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PURPOSE: This study aims to assess the prognostic value of the fatty liver index (FLI), a noninvasive tool for hepatic steatosis assessment, in predicting all-cause and disease-specific mortality. METHODS: We linked data from the National Health and Nutrition Examination Survey III (1988-1994) with Public-Use Mortality Files, forming a cohort of 11â 297 participants with a median follow-up period of 26.25â years. Cox proportional hazards models were used to evaluate the association between FLI and all-cause mortality, while Fine and Gray's models assessed the relationship between FLI and disease-specific mortality. RESULTS: The FLIâ ≥â 60 was independently associated with an increased risk of all-cause mortality (hazard ratioâ =â 1.24, P â <â 0.001), as well as mortality from malignant neoplasms (hazard ratioâ =â 1.18, P â =â 0.048), diabetes (hazard ratioâ =â 2.62, P â =â 0.001), and cardiovascular diseases (CVDs) (hazard ratioâ =â 1.18, P â =â 0.018), compared to FLIâ <â 30. No significant associations were found with Alzheimer's disease, influenza and pneumonia, chronic lower respiratory diseases, or renal disorders. Subgroup analyses indicated that individuals who were females aged 40-60 (hazard ratioâ =â 1.67, P â =â 0.003), non-overweight (hazard ratioâ =â 1.75, P â =â 0.007), or without abdominal obesity (hazard ratioâ =â 1.75, P â =â 0.007) exhibited a stronger association between FLIâ ≥â 60 and all-cause mortality. CONCLUSION: These findings support the prognostic value of the FLI for predicting mortality from all causes, malignant neoplasms, diabetes, and CVDs. Targeted attention is needed in postmenopausal women, non-overweight, and non-abdominally obese populations.
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Causas de Morte , Inquéritos Nutricionais , Modelos de Riscos Proporcionais , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Prognóstico , Fatores de Risco , Doenças Cardiovasculares/mortalidade , Valor Preditivo dos Testes , Neoplasias/mortalidade , Idoso , Medição de Risco/métodos , Estados Unidos/epidemiologia , Fatores de Tempo , Hepatopatia Gordurosa não Alcoólica/mortalidade , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
Background: This study aims to analyze the trend of Hepatitis B incidence in Xiamen City from 2004 to 2022, and to select the best-performing model for predicting the number of Hepatitis B cases from 2023 to 2027. Methods: Data were obtained from the China Information System for Disease Control and Prevention (CISDCP). The Joinpoint Regression Model analyzed temporal trends, while the Age-Period-Cohort (APC) model assessed the effects of age, period, and cohort on hepatitis B incidence rates. We also compared the predictive performance of the Neural Network Autoregressive (NNAR) Model, Bayesian Structural Time Series (BSTS) Model, Prophet, Exponential Smoothing (ETS) Model, Seasonal Autoregressive Integrated Moving Average (SARIMA) Model, and Hybrid Model, selecting the model with the highest performance to forecast the number of hepatitis B cases for the next five years. Results: Hepatitis B incidence rates in Xiamen from 2004 to 2022 showed an overall declining trend, with rates higher in men than in women. Higher incidence rates were observed in adults, particularly in the 30-39 age group. Moreover, the period and cohort effects on incidence showed a declining trend. Furthermore, in the best-performing NNAR(10, 1, 6)[12] model, the number of new cases is predicted to be 4271 in 2023, increasing to 5314 by 2027. Conclusions: Hepatitis B remains a significant issue in Xiamen, necessitating further optimization of hepatitis B prevention and control measures. Moreover, targeted interventions are essential for adults with higher incidence rates.
