Publications by authors named "Yongli Yang"

62 Publications

Safety and immunogenicity of an inactivated COVID-19 vaccine, BBIBP-CorV, in people younger than 18 years: a randomised, double-blind, controlled, phase 1/2 trial.

Lancet Infect Dis 2021 Sep 15. Epub 2021 Sep 15.

Beijing Institute of Biological Products, Beijing, China.

Background: Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3-17 years.

Methods: A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3-5 years, 6-12 years, or 13-17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 μg, 4 μg, or 8 μg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn, ChiCTR2000032459, and is ongoing.

Findings: Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 μg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=72, 24 for each age cohort [3-5, 6-12, and 13-17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 μg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=180, 60 for each age cohort [3-5, 6-12, and 13-17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3-5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13-17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3-5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13-17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT against the SARS-CoV-2 virus ranged from 105·3 to 180·2 in the 3-5 years cohort, 84·1 to 168·6 in the 6-12 years cohort, and 88·0 to 155·7 in the 13-17 years cohort on day 28 after the second vaccination; and ranged from 143·5 to 224·4 in the 3-5 years cohort, 127 to 184·8 in the 6-12 years cohort, and 150·7 to 199 in the 13-17 years cohort on day 28 after the third vaccination.

Interpretation: The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3-17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 μg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19.

Funding: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1473-3099(21)00462-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443232PMC
September 2021

Genetic variants in telomerase-associated protein 1 are associated with telomere damage in PAH-exposed workers.

Ecotoxicol Environ Saf 2021 Oct 29;223:112558. Epub 2021 Jul 29.

Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address:

Telomeres are functional complexes at the ends of linear chromosomes, and telomerase aids in their maintenance and replication. Additionally, accumulating evidence suggests that telomerase-associated protein 1 (TEP1) is a component of the telomerase ribonucleoprotein complex and is responsible for catalyzing the addition of new synthetic telomere sequences to chromosome ends. In our previous study, we found that genetic variants of the TERT gene participated in the regulation of telomere length. Exposure to particulate matter, environmental pollutants, oxidative stress, and pesticides is associated with shortening of telomere length. However, it is unknown whether genetic variants in the TEP1 gene may affect telomere length (TL) in polycyclic aromatic hydrocarbon (PAH)-exposed workers. Therefore, we measured the peripheral leukocyte TL and genotyped the polymorphism loci in the TEP1 gene among 544 PAH-exposed workers and 238 healthy controls. Covariance analysis showed that the individuals carrying TEP1 rs1760903 CC and TEP1 rs1760904 TT had longer TL in the control group (P < 0.05). In the generalized linear model, we found that rs1760903 CC was a protective factor against TL shortening, and PAH exposure could promote telomere shortening (P < 0.05). Thus, this study reinforces the roles of environmental factors and genetic variations in telomere damage, and provides a theoretical foundation for the early detection of susceptible populations and the establishment of occupational standards.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112558DOI Listing
October 2021

Spatio-Temporal Analysis of Influenza-Like Illness and Prediction of Incidence in High-Risk Regions in the United States from 2011 to 2020.

Int J Environ Res Public Health 2021 07 2;18(13). Epub 2021 Jul 2.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

About 8% of the Americans contract influenza during an average season according to the Centers for Disease Control and Prevention in the United States. It is necessary to strengthen the early warning for influenza and the prediction of public health. In this study, Spatial autocorrelation analysis and spatial scanning analysis were used to identify the spatiotemporal patterns of influenza-like illness (ILI) prevalence in the United States, during the 2011-2020 transmission seasons. A seasonal autoregressive integrated moving average (SARIMA) model was constructed to predict the influenza incidence of high-risk states. We found the highest incidence of ILI was mainly concentrated in the states of Louisiana, District of Columbia and Virginia. Mississippi was a high-risk state with a higher influenza incidence, and exhibited a high-high cluster with neighboring states. A SARIMA (1, 0, 0) (1, 1, 0) model was suitable for forecasting the ILI incidence of Mississippi. The relative errors between actual values and predicted values indicated that the predicted values matched the actual values well. Influenza is still an important health problem in the United States. The spread of ILI varies by season and geographical region. The peak season of influenza was the winter and spring, and the states with higher influenza rates are concentrated in the southeast. Increased surveillance in high-risk states could help control the spread of the influenza.
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http://dx.doi.org/10.3390/ijerph18137120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297262PMC
July 2021

Benchmark dose analysis for PAHs hydroxyl metabolites in urine based on mitochondrial damage of peripheral blood leucocytes in coke oven workers in China.

Environ Toxicol Pharmacol 2021 Aug 24;86:103675. Epub 2021 May 24.

Department of Occupational Health and Occupational Diseases, College of Public Health, Zhengzhou University, Zhengzhou, China; The Key Laboratory of Nanomedicine and Health Inspection of Zhengzhou, Zhengzhou, China. Electronic address:

Objectives: The aim was to explore the dose-response relationship between occupational polycyclic aromatic hydrocarbons (PAHs) exposure and mitochondrial damage in coke oven plants workers.

Methods: 544 workers and 238 healthy people were recruited. The ultra-high performance liquid chromatography was used to determine the level of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene. The real-time fluorescence quantitative polymerase chain reaction was used to determine the mitochondrial DNA copy number (mtDNAcn). The benchmark dose software was used to analyze the benchmark dose.

Results: The mtDNAcn in the exposure group was lower than that in the control group. The concentrations of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene in the exposure group were higher than those in the control group. There is a dose-response relationship between 1-hydroxypyrene, 3-hydroxyphenanthrene and mitochondrial DNA damage. The benchmark dose lower confidence limit (BMDL) of 1-hydroxypyrene were 0.045, 0.004, and 0.058 pg/μg creatinine in the total, male, and female population, respectively. The BMDL of 3-hydroxyphenanthrene were 5.142, 6.099, and 2.807 pg/μg creatinine in the total, male, and female population, respectively.

Conclusions: The BMDL of 1-hydroxypyrene and 3-hydroxyphenanthrene initially explored can provide a reference to establish occupational exposure biological limits.
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http://dx.doi.org/10.1016/j.etap.2021.103675DOI Listing
August 2021

Cohort study evaluation of New Chinese Diabetes Risk Score: A new non-invasive indicator for predicting metabolic syndrome.

Prim Care Diabetes 2021 May 20. Epub 2021 May 20.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. Electronic address:

Objectives: To investigate the association of the baseline New Chinese Diabetes Risk Score (NCDRS) with metabolic syndrome (MetS) risk and to evaluate the power of the baseline NCDRS to predict MetS based on the rural Chinese cohort study.

