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It is important to encourage parental acceptance of children's vaccination against COVID-19 to ensure population immunity and mitigate morbidity and mortality. This study drew upon protection motivation theory (PMT) to explore the factors of parental hesitancy about vaccinating their children. A national online survey was performed in China. A total of 2054 Chinese parents of children aged 6-12 years were included in this study. They reported on measures that assessed hesitancy about children's vaccination against COVID-19, PMT constructs (susceptibility, severity, response efficacy, self-efficacy, and response costs) and sociodemographic characteristics. Chinese parents reported a hesitancy rate of 29.4% for children's vaccination. Parents with higher level education were more likely to hesitate to vaccinate their children against COVID-19. After controlling for parents' and children's demographic variables, logistic regression showed that parents' hesitancy about their children's vaccination increased if parents had lower levels of susceptibility, response efficacy or self-efficacy, as well as higher levels of response costs. In addition, a high educational level can significantly increase the promotive effect of response cost and the protective effect of response efficacy on vaccine hesitancy. In conclusion, our findings suggested that PMT can explain parents' vaccine hesitancy and that education level can modify the effect of copying appraisal, but not threat appraisal, on parental hesitancy. This study will help public health officials send targeted messages to parents to improve the rate of COVID-19 vaccination in children aged 6-12 years and thus reach a higher level of immunity in the population.

Background Gut microbiota (GMB) alteration has been reported to influence the Alzheimer’s disease (AD) pathogenesis through immune, endocrine, and metabolic pathways. This study aims to investigate metabolic output of the dysbiosis of GMB in AD pathogenesis. In this study, the fecal microbiota and metabolome from 21 AD participants and 44 cognitively normal control participants were measured. Untargeted GMB taxa was analyzed through 16S ribosomal RNA gene profiling based on next-generation sequencing and fecal metabolites were quantified by using ultrahigh performance liquid chromatography-mass spectrometry (UPLC-MS). Results Our analysis revealed that AD was characterized by 15 altered gut bacterial genera, of which 46.7% (7/15 general) was significantly associated with a series of metabolite markers. The predicted metabolic profile of altered gut microbial composition included steroid hormone biosynthesis, N-Acyl amino acid metabolism and piperidine metabolism. Moreover, a combination of 2 gut bacterial genera (Faecalibacterium and Pseudomonas) and 4 metabolites (N-Docosahexaenoyl GABA, 19-Oxoandrost-4-ene-3,17-dione, Trigofoenoside F and 22-Angeloylbarringtogenol C) was able to discriminate AD from NC with AUC of 0.955 in these 65 subjects. Conclusions These findings demonstrate that gut microbial alterations and related metabolic output changes may be associated with pathogenesis of AD, and suggest that fecal markers might be used as a non-invasive examination to assist screening and diagnosis of AD.

Background and aims Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC. Methods We analysed three cohorts including 895 HCC patients. TP53 mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression-free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy. Results In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P = .006) and PFS (P = .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P = 8.291 × 10-7 and 2.608 × 10-7 in Cohorts 2 and 3, respectively) and PFS (P = 5.115 × 10-7 and 5.900 × 10-13 in Cohorts 2 and 3, respectively) compared to those without this mutation. Conclusions TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.

To investigate the association between interleukin (IL)-1α (rs1800587), IL-1β (rs1143634) and IL-1 receptor antagonist (RN) variable number tandem repeat polymorphisms, expression levels and lumbar disc disease (LDD).All relevant articles were searched from 4 databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to evaluate the association between IL-1 gene locus polymorphisms (rs1800587 in IL-1α, rs1143634 in IL-1β, variable number tandem repeat in interleukin-1 receptor antagonist) and LDD susceptibility. Statistical analysis was conducted by Review Manager (Revman) 5.31 software (Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark). Furthermore, qRT-PCR and immunohistochemistry were performed to evaluate IL-1α, IL-1β and interleukin-1 receptor antagonist expressions in the normal and degenerated disc.A total of 15 case-control studies (1455 cases and 2362 controls) were included in our meta-analysis. The pooled results suggested that IL-1α rs1800587 polymorphism was associated with an increased risk of LDD in overall population (T vs. C, OR = 1.21, 95% CI = 1.04-1.40, P = .01). The subgroup analysis found a significant association between IL-1β rs1143634 polymorphism and LDD in Asian population (T vs. C, OR = 0.61, 95% CI = 0.39-0.96, P = .03). Results of qRT-PCR and immunohistochemistry demonstrated that expressions of IL-1α and IL-1β were significantly increased in the degenerated disc. (all P.05).IL-1α rs1800587 and IL-1β rs1143634 polymorphisms were significantly associated with LDD in overall population and in Asian population, respectively. The increased expression levels of IL-1α and IL-1β may be the important risk factors for LDD.