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Background: Reinfection of coronavirus disease 2019 (COVID-19) has raised concerns about how reliable immunity from infection and vaccination is. With mass testing for the virus halted, understanding the current prevalence of COVID-19 is crucial. This study investigated 1,191 public health workers at the Xiamen Center for Disease Control, focusing on changes in antibody titers and their relationship with individual characteristics. Methods: The study began by describing the epidemiological characteristics of the study participants. Multilinear regression (MLR) models were employed to explore the associations between individual attributes and antibody titers. Additionally, group-based trajectory models (GBTMs) were utilized to identify trajectories in antibody titer changes. To predict and simulate future epidemic trends and examine the correlation of antibody decay with epidemics, a high-dimensional transmission dynamics model was constructed. Results: Analysis of epidemiological characteristics revealed significant differences in vaccination status between infected and non-infected groups (χ2=376.706, P<0.05). However, the distribution of antibody titers among the infected and vaccinated populations was not significantly different. The MLR model identified age as a common factor affecting titers of immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibody (NAb), while other factors showed varying impacts. History of pulmonary disease and hospitalization influenced IgG titer, and factors such as gender, smoking, family history of pulmonary diseases, and hospitalization impacted NAb titers. Age was the sole determinant of IgM titers in this study. GBTM analysis indicated a "gradual decline type" trajectory for IgG (95.65%), while IgM and NAb titers remained stable over the study period. The high-dimensional transmission dynamics model predicted and simulated peak epidemic periods in Xiamen City, which correlated with IgG decay. Age-group-specific simulations revealed a higher incidence and infection rate among individuals aged 30-39 years during both the second and third peaks, followed by those aged 40-49, 50-59, 18-29, and 70-79 years. Conclusions: Our study shows that antibody titer could be influenced by age, previous pulmonary diseases as well as smoking. Furthermore, the decline in IgG titers is consistent with epidemic trends. These findings emphasize the need for further exploration of these factors and the development of optimized self-protection countermeasures against reinfection.
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In eukaryotic genomes, rDNA generally resides as a highly repetitive and dynamic structure, making it difficult to study. Here, a synthetic rDNA array on chromosome III in budding yeast was constructed to serve as the sole source of rRNA. Utilizing the loxPsym site within each rDNA repeat and the Cre recombinase, we were able to reduce the copy number to as few as eight copies. Additionally, we constructed strains with two or three rDNA arrays and found that the presence of multiple arrays did not affect the formation of a single nucleolus. Although alteration of the position and number of rDNA arrays did impact the three-dimensional genome structure, the additional rDNA arrays had no deleterious influence on cell growth or transcriptomes. Overall, this study sheds light on the high plasticity of rDNA organization and opens up opportunities for future rDNA engineering.
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Saccharomycetales , Saccharomycetales/genética , Ciclo Celular , Nucléolo Celular , Proliferação de Células , DNA Ribossômico/genéticaRESUMO
Background: The pivotal phase 3 efficacy clinical trial has demonstrated that a two-dose regimen of dNS1-RBD (Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) is well-tolerated and provides wide protection against SARS-CoV-2 infection. However, the effectiveness of a single-dose regimen is still unknown. We aimed to estimate the effectiveness of one-dose of dNS1-RBD against symptomatic Omicron infections in real-world conditions. Methods: This prospective cohort study was conducted during an Omicron outbreak among healthcare workers in Xiamen, China, from December 22, 2022 to January 16, 2023. Participants chose to receive single-dose of dNS1-RBD or remain unvaccinated based on personal preference. Healthcare workers daily validated their SARS-CoV-2 infection status, using either RT-PCR or rapid antigen test. A survey questionnaire was conducted to gather information on acute symptoms from individuals infected with SARS-CoV-2. The primary outcome was the symptomatic SARS-CoV-2 infections after enrollment in the dNS1-RBD recipients or the control group among all participants and by prior COVID-19 vaccination status. Findings: On December 22, 2022, a total of 1391 eligible participants without a history of prior SARS-CoV-2 infection were enrolled. Among them, 550 received single-dose of dNS1-RBD, while 841 remained unvaccinated. In the total cohort, the range of follow-up time was 1â¼26 days. During the study period, a total of 880 symptomatic SARS-CoV-2 infections were identified in the total cohort. The adjusted vaccine effectiveness against symptomatic SARS-CoV-2 infections and the infections requiring medical attention were 19.0% (95% CI: 6.7, 29.7, P = 0.004) and 59.4% (95% CI: 25.1, 78.0, P = 0.004) in the total cohort, 11.6% (95% CI: -2.4, 23.7, P = 0.100) and 55.3% (95% CI: 15.3, 76.4, P = 0.014) in the participants with inactivated COVID-19 vaccination history, as well as 87.0% (95% CI: 72.6, 93.9, P < 0.001) and 84.2% (95% CI: -41.8, 98.2, P = 0.099) in the naïve participants, respectively. Interpretation: When administered as a booster to individuals with a history of inactivated COVID-19 vaccination, a single-dose of dNS1-RBD provides protection against infections requiring medical attention at least in the short-term after vaccination. The data also showed that a single-dose of dNS1-RBD is protective against symptomatic SARS-CoV-2 infections as a primary immunization for individuals without prior exposure, but due to the limited sample size of naïve participants, further research with a larger sample size is needed to make a solid conclusion. Funding: Xiamen Science and Technology Bureau 2022 General Science and Technology Plan Project and the Bill & Melinda Gates Foundation.