Methods: Study participants were classified by baseline quartiles of NCDRS by gender. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of MetS according to different diagnostic criteria. The receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were used to evaluate the power of the baseline NCDRS for predicting MetS according to different diagnostic criteria.

Results: We included 7,133 participants, and 1,651 MetS cases were identified after 6 years follow-up. After adjusting for multivariable confounding factors and with NCDRS quartile 1 as the reference, with quartile 4, the risk of MetS was increased for all participants, men and women: ORs (95% CIs) 4.03 (3.23-5.02), 3.59 (2.56-5.05) and 5.71 (4.23-7.70), respectively. Similar results were found on sensitivity analysis. The baseline NCDRS was a good predictor of MetS for all participants, men and women with MetS defined according to the diagnostic criteria of the Chinese Joint Committee on the Development of Guidelines for the Prevention and Treatment of Dyslipidemia in Adults (JCDCG).

Conclusions: Our study, based on the cohort study, found that the baseline NCDRS was positively associated with risk of MetS. Furthermore, our study might provide suggestions for developing a useful and inexpensive tool for predicting MetS in the Chinese population.
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http://dx.doi.org/10.1016/j.pcd.2021.05.005DOI Listing
May 2021

Birth weight, childhood obesity and risk of hypertension: a Mendelian randomization study.

J Hypertens 2021 Sep;39(9):1876-1883

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, PR China.

Purposes: Observational studies indicate that birth weight and childhood obesity are associated with essential hypertension, but their causal effect on essential hypertension remains unclear. The aim of our study is to elucidate the causal relationship between birth weight, childhood obesity, and essential hypertension by Mendelian randomization (MR) with genetic variants as instrumental variables (IVs).

Methods: We identified IVs based on single nucleotide polymorphisms (SNPs) associated with birth weight (n = 160 295) and childhood obesity (n = 6889, 1509 cases and 5380 controls) from the meta-analysis of a genome-wide association study. Summary level data from the UK Biobank essential hypertension consortium (n = 463 010, 54 358 cases and 408 652 controls) was used to analyze the relationship between IVs and essential hypertension. Two MR analysis methods, two threshold values of selecting IVs, and leave-one-out analysis were used to ensure the robustness of the results.

Results: Genetic predisposition to higher birth weight did not increase the risk of essential hypertension. In contrast, per one standard deviation increase in childhood body mass index was significantly associated with an increased risk of essential hypertension (odds ratio = 1.0075, 95% confidence interval: 1.0035-1.0116) when using seven SNPs that achieved genome-wide significance (P < 5 × 10-8). Sensitivity analysis and MR-Egger regression indicated that the results were robust and not influenced by pleiotropy.

Conclusions: No evidence of an association between birth weight and essential hypertension was found. Childhood obesity, however, showed a causal relationship with the risk of essential hypertension, which was helpful to understand the mechanisms of essential hypertension and develop strategies for its prevention.
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http://dx.doi.org/10.1097/HJH.0000000000002871DOI Listing
September 2021

Identification and Validation of a Tumor Microenvironment-Related Gene Signature for Prognostic Prediction in Advanced-Stage Non-Small-Cell Lung Cancer.

Biomed Res Int 2021 30;2021:8864436. Epub 2021 Mar 30.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

The development of immunotherapy has greatly changed the advanced-stage non-small-cell lung cancer (NSCLC) treatment landscape. The complexity and heterogeneity of tumor microenvironment (TME) lead to discrepant immunotherapy effects among patients at the same pathologic stages. This study is aimed at exploring potential biomarkers of immunotherapy and accurately predicting the prognosis for advanced NSCLC patients. RNA-seq data and clinical information on stage III/IV NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). In TCGA-NSCLC with stage III/IV ( = 192), immune scores and stromal scores were calculated by using the ESTIMATE algorithms. Univariate, LASSO, and multivariate Cox regression analyses were performed to screen prognostic TME-related genes (TMERGs) and constructed a gene signature risk score model. It was validated in external dataset including GSE41271 ( = 91) and GSE81089 ( = 36). Additionally, a nomogram incorporating TMERG signature risk score and clinical characteristics was established. Further, we accessed the proportion of 22 types of tumor-infiltrating immune cells (TIIC) from the CIBERSORT website and analyzed the difference between two risk groups. OS of patients with high immune/stromal scores were higher (log-rank = 0.044/log-rank = 0.048). Multivariate Cox regression identified six prognostic TMERGs, including CD200, CHI3L2, CNTN1, CTSL, FYB1, and SLC52A1. We developed a six-gene risk score model, which was validated as an independent prognostic factor for OS (HR: 3.32, 95% CI: 2.16-5.09). Time-ROC curves showed useful discrimination for TCGA-NSCLC cohort (1-, 2-, and 3-year AUCs were 0.718, 0.761, and 0.750). The predictive robustness was validated in the external dataset. The C-index and 1-, 2-, and 3-year AUCs of nomogram were the largest, which demonstrated the nomogram had the greatest predictive accuracy and effectiveness and could be used for clinical guidance. Besides, the increased infiltration of T cells regulatory (Tregs) and macrophages M2 in the high-risk group suggested that chronic inflammation may reduce survival probability in patients with advanced NSCLC. We conducted a comprehensive analysis of the tumor microenvironment and identified the TMERG signature, which could predict prognosis accurately and provide a reference for the personalized immunotherapy for advanced NSCLC patients.
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http://dx.doi.org/10.1155/2021/8864436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028741PMC
May 2021

Transcriptome-based analysis of the effects of salicylic acid and high light on lipid and astaxanthin accumulation in Haematococcus pluvialis.

Biotechnol Biofuels 2021 Apr 1;14(1):82. Epub 2021 Apr 1.

Shenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Nanshan District, Xueyuan Road No. 1066, Shenzhen, 518060, Guangdong, People's Republic of China.

Background: The unicellular alga Haematococcus pluvialis has achieved considerable interests for its capacity to accumulate large amounts of triacylglycerol and astaxanthin under various environmental stresses. To our knowledge, studies focusing on transcriptome research of H. pluvialis under exogenous hormones together with physical stresses are rare. In the present study, the change patterns at transcriptome level were analyzed to distinguish the multiple defensive systems of astaxanthin and fatty acid metabolism against exogenous salicylic acid and high light (SAHL) stresses.

