METHODS: Ten consecutive patients between 2005 and 2011 with hilar bile duct strictures who underwent the Kasai procedure were retrospectively analyzed. Kasai portoenterostomy with the placement of biliary stents was performed in all patients. Clinical characteristics, postoperative complications, and long-term outcomes were analyzed. All patients were followed up for 2-60 mo postoperatively. RESULTS: Patients were classified according to the Bismuth classification of biliary strictures. There were two Bismuth III and eight Bismuth IV lesions. Six lesions were benign and four were malignant. Of the benign lesions, three were due to post-cholecystectomy injury, one to trauma, one to inflammation, and one to inflammatory pseudotumor. Of the malignant lesions, four were due to hilar cholangiocarcinoma. All patients underwent Kasai portoenterostomy with the placement of biliary stents. There were no perioperative deaths. One patient experienced anastomotic leak and was managed conservatively. No other complications occurred perioperatively. During the follow-up period, all patients reported a good quality of life. CONCLUSION: The Kasai procedure combined with biliary stents may be appropriate for patients with hilar biliary stricture that cannot be managed by standard surgical methods.
Subject(s)
Anastomosis, Surgical/methods , Bile Ducts/pathology , Bile Ducts/surgery , Biliary Tract Surgical Procedures/methods , Constriction, Pathologic/surgery , Adult , Female , Humans , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Stents , Treatment OutcomeABSTRACT
OBJECTIVE: To explore the effects of microcystin-LR (MCLR) on the expression of base excision repair genes and genes related to apoptosis. METHODS: The BRL-3A cells were exposed to different concentrations of MCLR for various periods of time and the cell viability was measured by MTT. The mRNA expression was determined with the quantitative real-time polymerase chain reaction (QRT-PCR). RESULTS: The viability of BRL-3A cells significantly reduced in a concentration- and time-dependent manner. In 30 µg/ml group, the mRNA expression level (1.327 ± 0.028) of p53 increased significantly at 24 h after exposure, as compared with the other groups (1.005 ± 0.117, 0.862 ± 0.154, 1.028 ± 0.056 and 1.015 ± 0.091) (P < 0.05). The mRNA expression levels (5.080 ± 0.729, 5.820 ± 0.373, 6.018 ± 0.359 and 6.183 ± 0.515) of Bax in all exposure groups were significantly higher than that (1.024 ± 0.277) in control group at 24 h after exposure. However, the Bax mRNA expression level (0.604 ± 0.146) in the 30 µg/ml group at 72 h after exposure was significantly lower than those (1.004 ± 0.107, 0.811 ± 0.142, 0.855 ± 0.101 and 0.814 ± 0.056) in other groups (P < 0.05). When compared with control group (1.006 ± 0.132) and 1 µg/ml group (1.034 ± 0.241), the mRNA expression level (0.488 ± 0.147) of PARP1 in 30 µg/ml group at 48 h after exposure decreased significantly (P < 0.05). Furthermore, the mRNA expression levels (0.594 ± 0.180, 0.491 ± 0.015 and 0.305 ± 0.091) of JWA, XRCC1 and PARP1 in 30 µg/ml group at 72 h after exposure decreased significantly, as compared with the other groups (P < 0.05). CONCLUSION: The induction of gene expression is a transient phenomenon that occurred at different times of exposure for different genes. Inhibition of MCLR on the base excision repair gene expression may play important role in the course of MCLR promoting liver tumor.