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The effects of drawing parameters and annealing process on the properties and microstructure of single crystal copper wire are studied using a wire-drawing machine, heat-treatment equipment, microcomputer-controlled electronic universal tester, resistance tester, and scanning electron microscope. The results show that, after drawing the single-crystal copper wire with a single-pass deformation of 14%, the grains elongate along the tensile direction, tensile strength increases from 500.83 MPa to 615.5 Mpa, and resistivity changes from 1.745 × 10-8 Ω·m to 1.732 × 10-8 Ω·m. After drawing at a drawing rate of 500 m/min, the degree of grain refinement increases and tensile strength increases from 615.5 Mpa to 660.26 Mpa. When a copper wire of Φ0.08 mm is annealed, its tensile strength decreases from 660.26 Mpa to 224.7 Mpa, and elongation increases from 1.494% to 19.87% when the annealing temperature increases to 400 °C. When the annealing temperature increases to 550 °C, the tensile strength and elongation decrease to 214.4 MPa and 12.18%, respectively.
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The effects of various drawing parameters and annealing processes on the structure and properties of Cu-Ag wires, containing 1 wt% silver, were investigated using specialized equipment including fine wire-drawing machines, very fine wire-drawing machines, heat treatment equipment, tensile testing machines, microcomputer-controlled electronic universal testers, resistance testers, and scanning electron microscopes. The results revealed that continuous drawing of Cu-1%Ag alloy wires led to elongation of the grains, resulting in a uniform and tightly fibrous microstructure. Moreover, the tensile strength of the alloy wire increased from 670 MPa to 783.9 MPa after a single pass with a deformation of 14%. Subsequently, when the wire was drawn at a speed of 500 m/min, the tensile strength further increased to 820.1 MPa. After annealing the Õ0.08 mm Cu-1% Ag alloy wire, an increase in annealing temperature up to 500 °C resulted in the wire's tensile strength decreasing from 820.1 MPa to 377.5 MPa. Simultaneously, the elongation increased from 1.94% to 15.21%, and the resistivity decreased from 1.931 × 10-8 Ω·m to 1.723 × 10-8 Ω·m. Additionally, when annealing was conducted at a rate of 80 m/min, the wire resistivity dropped to 1.635 × 10-8 Ω·m.
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OBJECTIVE: Vaccine effectiveness can measure herd immunity, but the effectiveness of inactivated vaccines in Xiamen remains unclear. Our study was designed to understand the herd immunity of the COVID-19 inactivated vaccine against the SARA-CoV-2 Delta variant in the real world of Xiamen. METHODS: We carried out a test-negative case-control study to explore the vaccine's effectiveness. Participants aged over 12 years were recruited. A logistic regression was used to estimate the odds ratio (OR) of the vaccine among cases and controls. RESULTS: This outbreak began with factory transmission clusters, and spread to families and communities during the incubation period. Sixty percent of cases were confirmed in a quarantine site. A huge mass of confirmed cases (94.49%) was identified within three days, and nearly half of them had a low Ct value. Following an adjustment for age and sex, a single dose of inactivated SARS-CoV-2 vaccine yielded the vaccine effectiveness (VE) of the overall case, of 57.01% (95% CI: -91.44~86.39%), the fully VE was 65.72% (95% CI: -48.69~88.63%) against COVID-19, 59.45% against moderate COVID-19 and 38.48% against severe COVID-19, respectively. The VE of fully vaccinated individuals was significantly higher in females than in males (73.99% vs. 46.26%). The VE among participants aged 19~40 and 41~61 years was 78.75% and 66.33%, respectively, which exceeds the WHO's minimal threshold. Nevertheless, the VE in people under 18 and over 60 years was not observed because of the small sample size. CONCLUSIONS: The single-dose vaccine had limited effectiveness in preventing infection of the Delta variant. The two doses of inactivated vaccine could effectively prevent infection, and clinical mild, moderate, and severe illness caused by the SARS-CoV-2 Delta variant in people aged 18-60 years in the real world.