Results: Based on RNA-seq data, a total of 112,463 unigenes and 61,191 genes were annotated in six databases, including NR, KEGG, Swiss-Prot, PFAM, COG and GO. Analysis of differentially expressed genes (DEGs) in KEGG identified many transcripts that associated with the biosynthesis of primary and secondary metabolites, photosynthesis, and immune system responses. Furthermore, 705 unigenes predicted as putative transcription factors (TFs) were identified, and the most abundant TFs families were likely to be associated with the biosynthesis of astaxanthin and fatty acid in H. pluvialis upon exposure to SAHL stresses. Additionally, majority of the fifteen key genes involved in astaxanthin and fatty acid biosynthesis pathways presented the same expression pattern, resulting in increased accumulation of astaxanthin and fatty acids in single celled H. pluvialis, in which astaxanthin content increased from 0.56 ± 0.05 mg·L at stage Control to 0.89 ± 0.12 mg·L at stage SAHL_48. And positive correlations were observed among these studied genes by Pearson Correlation (PC) analysis, indicating the coordination between astaxanthin and fatty acid biosynthesis. In addition, protein-protein interaction (PPI) network analysis also demonstrated that this coordination might be at transcriptional level.

Conclusion: The results in this study provided valuable information to illustrate the molecular mechanisms of coordinate relations between astaxanthin and fatty acid biosynthesis. And salicylic acid might play a role in self-protection processes of cells, helping adaption of H. pluvialis to high light stress.
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http://dx.doi.org/10.1186/s13068-021-01933-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017637PMC
April 2021

Generation and characterization of a high-affinity chimeric anti-OX40 antibody with potent antitumor activity.

FEBS Lett 2021 06 28;595(11):1587-1603. Epub 2021 Apr 28.

Shanghai ChemPartner Co., Ltd., China.

OX40 is a costimulatory molecule that belongs to the tumor necrosis factor receptor (TNFR) superfamily. OX40 agonist-based combinations are emerging as promising candidates for novel cancer immunotherapy. Clinical trials have shown that OX40 agonist antibodies could lead to better results in cancer patients. Using a hybridoma platform and three different types of immunization strategies, namely recombinant protein, DNA, and overexpressing cells, we identified a chimeric anti-OX40 antibody (mAb035-hIgG1 from DNA immunization) that shows excellent binding specificity, and slightly stronger activation of human memory CD4 T cells and similar potent antitumor activity compared with BMS 986178, an anti-OX40 antibody currently being evaluated for the treatment of solid tumors. This paper further systematically investigates the antigen-specific immune response, the number of binders, epitope bins, and functional activities of antibodies among different immunization strategies. Interestingly, we found that different immunization strategies affect the biological activity of monoclonal antibodies.
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http://dx.doi.org/10.1002/1873-3468.14079DOI Listing
June 2021

Genetic polymorphisms of metabolic enzyme genes associated with leukocyte mitochondrial DNA copy number in PAHs exposure workers.

Cancer Rep (Hoboken) 2021 Aug 31;4(4):e1361. Epub 2021 Mar 31.

Department of Occupational Health and Occupational Diseases, College of Public Health, Zhengzhou University, Zhengzhou, China.

Background: Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure workers has not been fully evaluated.

Aim: The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure.

Methods And Results: We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real-time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1-OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs-exposure [β (95% CI) = -0.420 (-0.469, -0.372), p < .001], male [β (95% CI) = -0.058 (-0.103, -0.012), p = .013], and AA genotype for GSTP1 rs1695 [β (95% CI) = -0.051 (-0.095, -0.008), p = .020].

Conclusion: The individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs.
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http://dx.doi.org/10.1002/cnr2.1361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388165PMC
August 2021

Association of Cycling with Risk of All-Cause and Cardiovascular Disease Mortality: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.

Sports Med 2021 Jul 28;51(7):1439-1448. Epub 2021 Mar 28.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, People's Republic of China.

Background: Cycling has been suggested to be related to risk of all-cause and cardiovascular disease (CVD) mortality. However, a quantitative comprehensive assessment of the dose-response association of cycling with risk of all-cause and CVD mortality has not been reported. We performed a meta-analysis of cohort studies assessing the risk of all-cause and CVD mortality with cycling.

Methods: PubMed and Embase databases were searched for relevant articles published up to December 13, 2019. Random-effects models were used to estimate the summary relative risk (RR) of all-cause and CVD mortality with cycling. Restricted cubic splines were used to evaluate the dose-response association.

Results: We included 9 articles (17 studies) with 478,847 participants and 27,860 cases (22,415 from all-cause mortality and 5445 from CVD mortality) in the meta-analysis. Risk of all-cause mortality was reduced 23% with the highest versus lowest cycling level [RR 0.77, 95% confidence interval (CI) 0.67-0.88], and CVD mortality was reduced 24% (RR 0.76, 95% CI 0.65-0.89). We found a linear association between cycling and all-cause mortality (P = 0.208); the risk was reduced by 9% (RR 0.91, 95% CI 0.86-0.96) with each five metabolic equivalent of task (MET)-h/week increase in cycling. We found an approximately U-shaped association between cycling and CVD mortality (P = 0.034), with the lowest risk at approximately 15 MET-h/week of cycling.

Conclusions: Our findings based on quantitative data suggest that any level of cycling is better than none for all-cause mortality. However, for CVD mortality, one must choose an appropriate level of cycling, with an approximate optimum of 15 MET-h/week (equal to 130 min/week at 6.8 MET).
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http://dx.doi.org/10.1007/s40279-021-01452-7DOI Listing
July 2021

[Protective effects of cordycepin on renal proximal tubular cells injury induced by lipopolysaccharide].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Feb;33(2):203-206

Department of Critical Care Medicine, Hubei NO.3 People's Hospital of Jianghan University, Wuhan 430033, Hubei, China.

Objective: To investigate the protective effect and potential mechanism of cordycepin on renal proximal tubular cells injury induced by lipopolysaccharide (LPS).

Methods: Renal proximal tubular cells NRK-52E were incubated on a cell culture plated at a density of 1×10/mL for experiment, then divided into control group (Ctrl group), LPS group (cells were stimulated with 1 mg/L LPS), 10 μmol/L or 20 μmol/L cordycep in intervention groups (LPS+C 10 group and LPS+C 20 group). Cell viability was measured using cell counting kit-8 (CCK-8) reagent. The level of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining. The protein expressions of inflammatory factors intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-1β (IL-1β), and nuclear factor-κB (NF-κB) were detected by Western blotting.