Background The control of vaccine hesitancy and the promotion of vaccination are key protective measures against COVID-19. Objective This study assesses the prevalence of vaccine hesitancy and the vaccination rate and examines the association between factors of the health belief model (HBM) and vaccination. Methods A convenience sample of 2531 valid participants from 31 provinces and autonomous regions of mainland China were enrolled in this online survey study from January 1 to 24, 2021. Multivariable logistic regression was used to identify the associations of the vaccination rate and HBM factors with the prevalence of vaccine hesitancy after other covariates were controlled. Results The prevalence of vaccine hesitancy was 44.3% (95% CI 42.3%-46.2%), and the vaccination rate was 10.4% (9.2%-11.6%). The factors that directly promoted vaccination behavior were a lack of vaccine hesitancy (odds ratio [OR] 7.75, 95% CI 5.03-11.93), agreement with recommendations from friends or family for vaccination (OR 3.11, 95% CI 1.75-5.52), and absence of perceived barriers to COVID-19 vaccination (OR 0.51, 95% CI 0.35-0.75). The factors that were directly associated with a higher vaccine hesitancy rate were a high level of perceived barriers (OR 1.63, 95% CI 1.36-1.95) and perceived benefits (OR 0.51, 95% CI 0.32-0.79). A mediating effect of self-efficacy, influenced by perceived barriers (standardized structure coefficient [SSC]=−0.71, P Conclusions It may be possible to increase the vaccination rate by reducing vaccine hesitancy and perceived barriers to vaccination and by encouraging volunteers to advocate for vaccination to their friends and family members. It is also important to reduce vaccine hesitancy by enhancing self-efficacy for vaccination, due to its crucial mediating function.

Haoming Mai,1,&ast; Jiaxuan Chen,1,&ast; Haitao Chen,1,2,&ast; Zhiwei Liu,3,&ast; Guanlin Huang,1 Jialin Wang,1 Qianyi Xiao,4 Weihua Ren,5 Bin Zhou,1 Jinlin Hou,1 Deke Jiang1 1State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China; 3Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; 4School of Public Health, Fudan University, Shanghai, 200032, People’s Republic of China; 5Central Laboratory, First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan Province, 471009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deke Jiang; Jinlin HouState Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaTel +86-20-62786533; +86-20-61641941Email dekejiang17@smu.edu.cn; jlhousmu@163.comIntroduction: Genome-wide association studies identified susceptibility loci in the major histocompatibility complex region for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the causal variants underlying HBV-related HCC pathogenesis remain elusive.Methods: With a total of 1,161 HBV-related HCC cases and 1,353 chronic HBV carriers without HCC, we imputed human leukocyte antigen (HLA) variants based on a Chinese HLA reference panel and evaluated the associations of these variants with the risk of HBV-related HCC. Conditional analyses were used to identify independent signals associated with the risk of HBV-related HCC (P false-discovery rate (FDR) < 0.20). A total of 14,930 variants within the MHC region were genotyped or imputed.Results: We identified two variants, rs114401688 (P = 1.05 × 10− 6, PFDR = 2.43 × 10− 3) and rs115126566 (P = 9.04 × 10− 5, PFDR = 1.77 × 10− 1), that are independently associated with the risk of HBV-related HCC. Single nucleotide polymorphism (SNP) rs114401688 is in linkage disequilibrium with a previously reported SNP rs9275319. In the current study, we found that its association with HCC could be explained by HLA-DQB1&ast;04 and HLA-DRB1&ast;04. SNP rs115126566 is a novel risk variant and may function by regulating transcriptions of HLA-DPA1/DPB1 through enhancer-mediated mechanisms. HLA zygosity analysis showed that homozygosity at HLA-DQB1 gene is suggestively associated with a higher risk of HCC (P = 0.10) and the risk was more pronounced in the older age group (age ≥ 50, P = 0.03).Discussion: Our findings further the understanding of the genetic basis for HBV-related HCC predisposition in chronic HBV carriers.Keywords: fine mapping, susceptibility, MHC, hepatocellular carcinoma, HBV