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Objectives: To investigate the associations between the overall burden of comorbidity, inflammatory indicators in plasma and Ct values among the elderly with COVID-19. Methods: We conducted a retrospective observational study. The results of each nucleic acid test of during hospitalization were obtained. Linear regression models assessed the associations between the overall burden of comorbidity, inflammatory indicators in plasma and Ct values among the elderly. A causal mediation analysis was performed to assess the mediation effects of inflammatory indicators on the association between the overall burden of comorbidity and Ct values. Results: A total of 767 COVID-19 patients aged ≥ 60 years were included between April 2022 and May 2022. Patients with a high burden of comorbidity had significantly lower Ct values of the ORF gene than subjects with a low burden of comorbidity (median, 24.81 VS 26.58, P < 0.05). Linear regression models showed that a high burden of comorbidity was significantly associated with higher inflammatory responses, including white blood cell count, neutrophil count and C-reactive protein. Also, white blood cell count, neutrophil count, C-reactive protein and the overall burden of comorbidity assessed by age-adjusted Charlson comorbidity index were independent risk factors for the Ct values. A mediation analysis detected the mediation effect of white blood cells on the association between the burden of comorbidity and Ct values, with the indirect effect estimates of 0.381 (95% CI: 0.166, 0.632, P < 0.001). Similarly, the indirect effect of C-reactive protein was -0.307 (95% CI: -0.645, -0.064, P = 0.034). White blood cells and C-reactive protein significantly mediated the relationship between the burden of comorbidity and Ct values by 29.56% and 18.13% of the total effect size, respectively. Conclusions: Inflammation mediated the association between the overall burden of comorbidity and Ct values among elderly with COVID-19, which suggests that combined immunomodulatory therapies could reduce the Ct values for such patients with a high burden of comorbidity.
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COVID-19 , Idoso , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Proteína C-Reativa/análise , Inflamação/epidemiologia , ComorbidadeRESUMO
Wire bonding is still the most popular chip interconnect technology in microelectronic packaging and will not be replaced by other interconnect methods for a long time in the future. Au bonding wire has been a mainstream semiconductor packaging material for many decades due to its unique chemical stability, reliable manufacturing, and operation properties. However, the drastic increasing price of Au bonding wire has motivated the industry to search for alternate bonding materials for use in microelectronic packaging such as Cu and Ag bonding wires. The main benefits of using Cu bonding wire over Au bonding wire are lower material cost, higher electrical and thermal conductivity that enables smaller diameter Cu bonding wire to carry identical current as an Au bonding wire without overheating, and lower reaction rates between Cu and Al that serve to improve the reliability performance in long periods of high temperature storage conditions. However, the high hardness, easy oxidation, and complex bonding process of Cu bonding wire make it not the best alternative for Au bonding wire. Therefore, Ag bonding wire as a new alternative with potential application comes to the packaging market; it has higher thermal conductivity and lower electric resistivity in comparison with Cu bonding wire, which makes it a good candidate for power electronics, and higher elastic modulus and hardness than Au bonding wire, but lower than Cu bonding wire, which makes it easier to bond. This paper begins with a brief introduction about the developing history of bonding wires. Next, manufacturability and reliability of Au, Cu, and Ag bonding wires are introduced. Furthermore, general comparisons on basic performance and applications between the three types of bonding wires are discussed. In the end, developing trends of bonding wire are provided. Hopefully, this review can be regarded as a useful complement to other reviews on wire bonding technology and applications.
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Background: In September 2021, there was an outbreak of coronavirus disease 2019 (COVID-19) in Xiamen, China. Various non-pharmacological interventions (NPIs) and pharmacological interventions (PIs) have been implemented to prevent and control the spread of the disease. This study aimed to evaluate the effectiveness of various interventions and to identify priorities for the implementation of prevention and control measures. Methods: The data of patients with COVID-19 were collected from 8 to 30 September 2021. A Susceptible-Exposed-Infectious-Recovered (SEIR) dynamics model was developed to fit the data and simulate the effectiveness of interventions (medical treatment, isolation, social distancing, masking, and vaccination) under different scenarios. The effective reproductive number (Reff ) was used to assess the transmissibility and transmission risk. Results: A total of 236 cases of COVID-19 were reported in Xiamen. The epidemic curve was divided into three phases (Reff = 6.8, 1.5, and 0). Notably, the cumulative number of cases was reduced by 99.67% due to the preventive and control measures implemented by the local government. In the effective containment stage, the number of cases could be reduced to 115 by intensifying the implementation of interventions. The total number of cases (TN) could be reduced by 29.66-95.34% when patients voluntarily visit fever clinics. When only two or three of these measures are implemented, the simulated TN may be greater than the actual number. As four measures were taken simultaneously, the TN may be <100, which is 57.63% less than the actual number. The simultaneous implementation of five interventions could rapidly control the transmission and reduce the number of cases to fewer than 25. Conclusion: With the joint efforts of the government and the public, the outbreak was controlled quickly and effectively. Authorities could promptly cut the transmission chain and control the spread of the disease when patients with fever voluntarily went to the hospital. The ultimate effect of controlling the outbreak through only one intervention was not obvious. The combined community control and mask wearing, along with other interventions, could lead to rapid control of the outbreak and ultimately lower the total number of cases. More importantly, this would mitigate the impact of the outbreak on society and socioeconomics.