Results: Compared with the Ctrl group, LPS significantly inhibited NRK-52E cell viability, increased intracellular ROS, and up-regulated the expressions of ICAM-1, VCAM-1, IL-1β and NF-κB. Compared with LPS group, after treated with 10 μmol/L or 20 μmol/L cordycepin, NRK-52E cell viability was significantly increased (Ctrl group as 1: 0.717±0.017, 0.916±0.036 vs. 0.554±0.046) and intracellular ROS level was significantly decreased (Ctrl group as 1: 1.527±0.165, 1.098±0.168 vs. 2.543±0.127), meanwhile the expressions of ICAM-1, VCAM-1, IL-1β and NF-κB were significantly down-regulated [Ctrl group as 1, ICAM-1/GAPDH: 2.364±0.097, 1.561±0.074 vs. 3.101±0.121; VCAM-1/GAPDH: 2.866±0.135, 1.920±0.098 vs. 4.170±0.119; IL-1β/GAPDH: 2.358±0.107, 1.563±0.179 vs. 3.301±0.210; phosphorylation NF-κB p65 (NF-κB p-p65)/GAPDH: 2.559±0.166, 1.596±0.148 vs. 3.183±0.098], the differences were statistically significant (all P < 0.05). Compared with the LPS+C 10 group, the cell activity of LPS+C 20 group was more significant (0.916±0.036 vs. 0.717±0.017, P < 0.01), and the expressions of ICAM-1, VCAM-1, IL-1β, NF-κB were down-regulated more significantly (ICAM-1/GAPDH: 1.561±0.074 vs. 2.364±0.097, VCAM-1/GAPDH: 1.920±0.098 vs. 2.866±0.135, IL-1β/GAPDH: 1.563±0.179 vs. 2.358±0.107, NF-κB p-p65/GAPDH: 1.596±0.148 vs. 2.559±0.166, all P < 0.05).

Conclusions: Cordycepin could significantly increase the survival rate of NRK-52E cells, reduce intracellular ROS level, and inhibit inflammation, and the anti-inflammation effect can be related with NF-κB pathway.
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http://dx.doi.org/10.3760/cma.j.cn121430-20201127-00733DOI Listing
February 2021

Elevated triglyceride-glucose index predicts risk of incident ischaemic stroke: The Rural Chinese cohort study.

Diabetes Metab 2021 07 12;47(4):101246. Epub 2021 Mar 12.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. Electronic address:

Aim: As the association between insulin resistance and ischaemic stroke is conflicting, our study aimed to examine the association between triglyceride-glucose (TyG), a surrogate marker of insulin resistance, and incident ischaemic stroke, and also to further assess the potential effect of modification by several known risk factors of stroke.

Methods: The Rural Chinese Cohort Study enrolled 11,777 participants, aged ≥40 years, who were free of stroke and cardiovascular disease at baseline during 2007-2008, and who were then followed during 2013-2014. TyG was determined using the following formula: Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The relative risk (RR) and 95% confidence interval (CI) of incident ischaemic stroke associated with TyG were estimated using modified Poisson regression models.

Results: During a median follow-up duration of 6 years, 677 new ischaemic stroke cases were identified. After multivariate adjustment, RR (95% CI) values for ischaemic stroke were 1.33 (1.01-1.75), 1.57 (1.17-2.10) and 1.95 (1.34-2.82) in TyG quartile (Q) 2, 3 and 4 groups, respectively, compared with Q1. A significant interaction between TyG index and age for risk of ischaemic stroke (P < 0.001) was also observed. However, no significant interaction was found between TyG index and other potential risk factors of risk for ischaemic stroke, although there were significant positive associations with female, non-smoker, non-drinker, low or moderate physical activity, non-obese and non-type 2 diabetes mellitus groups.

Conclusion: Elevated TyG index is an independent predictor of ischaemic stroke in the general population, and insulin resistance may be positively associated with future stroke risk.
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http://dx.doi.org/10.1016/j.diabet.2021.101246DOI Listing
July 2021

Modulation of gelatinized wheat starch digestion and fermentation profiles by young apple polyphenols in vitro.

Food Funct 2021 Mar 4;12(5):1983-1995. Epub 2021 Feb 4.

College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710119, P. R. China.

To evaluate the effect of young apple polyphenols (YAP) on starch digestion and gut microbiota, complexes of native wheat starch (NWS) with YAP, and their main components chlorogenic acid (CA) and phlorizin (P) were fabricated and gelatinized. Through XRD and FTIR analysis, it was found that the partial crystalline structure of NWS was destroyed during gelatinization, and the addition of P decreased the extent of destruction. Then, the gelatinized starchy samples were subjected to in vitro digestion. The wheat starch (WS)-phenolic compound complexes significantly suppressed the digestion rate and increased the proportion of resistant starch (RS) in WS. Furthermore, the residual starchy components after digestion were fermented by human fecal samples for 24 h. The WS-YAP complex greatly increased the concentration of short-chain fatty acids (SCFAs), especially acetic and propionic acids, and enhanced the growth of health-promoting gut microbiota such as Prevotella. Conclusively, YAP was shown to play a positive role in maintaining blood glucose balance and intestinal health.
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http://dx.doi.org/10.1039/d0fo02752aDOI Listing
March 2021

Estimations of benchmark dose for urinary metabolites of coke oven emissions among workers.

Environ Pollut 2021 Jan 5;273:116434. Epub 2021 Jan 5.

Department of Occupational Health and Occupational Diseases, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China; The Key Laboratory of Nanomedicine and Health Inspection of Zhengzhou, Zhengzhou, 450001, China. Electronic address:

Coke oven emissions (COEs), usually composed of polycyclic aromatic hydrocarbons (PAHs) and so on, may alter the relative telomere length of exposed workers and have been linked with adverse health events. However, the relevant biological exposure limits of COEs exposure has not been evaluated from telomere damage. The purpose of this study is to estimate benchmark dose (BMD) of urinary PAHs metabolites from COEs exposure based on telomere damage with RTL as a biomarker. A total of 544 exposed workers and 238 controls were recruited for participation. High-performance liquid chromatography and qPCR were used to detect concentrations of urinary mono-hydroxylated PAHs and relative telomere length in peripheral blood leukocytes for all subjects. The benchmark dose approach was used to estimate benchmark dose (BMD) and its lower 95% confidence limit (BMDL) of urinary OH-PAHs of COEs exposure based on telomere damage. Our results showed that telomere length in the exposure group (0.75 (0.51, 1.08)) was shorter than that in the control group (1.05 (0.76,1.44))(P < 0.05), and a dose-response relationship was shown between telomere damage and both 1-hydroxypyrene and 3-hydroxyphenanthrene in urine. The BMDL of urinary 1-hydroxypyrene from the optimal model for telomere damage was 1.96, 0.40, and 1.01 (μmol/mol creatinine) for the total, males, and females group, respectively. For 3-hydroxyphenanthrene, the BMDL was 0.94, 0.33, and 0.49 (μmol/mol creatinine) for the total, males, and females. These results contribute to our understanding of telomere damage induced by COEs exposure and provide a reference for setting potential biological exposure limits.
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http://dx.doi.org/10.1016/j.envpol.2021.116434DOI Listing
January 2021

Adherence to antihypertensive medication and cardiovascular disease events in hypertensive patients: a dose-response Meta-analysis of 2,769,700 participants in cohort study.

QJM 2021 Jan 18. Epub 2021 Jan 18.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Background: Recently, many studies have investigated the association between adherence to antihypertensive medication (AHM) and risk of cardiovascular disease (CVD) events for hypertensive patients; however, the results varied by different studies.

Aims: The purpose of our meta-analysis was to explore the comprehensively summarized association between AHM adherence and risk of CVD events in hypertensive patients from cohort studies.

Design: A dose-response meta-analysis.

Methods And Results: We conducted a systematic search in 2 databases (PubMed and Embase) from 1974 to December 15, 2019 to identify English language reports that assessed the association of AHM adherence with risk of CVD events in cohort studies. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated by using a fixed- or random-effects model. Restricted cubic splines were used to evaluate the possible linear or nonlinear association.

Results: We included 16 cohort studies with 2,769,700 participants in the present meta-analysis. The pooled RR of CVD events was 0.66 (95% CI, 0.56-0.78, I2 =98.6%) for the highest versus lowest AHM adherence categories. We found a linear dose-response association of AHM adherence and CVD events (Pnonlinearity =0.887), each 20% increase in AHM adherence was associated with a 13% reduced risk of CVD events (RR 0.87, 95% CI 0.83-0.92, I2 =98.2%) in hypertensive patients.

Conclusion: High AHM adherence has a protective effect on CVD events for hypertensive patients, and improving medication adherence may provide long-term CVD benefits.
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http://dx.doi.org/10.1093/qjmed/hcaa349DOI Listing
January 2021

Identification and validation of an immune-related gene signature predictive of overall survival in colon cancer.

Aging (Albany NY) 2020 12 19;12(24):26095-26120. Epub 2020 Dec 19.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.

The heterogeneity and complexity of tumor-immune microenvironments lead to diverse immunotherapy effects among colon cancer patients. It is crucial to identify immune microenvironment-related biomarkers and construct prognostic risk models. In this study, the immune and stromal scores of 415 cases from TCGA were calculated using the ESTIMATE algorithm. AXIN2, CCL22, CLEC10A, CRIP2, RUNX3, and TRPM5 were screened and established a prognostic immune-related gene (IRG) signature using by univariate, LASSO, and multivariate Cox regression models. The predicted performance of IRG signature was external validated by GSE39582 (n=519). Stratified survival analysis showed IRG signature was an effective predictor of survival in patients with different clinical characteristics. The protein expression level of six genes was validated by immunohistochemistry analysis. Difference analysis indicated the mutation rate, immune cell of resting NK cells and regulatory T cells infiltration and four immune checkpoints of PD-1, PD-L1, LAG3 and VSIR expression levels in the high-risk group were significantly higher than those in the low-risk group. A nomogram incorporating the gene signatures and clinical factors was demonstrated had a good accuracy (1-, 3-, and 5-year AUC= 0.799, 0.791, 0.738). Our study identified a novel IRG signature, which may provide some references for the clinical precision immunotherapy of patients.
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http://dx.doi.org/10.18632/aging.202317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803520PMC
December 2020

A prediction model for outcome in patients with HBV-ACLF based on predisposition, injury, response and organ failure.

Sci Rep 2020 11 19;10(1):20176. Epub 2020 Nov 19.

Medical School of Chinese PLA, Beijing, China.

We aimed to develop a prediction model based on the PIRO concept (Predisposition, Injury, Response and Organ failure) for patients with Hepatitis B Virus (HBV) related acute-on-chronic liver failure (ACLF). 774 patients with HBV related ACLF defined in the CANONIC study were analyzed according to PIRO components. Variables associated with mortality were selected into the prediction model. Based on the regression coefficients, a score for each PIRO component was developed, and a classification and regression tree was used to stratify patients into different nodes. The prediction model was then validated using an independent cohort (n = 155). Factors significantly associated with 90-day mortality were: P: age, gender and ACLF type; I: drug, infection, surgery, and variceal bleeding; R: systemic inflammatory response syndrome (SIRS), spontaneous bacteria peritonitis (SBP), and pneumonia; and O: the CLIF consortium organ failure score (CLIF-C OFs). The areas under the receiver operating characteristics curve (95% confidence interval) for the combined PIRO model for 90-day mortality were 0.77 (0.73-0.80). Based on the scores for each of the PIRO components and the cut-offs estimated from the classification and regression tree, patients were stratified into different nodes with different estimated death probability. Based on the PIRO concept, a new prediction model was developed for patients with HBV related ACLF, allowing stratification into different clusters using the different scores obtained in each PIRO component. The proposed model will likely help to stratify patients at different risk, defining individual management plans, assessing criteria for specific therapies, and predicting outcomes.
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http://dx.doi.org/10.1038/s41598-020-77235-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677318PMC
November 2020

Association between genetic polymorphisms of telomere pathway genes and hydrogen peroxide level in omethoate exposure workers.

Environ Toxicol Pharmacol 2021 Feb 5;82:103541. Epub 2020 Nov 5.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China. Electronic address:

Objective: The aim of this study was to explore the association between genetic variations in telomere pathway genes and the level of hydrogen peroxide (HO) in omethoate exposure workers.

Methods: A total of 180 omethoate exposure workers and 115 healthy controls were recruited. The level of HO in plasma was determined with molybdenic acid colorimetry. Polymerase chain reaction and restriction fragment length was used to detect polymorphisms in POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242, and TERT rs2736098.

Results: The level of HO in exposure group (4.26 ± 0.71) was significantly higher than that in control group (3.29 ± 0.46). Generalized linear models indicated that risk factors for the increase HO level were exposure [β(95 % CI) = 0.951 (0.806, 1.096), P < 0.001] and AA + AT genotype in POT1 rs034794 [β(95 % CI) = 0.397 (0.049, 0.745), P = 0.025].

Conclusion: The increase HO level was associated with omethoate exposure and AA + AT genotypes in POT1 gene rs1034794. It provided a new idea that polymorphisms in telomere pathway genes may indirectly regulate telomere length by influencing oxidative stress.
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http://dx.doi.org/10.1016/j.etap.2020.103541DOI Listing
February 2021

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial.