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COVID-19 , Número Básico de Reprodução , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Surtos de Doenças/prevenção & controle , Humanos , SARS-CoV-2RESUMO
Objective: This study elaborated the natural history parameters of Delta variant, explored the differences in detection cycle thresholds (Ct) among cases. Methods: Natural history parameters were calculated based on the different onset time and exposure time of the cases. Intergenerational relationships between generations of cases were calculated. Differences in Ct values of cases by gender, age, and mode of detection were analyzed statistically to assess the detoxification capacity of cases. Results: The median incubation period was 4 days; the detection time for cases decreased from 25 to 7 h as the outbreak continued. The average generation time (GT), time interval between transmission generations (TG) and serial interval (SI) were 3.6 ± 2.6 days, 1.67 ± 2.11 days and 1.7 ± 3.0 days. Among the Ct values, we found little differences in testing across companies, but there were some differences in the gender of detected genes. The Ct values continuous to decreased with age, but increased when the age was greater than 60. Conclusion: This epidemic was started from aggregation of factories. It is more reasonable to use SI to calculate the effective reproduction number and the time-varying reproduction number. And the analysis of Ct values can improve the positive detection rate and improve prevention and control measures.
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In this study, we employed a dual strategy for parathion organophosphate pesticide (parathion) detection; first, we used a localized surface plasmon resonance (LSPR)-based colorimetric sensor featuring thiol-capped Au NPs, namely cysteine (Cys)@Au NPs, 11-mercaptoundecanoic acid (11-MUA)@Au NPs, and glutathione (GSH)@Au NPs, via acetylcholinesterase (ACHE) and acetylthiocholine (ATCH) enzyme-mediated hydrolysis reactions; second, we developed a color analysis toxicity-sensing app (Toxin APP). Positively charged thiocholine (TCH) molecules, which were continuously generated via hydrolysis, subsequently conjugated with thiol-capped Au NPs, causing Au NP aggregation through electrostatic attractions. The degree of aggregation of the thiol-capped Au NPs was influenced by parathion concentrations in the range 0 to 108 ppt, because parathion acted as an ACHE inhibitor by controlling the amount of TCH generated. Based on the values of LSPR absorbance ratio, the limits of detection (LODs) of three types thiol-capped Au NPs were determined to be 100 ppt using ultraviolet-visible spectroscopy measurements. However, the aggregation efficiency of GSH@Au NPs was lower than that of the others regarding gradual changes in their color and LSPR absorbance band. Furthermore, we designed Toxin APP for color analysis which consists of three modules: processing, database collection, and communication. Toxin APP could on-site and precisely detect the color changes of GSH@Au NPs at parathion concentrations in the ranges of 100 ppt to 1, 10, and 100 ppm and could distinguish between OP and non-OP pesticides (e.g., fipronil) in tap water samples with high sensitivity and selectivity. Moreover, the concentration of residual parathion in real samples (tomato and strawberry) was quantified based on the color changes of GSH@Au NPs detected using Toxin APP. Therefore, the combination of an LSPR-based colorimetric assay and Toxin APP can be a reliable method for the facile and rapid detection of parathion in food and water samples.