Lancet Infect Dis 2021 01 15;21(1):39-51. Epub 2020 Oct 15.

Chinese Center for Disease Control and Prevention, Beijing, China.

Background: The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. We aimed to assess the safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate, BBIBP-CorV, in humans.

Methods: We did a randomised, double-blind, placebo-controlled, phase 1/2 trial at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province, China. In phase 1, healthy people aged 18-80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2 at the time of screening, were separated into two age groups (18-59 years and ≥60 years) and randomly assigned to receive vaccine or placebo in a two-dose schedule of 2 μg, 4 μg, or 8 μg on days 0 and 28. In phase 2, healthy adults (aged 18-59 years) were randomly assigned (1:1:1:1) to receive vaccine or placebo on a single-dose schedule of 8 μg on day 0 or on a two-dose schedule of 4 μg on days 0 and 14, 0 and 21, or 0 and 28. Participants within each cohort were randomly assigned by stratified block randomisation (block size eight) and allocated (3:1) to receive vaccine or placebo. Group allocation was concealed from participants, investigators, and outcome assessors. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity, assessed as the neutralising antibody responses against infectious SARS-CoV-2. This study is registered with www.chictr.org.cn, ChiCTR2000032459.

Findings: In phase 1, 192 participants were enrolled (mean age 53·7 years [SD 15·6]) and were randomly assigned to receive vaccine (2 μg [n=24], 4 μg [n=24], or 8 μg [n=24] for both age groups [18-59 years and ≥60 years]) or placebo (n=24). At least one adverse reaction was reported within the first 7 days of inoculation in 42 (29%) of 144 vaccine recipients. The most common systematic adverse reaction was fever (18-59 years, one [4%] in the 2 μg group, one [4%] in the 4 μg group, and two [8%] in the 8 μg group; ≥60 years, one [4%] in the 8 μg group). All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination. Neutralising antibody geometric mean titres were higher at day 42 in the group aged 18-59 years (87·7 [95% CI 64·9-118·6], 2 μg group; 211·2 [158·9-280·6], 4 μg group; and 228·7 [186·1-281·1], 8 μg group) and the group aged 60 years and older (80·7 [65·4-99·6], 2 μg group; 131·5 [108·2-159·7], 4 μg group; and 170·87 [133·0-219·5], 8 μg group) compared with the placebo group (2·0 [2·0-2·0]). In phase 2, 448 participants were enrolled (mean age 41·7 years [SD 9·9]) and were randomly assigned to receive the vaccine (8 μg on day 0 [n=84] or 4 μg on days 0 and 14 [n=84], days 0 and 21 [n=84], or days 0 and 28 [n=84]) or placebo on the same schedules (n=112). At least one adverse reaction within the first 7 days was reported in 76 (23%) of 336 vaccine recipients (33 [39%], 8 μg day 0; 18 [21%], 4 μg days 0 and 14; 15 [18%], 4 μg days 0 and 21; and ten [12%], 4 μg days 0 and 28). One placebo recipient in the 4 μg days 0 and 21 group reported grade 3 fever, but was self-limited and recovered. All other adverse reactions were mild or moderate in severity. The most common systematic adverse reaction was fever (one [1%], 8 μg day 0; one [1%], 4 μg days 0 and 14; three [4%], 4 μg days 0 and 21; two [2%], 4 μg days 0 and 28). The vaccine-elicited neutralising antibody titres on day 28 were significantly greater in the 4 μg days 0 and 14 (169·5, 95% CI 132·2-217·1), days 0 and 21 (282·7, 221·2-361·4), and days 0 and 28 (218·0, 181·8-261·3) schedules than the 8 μg day 0 schedule (14·7, 11·6-18·8; all p<0·001).

Interpretation: The inactivated SARS-CoV-2 vaccine, BBIBP-CorV, is safe and well tolerated at all tested doses in two age groups. Humoral responses against SARS-CoV-2 were induced in all vaccine recipients on day 42. Two-dose immunisation with 4 μg vaccine on days 0 and 21 or days 0 and 28 achieved higher neutralising antibody titres than the single 8 μg dose or 4 μg dose on days 0 and 14.

Funding: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.
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http://dx.doi.org/10.1016/S1473-3099(20)30831-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561304PMC
January 2021

Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials.

JAMA 2020 09;324(10):951-960

National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co Ltd, Wuhan, Hubei, China.

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed.

Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China.

Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 μg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 μg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]).

Design, Setting, And Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020.

Main Outcomes And Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups.

Conclusions And Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials.

Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.
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http://dx.doi.org/10.1001/jama.2020.15543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426884PMC
September 2020

Safety and immunogenicity of an alum-adjuvanted whole-virion H7N9 influenza vaccine: a randomized, blinded, clinical trial.

Clin Microbiol Infect 2020 Jul 29. Epub 2020 Jul 29.

Henan Province Centre for Disease Control and Prevention, Centre of Vaccine Clinical Research, China. Electronic address:

Objectives: A case of H7N9 influenza virus infection was first identified in China in 2013. This virus is considered to have high pandemic potential. Here we developed an H7N9 influenza vaccine containing an aluminium adjuvant and evaluated the safety and immunogenicity of the vaccine.

Methods: From October 2017 through August 2018 we conducted a randomized, double-blinded, single-centre phase I clinical trial in China among 360 participants aged ≥12 years. All participants received two doses of the vaccine (7.5, 15 or 30 μg haemagglutinin antigen) or placebo at an interval of 21 days. Adverse event data were collected for 30 days after vaccination. Serum samples were collected on days 0, 21 and 42 for the haemagglutinin inhibition (HI) antibody assay.

Results: A total of 347 participants (347/360, 96.4%) completed the study. The proportions of vaccine-related adverse events after one injection were 56.7% (34/60) in the 7.5-μg group, 86.7% (52/60) in the 15-μg group and 86.7% (52/60) in the 30-μg group. The proportions of adverse events after two injections were less than those reported after the first dose. None of the serious adverse events were related to the vaccine. After receiving two doses of the 7.5-μg vaccine, the proportion of participants achieving an HI titre of ≥40 was 98.2% (55/56, 95%CI 72.3~100.0%), with a geometric mean titre (GMT) of 192.6 (95%CI 162.9~227.8).

Conclusions: The alum-adjuvanted H7N9 whole-virion inactivated vaccine was safe and strongly immunogenic in a population aged ≥12 years.
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http://dx.doi.org/10.1016/j.cmi.2020.07.033DOI Listing
July 2020

Benchmark dose estimation for coke oven emissions based on oxidative damage in Chinese exposed workers.

Ecotoxicol Environ Saf 2020 Oct 2;202:110889. Epub 2020 Jul 2.

Department of Occupational Health and Occupational Diseases, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China; The Key Laboratory of Nanomedicine and Health Inspection of Zhengzhou, Zhengzhou, 450001, China. Electronic address:

Coke oven emissions (COEs) can cause oxidative stress of the body, which in turn induces the occupational lung disease and also increases the risk of other diseases. COEs are the major occupational hazard factors for coke oven workers. The aim of the study is to explore the influences of COEs exposure on oxidative damage and estimate the benchmark dose (BMD) of COEs. A group of 542 workers exposed to COEs and 237 healthy controls from the same city were recruited in this study. The corresponding measuring kits were used to determine the plasma biomarkers of oxidative damage level. Generalized linear models and trend tests were used to analyze the relationship between COEs exposure and biomarkers. EPA Benchmark Dose Software was performed to calculate BMD and the lower confidence limit of the benchmark dose (BMDL) of COEs exposure. A significant association was observed between COEs exposure and oxidative damage with T-AOC as a biomarker. The BMD of COEs exposure were 2.83 mg/m and 1.39 mg/m for males and females, respectively, and the corresponding BMDL were 1.47 mg/m and 0.75 mg/m, respectively. Our results suggested that the exposure level of COEs below the current national occupational exposure limits (OELs) would induce oxidative damage, and the OEL of COEs based on the T-AOC damage was suggested at 0.03 mg/m in this study.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643142PMC
October 2020

Identification of 67 Pleiotropic Genes Associated With Seven Autoimmune/Autoinflammatory Diseases Using Multivariate Statistical Analysis.

Front Immunol 2020 3;11:30. Epub 2020 Feb 3.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.

Although genome-wide association studies (GWAS) have a dramatic impact on susceptibility locus discovery, this univariate approach has limitations in detecting complex genotype-phenotype correlations. Multivariate analysis is essential to identify shared genetic risk factors acting through common biological mechanisms of autoimmune/autoinflammatory diseases. In this study, GWAS summary statistics, including 41,274 single nucleotide polymorphisms (SNPs) located in 11,516 gene regions, were analyzed to identify shared variants of seven autoimmune/autoinflammatory diseases using the metaCCA method. Gene-based association analysis was used to refine the pleiotropic genes. In addition, GO term enrichment analysis and protein-protein interaction network analysis were applied to explore the potential biological functions of the identified genes. A total of 4,962 SNPs ( < 1.21 × 10) and 1,044 pleotropic genes ( < 4.34 × 10) were identified by metaCCA analysis. By screening the results of gene-based -values, we identified the existence of 27 confirmed pleiotropic genes and highlighted 40 novel pleiotropic genes that achieved statistical significance in the metaCCA analysis and were also associated with at least one autoimmune/autoinflammatory in the VEGAS2 analysis. Using the metaCCA method, we identified novel variants associated with complex diseases incorporating different GWAS datasets. Our analysis may provide insights for the development of common therapeutic approaches for autoimmune/autoinflammatory diseases based on the pleiotropic genes and common mechanisms identified.
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http://dx.doi.org/10.3389/fimmu.2020.00030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008725PMC
February 2021

Effect of 1 rs3863242 polymorphism on telomere length in omethoate-exposed workers.

J Environ Sci Health B 2020 20;55(6):525-529. Epub 2020 Feb 20.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.

Telomere length was found to be associated with omethoate exposure and polymorphisms in certain genes among occupational workers. However, whether the polymorphisms in telomere-binding protein genes influence telomere length remains unclear. To explore the correlation between telomere length and polymorphisms in telomere-binding protein genes, telomere length in peripheral blood leukocytes was determined by real-time quantitative polymerase chain reaction in 180 omethoate-exposed workers and 115 healthy controls. Polymorphisms in 10 pairs of alleles were detected using flight mass spectrometry or polymerase chain reaction-restriction fragment length polymorphism technique. The results showed that individuals with GG genotype in 1 rs3863242 had longer telomere lengths than those with AG + AA genotype in the control group ( = 0.005). The multiple regression analysis suggested that both omethoate exposure ( = 0.526,  < 0.001) and 1 rs3863242 GG ( = 0.220,  = 0.002) were related to a longer telomere length. In conclusion, GG genotype in 1 rs3863242 is linked to prolongation of telomere length, and individuals with GG genotype are recommended to strengthen health protection in a Chinese occupational omethoate-exposed population.
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http://dx.doi.org/10.1080/03601234.2020.1728167DOI Listing
September 2020

Dose-related telomere damage associated with the genetic polymorphisms of cGAS/STING signaling pathway in the workers exposed by PAHs.

Environ Pollut 2020 May 21;260:113995. Epub 2020 Jan 21.

Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China. Electronic address:

Telomeres are located at the end of eukaryotic chromosomes and vulnerable to exogenous chemical compounds. Exposure to coke oven emissions (COEs) leads to a dose-related telomere damage, and such chromosomal damage might trigger the cGAS/STING signaling pathway which plays an important role in immune surveillance. However, the relationship between the genetic variations in the cGAS/STING signaling pathway and telomere damage in the COEs-exposure workers has not been investigated. Therefore, we recruited 544 coke oven workers and 238 healthy control participants, and determined the level of COEs exposure, concentration of urinary 1-hydroxypyrene (1-OHPYR), genetic polymorphisms and telomere length. The results showed that the telomere length significantly decreased from the control-to high-exposure groups as defined by the external exposure level (P < 0.05). The results also indicated that STING rs7447927 CC, cGAS rs34413328 AA, and cGAS rs610913 AA could inhibit telomere shortening in the exposure group (P < 0.05), and cGAS rs34413328, urine 1-OHPYR and cumulative exposure dose (CED) had a significant association with telomere length by generalized linear model. In conclusion, telomere shortening was a combined consequence of short-term exposure, long-term exposure, and genetic variations among the COEs-exposure workers.
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http://dx.doi.org/10.1016/j.envpol.2020.113995DOI Listing
May 2020

Identification of Three Differentially Expressed miRNAs as Potential Biomarkers for Lung Adenocarcinoma Prognosis.

Comb Chem High Throughput Screen 2020 ;23(2):148-156

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.

Objective: The aim of this study areto screen MicroRNAs (miRNAs) related to the prognosis of lung adenocarcinoma (LUAD) and to explore the possible molecular mechanisms.