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Nanopartículas Metálicas , Aplicativos Móveis , Paration , Praguicidas , Acetilcolinesterase , Colorimetria , Ouro , Praguicidas/análise , Praguicidas/toxicidade , Compostos de Sulfidrila , Ressonância de Plasmônio de SuperfícieRESUMO
Objective: This study uses four COVID-19 outbreaks as examples to calculate and compare merits and demerits, as well as applicational scenarios, of three methods for calculating reproduction numbers. Method: The epidemiological characteristics of the COVID-19 outbreaks are described. Through the definition method, the next-generation matrix-based method, and the epidemic curve and serial interval (SI)-based method, corresponding reproduction numbers were obtained and compared. Results: Reproduction numbers (R eff ), obtained by the definition method of the four regions, are 1.20, 1.14, 1.66, and 1.12. Through the next generation matrix method, in region H R eff = 4.30, 0.44; region P R eff = 6.5, 1.39, 0; region X R eff = 6.82, 1.39, 0; and region Z R eff = 2.99, 0.65. Time-varying reproduction numbers (R t ), which are attained by SI of onset dates, are decreasing with time. Region H reached its highest R t = 2.8 on July 29 and decreased to R t < 1 after August 4; region P reached its highest R t = 5.8 on September 9 and dropped to R t < 1 by September 14; region X had a fluctuation in the R t and R t < 1 after September 22; R t in region Z reached a maximum of 1.8 on September 15 and decreased continuously to R t < 1 on September 19. Conclusion: The reproduction number obtained by the definition method is optimal in the early stage of epidemics with a small number of cases that have clear transmission chains to predict the trend of epidemics accurately. The effective reproduction number R eff , calculated by the next generation matrix, could assess the scale of the epidemic and be used to evaluate the effectiveness of prevention and control measures used in epidemics with a large number of cases. Time-varying reproduction number R t , obtained via epidemic curve and SI, can give a clear picture of the change in transmissibility over time, but the conditions of use are more rigorous, requiring a greater sample size and clear transmission chains to perform the calculation. The rational use of the three methods for reproduction numbers plays a role in the further study of the transmissibility of COVID-19.
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Based on the involvement of nuclear factor-κB inhibitor alpha (NFKIBA) in the NF-κ B pathway, which is closely related to host immunity, we evaluated whether NFKIBA polymorphisms are associated with the disease progression of chronic hepatitis B virus (HBV) infection. We collected blood samples from a total of 212 treatment-naïve patients with chronic HBV infection. NFKBIA polymorphisms were determined by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry. Enzyme-linked immunosorbent assays were employed to quantify the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6(IL-6). Unconditional logistic regression revealed that carriers of the TT genotype at rs2233406 had a greater risk (OR = 5.57, 95% CI = 2.14-14.52) of chronic HBV infection progression. A similar association was observed for the rs2233409 polymorphism, in which the OR for the TT genotype was 4.06 (95% CI = 1.70-9.71) compared to that for the wildtype CC genotype. Mutations at rs2233406 and rs2233409 also impact liver function parameters and cytokine levels. However, null associations were observed between these parameters and rs696 polymorphism. These findings suggest that reduced NFKBIA function leads to activation of the NF-κB pathway, and consequently causes inflammation and liver damage among patients with chronic HBV infection.
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Povo Asiático/genética , Hepatite B Crônica/genética , Inibidor de NF-kappaB alfa/genética , Adulto , Idoso , Progressão da Doença , Feminino , Estudos de Associação Genética , Hepatite B Crônica/patologia , Humanos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único/genética , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
Mannose binding lectin (MBL) plays important role in the innate immunity of human. Mutations in the MBL2 gene can significantly change the serum level of MBL, and consequently alter the susceptibility and progression of infectious disease. However, the association between the MBL2 profile and the HBV mutation and quasispecies complexity has not yet been reported. Our approach includes the study of the MBL2 gene genotype as well as ultra-deep sequencing of the HBV viruses obtained from the plasma of 50 treatment naïve patients with chronic HBV infection. We found that the liver function was better among patients within the high MBL2 group with respect to those within the medium/low MBL2 group. Likewise, the number of mutations in the HBV X gene as well as the viral quasispecies complexity were significantly higher in medium/low MBL2 production group. Nucleotide substitution rates were also higher within the medium/low MBL2 production group in all positions described to have an influence in liver cancer development, except for A1499G. In this work we show that the MBL2 profile may have an impact on the HBV X gene mutations as well as on viral quasispecies complexity.