Methods: The data for a total of 535 patients with LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database. The miRNAs for LUAD prognosis were screened by both Cox risk proportional regression model and Last Absolute Shrinkage and Selection Operator (LASSO) regression model. The performances of the models were verified by time-dependent Receiver Operating Characteristic (ROC) curve. The possible biological processes linked to the miRNAs' target genes were analyzed by Gene Ontology (GO), Kyoto gene and genome encyclopedia (KEGG).

Results: Among 127 differentially expressed miRNAs identified from the screening analysis, there are 111 up-regulated and 16 down-regulated miRNAs. Three of them, hsa-miR-1293, hsa-miR-490 and hsa-miR- 5571, were also significantly associated with the survival of the LUAD patients. The targets of the three miRNAs are significantly enriched in systemic lupus erythematosus pathways.

Conclusion: Hsa-miR-1293, hsa-miR-490 and hsa-miR-5571 can be potentially used as novel biomarkers for the prognosis prediction of LUAD.
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http://dx.doi.org/10.2174/1386207323666200124123103DOI Listing
April 2021

Polycyclic aromatic hydrocarbon exposure, miRNA genetic variations, and associated leukocyte mitochondrial DNA copy number: A cross-sectional study in China.

Chemosphere 2020 May 28;246:125773. Epub 2019 Dec 28.

Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China. Electronic address:

Mitochondria DNA was preferentially attacked by the exogenous carcinogens including polycyclic aromatic hydrocarbons (PAHs) relative to nuclear DNA, and nuclear gene variants may account for variability in the mitochondrial DNA copy number (mtDNAcn). However, it remains unclear whether miRNA genetic variations are associated with mitochondrial DNA damage in the PAH-exposed workers. Therefore, we measured the leukocyte mtDNAcn, urinary 1-hydroxypyrene (1-OHPYR), environmental PAH exposure, and miRNA genetic polymorphisms among 544 coke oven workers and 238 healthy control participants. We found that the mtDNAcn in the exposure group (0.60 ± 0.29) was significantly lower than that in the control group (1.03 ± 0.31) (t = 18.931, P < 0.001). Spearman correlation analysis showed that the peripheral blood leukocyte mtDNAcn had significantly negative correlations with the levels of 1-OHPYR and environmental PAH exposure (P < 0.001). Covariance analysis indicated that miR-210 rs11246190 AA, miR-210 rs7395206 CC, and miR-126 rs2297538 GG probably promoted a decrease in leukocyte mtDNAcn in the exposure or control groups (P < 0.05). In generalized linear model, miR-210 rs11246190 GG was a protective factor of mtDNAcn, and environmental PAH exposure was the risk factor of the mtDNAcn. In conclusion, the decrease of leukocyte mtDNAcn is the result of a combination of environmental and genetic factors.
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http://dx.doi.org/10.1016/j.chemosphere.2019.125773DOI Listing
May 2020

Effects of polycyclic aromatic hydrocarbon exposure and miRNA variations on peripheral blood leukocyte DNA telomere length: A cross-sectional study in Henan Province, China.

Sci Total Environ 2020 Feb 18;703:135600. Epub 2019 Nov 18.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address:

Telomeres play a major role in human aging and disease, especially in most cancers. Telomere length was shortened in workers exposed to polycyclic aromatic hydrocarbons (PAHs) and influenced by individual genetic variations in telomere-binding proteins. MicroRNAs (miRNAs) can affect the progress of messenger RNA (mRNA) transcription; however, whether polymorphisms in miRNA can act on the telomere length is still unknown. Therefore, we aimed to explore the relationships between telomere damage and genetic polymorphisms in miRNA or environmental exposure. A total of 544 coke oven workers and 238 healthy controls were recruited. After collecting peripheral blood and extracting the genomic DNA of the study subjects, the telomere length (TL) in their leucocytes was detected by a real-time quantitative polymerase chain reaction (PCR), and polymorphisms in miRNAs were genotyped using the flight mass spectrometry technique. The concentrations of the four urine OH-PAHs were determined by high performance liquid chromatography (HPLC), and the Soxhlet extraction method was used to detect the concentration of coke oven emissions (COEs) in the air. We found that the peripheral blood leucocyte DNA TL was significantly shorter in the exposure group (0.75; 0.51, 1.08) than that in the control group (1.05; 0.76, 1.44) (Z = 7.692, P < 0.001). The total cumulative exposure dose (CED), 1-hydroxypyrene, 2-hydroxynaphthalene, and 3-hydroxyphenanthrene were significantly negatively correlated with TL (r = -0.307, P < 0.001; r = -0.212, P < 0.001; r = -0.110, P = 0.025; r = -0.251, P < 0.001, respectively). MiR-145 rs353291 GG, miR-30a rs2222722 CT/CC, and miR-197 rs1889470 AA could protect the telomere end in the exposed workers (P < 0.05). The interaction between miR-197 rs1889470 and the CED had an effect on TL (β = 0.066, P = 0.034). This is the first study to evaluate gene-environmental interactions for miRNA polymorphisms and PAH exposure in coke oven workers.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135600DOI Listing
February 2020

Diagnostic Value of Plasma MicroRNAs for Lung Cancer Using Support Vector Machine Model.

J Cancer 2019 28;10(21):5090-5098. Epub 2019 Aug 28.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.

: Small single-stranded non-coding RNAs (miRNAs) play an important role in carcinogenesis through degrading target mRNAs. However, the diagnostic value of miRNAs was not explored in lung cancers. In this study, a support-vector-machine (SVM) model for diagnosis of lung cancer was established based on plasma miRNAs biomarkers, clinical symptoms and epidemiology material. : The expressions of plasma miRNA were examined with SYBR Green-based quantitative real-time PCR. : We identified that the expressions of 10 plasma miRNAs (miR-21, miR-20a, miR-210, miR-145, miR-126, miR-223, miR-197, miR-30a, miR-30d, miR-25), smoking status, fever, cough, chest pain or tightness, bloody phlegm, haemoptysis, were significantly different between lung cancer and control groups (<0.05). The accuracies of the combined SVM, miRNAs SVM, symptom SVM, combined Fisher, miRNAs Fisher and symptom Fisher were 96.34%, 80.49%, 84.15%, 84.15%, 75.61%, and 80.49%, respectively; AUC of these six model were 0.976, 0.841, 0.838, 0.865, 0.750, and 0.801, respectively. The accuracy and AUC of combined SVM were higher than the other 5 models (<0.05). : Our findings indicate that SVM model based on plasma miRNAs biomarkers may serve as a novel, accurate, noninvasive method for auxiliary diagnosis of lung cancer.
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http://dx.doi.org/10.7150/jca.30528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775617PMC
August 2019
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