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Genes Virais , Haplótipos , Vírus da Hepatite B/genética , Hepatite B/imunologia , Lectina de Ligação a Manose/genética , Mutação , Adulto , Idoso , Progressão da Doença , Feminino , Predisposição Genética para Doença , Hepatite B/genética , Humanos , Imunidade Inata , Masculino , Lectina de Ligação a Manose/sangue , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto JovemRESUMO
Long non-coding RNAs are involved with development and progression of cancer, and the advance of microarray technology allows the researchers to investigate the complete expression profile of lncRNA in various kinds of sample. We enrolled 5 male primary HCC cases with chronic HBV infection and the HCC and normal tissues have been obtained during the resection surgery. After total RNA extraction, the lncRNA microarray analysis was conducted to determine the lncRNA and mRNA expression signals. 612 lncRNAs and 1,064 mRNAs were significantly up-regulated in HCC tissue while 656 lncRNAs and 1,532 mRNAs were down-regulated in HCC tissues. Compared with normal tissues, XLOC_007433 (fold change: 12.80) and AC144449.1 (fold change: 27.20) were the most over- and under-expressed lncRNAs in HCC tissues. As for the mRNA, THBS4 (fold change:41.13) and CXCL14 (fold change: 58.03) were the most over- and under-expressed mRNAs in HCC tissues when comparing with their normal counterparts. In total, 4,552 pairs of lncRNA-mRNA were identified and the co-expression network was constructed. Moreover, the gene ontology enrichment analysis showed that the significantly different transcript between HCC and normal tissues were mainly associated with response to wounding, inflammatory response, protein hetrodimerization activity, response to stress which involved with biological process and molecular function. The pathway analysis suggested that the most significant pathways consisted of alcoholism, regulatory RNA pathways and RNA polymerase transcription. Several novel differentially expressed lncRNAs and mRNAs were identified in the present study.
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Carcinoma Hepatocelular/etiologia , Regulação Neoplásica da Expressão Gênica , Hepatite B Crônica/complicações , Neoplasias Hepáticas/etiologia , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Carga TumoralRESUMO
The innate immunity gene mannose-binding lectin2 (MBL2) has played an important role in hepatitis B virus (HBV) infection, and the relationship between MBL2 variants and hepatocellular carcinoma (HCC) risk has not yet been identified. In total, 315 HCC cases and 315 healthy controls were enrolled and blood samples were acquired. High resolution melt analysis (HRM) was employed to genotype 6 polymorphisms in MBL2 gene. Increased HCC risk in carriers of LL genotype of -550 polymorphism with an adjusted OR (AOR) of 1.61 (95%CI = 1.00-2.57) was observed but no significant association detected in HL genotype. Both YX and XX genotype demonstrated a significantly elevated HCC risk in the analysis of -221 polymorphism. The B variants in codon 54 was also significantly associated with elevated HCC risk. HYB was identified as the protective factor of HCC while LXB was significantly associated with increase HCC risk. ELISA technique revealed that the MBL2 protein was significantly reduced in HCC cases. Moreover, both IL-1ß and IL-6 were inversely associated with plasma MBL2 level.The mutations in MBL2 could lead to compromised innate immunity, and possibly lead to elevated HCC risk, and a novel haplotype HXB has been identified with a rate of 12.5%.
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Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Haplótipos , Neoplasias Hepáticas/genética , Lectina de Ligação a Manose/genética , Adulto , Idoso , Povo Asiático/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-6/sangue , Neoplasias Hepáticas/patologia , Modelos Logísticos , Masculino , Lectina de Ligação a Manose/sangue , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
Incidence of hepatocellular carcinoma (HCC) ranked the fifth in male and ninth in the female counterparts, and 50% of incidence HCC cases were occurred in China with high hepatitis B virus (HBV) prevalence. HCC has seriously compromised the health status of general population in China. A case-control study of 314 HCC cases and 346 controls was conducted in Xiamen, which is an epidemic area in China for both hepatitis B infection and HCC. Face-to-face interview was conducted to gather information on demographic characteristics as well as exposure of environmental factors. Commercial enzyme-linked immunosorbent assay kits were used to determine the status of serological markers of HBV infection. Odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Multivariate unconditional logistic regression analysis was applied to evaluate the potential interactions of variables or confounders.As expected, HBV and alcohol intake still are the major risk factors of HCC. Liver disease history and passive smoking are also associated with elevated HCC risk. Indoor air pollution and pesticide exposure have newly identified as risk factors of HCC. Fruit and tea intake can significantly lower the HCC risk.The application of HBV vaccine and reduction on alcohol intake should be further promoted in high-risk population. Fruit and tea can be served as chemoprevention in daily life due to their high accessibility.