The current study aims to identify psychosocial factors based on protection motivation theory (PMT) influencing Chinese adults’ willingness to receive the COVID-19 vaccine after the emergency use authorization of the New Coronavirus Inactivated Vaccine in China. A cross-sectional online survey was conducted among Chinese residents aged 18–59 years, and 2528 respondents from 31 provinces and autonomous regions were included in the current study. Based on PMT, threat appraisals and coping appraisals were measured. Hierarchical multiple regressions and multivariate logistic regressions were used to identify the relationships between the PMT constructs and vaccination willingness after other covariates were controlled for. A total of 1411 (55.8%) respondents reported being willing to receive the COVID-19 vaccine. The PMT model explained 26.6% (p &lt, 0.001) of the variance in the vaccine willingness. The coping appraisals, including response efficacy, self-efficacy, and response costs, were significantly correlated with the willingness to receive the COVID-19 vaccine, and response efficacy was the strongest influencing factor (adjusted OR = 2.93, 95% CI: 2.42–3.54). In conclusion, the coping appraisals for vaccination, instead of threat appraisals regarding the pandemic itself, mainly influenced people’s willingness to get vaccinated after the emergency use authorization of the COVID-19 vaccine in China. These findings are helpful for developing education and interventions to promote vaccination willingness and enhance public health outcomes during a pandemic.

Background Cognitive leisure activity, such as reading, playing mahjong or cards and computer use, is common among older adults in China. Previous studies suggest a negative correlation between cognitive leisure activity and cognitive impairment. However, the relationship between cognitive leisure activity and all-cause mortality has rarely been reported. Objectives This study aims to explore the relationships between cognitive leisure activity and all-cause mortality in a community-based older people cohort in China. Methods The current study sample comprised 4003 community residents aged ≥60 y who were enrolled in June 2015, and were followed up every year from 2015 to 2018. Reading, playing mahjong or cards and computer use were measured by questionnaires and summed into a cognitive leisure activity index (CLAI) score. Time-Dependent Cox Regression Model and Kaplan-Meier survival analysis were used to examine the association of cognitive leisure activity with all-cause mortality. Results During the 4-year follow-up of 4003 participants, 208 (5.2%) deaths were registered. Of all participants, 66.8, 26.7, 6.1 and 0.35% reported CLAI scores of 0, 1, 2 and 3, respectively. A strong association was noted between the CLA score and all-cause mortality (adjusted hazard ratio [HR] = 0.72, 95% confidence intervals [CI]: 0.54–0.97, P = 0.028). Stratified analysis suggested that a higher CLAI score was significantly associated with a decreased risk of all-cause mortality mainly among those who were male, aged ≥80 y, cognitively impaired, and not diagnosed with cancer (P Conclusion Cognitive leisure activity was positively associated with reduced risk of death from all cause among the older people in major city of China, which helped promote a comprehensive understanding of health characteristics at advanced ages.

BACKGROUND The control of vaccine hesitancy and the promotion of vaccination are key protective measures against COVID-19. OBJECTIVE This study assesses the prevalence of vaccine hesitancy and the vaccination rate and examines the association between factors of the health belief model (HBM) and vaccination. METHODS A convenience sample of 2531 valid participants from 31 provinces and autonomous regions of mainland China were enrolled in this online survey study from January 1 to 24, 2021. Multivariable logistic regression was used to identify the associations of the vaccination rate and HBM factors with the prevalence of vaccine hesitancy after other covariates were controlled. RESULTS The prevalence of vaccine hesitancy was 44.3% (95% CI 42.3%-46.2%), and the vaccination rate was 10.4% (9.2%-11.6%). The factors that directly promoted vaccination behavior were a lack of vaccine hesitancy (odds ratio [OR] 7.75, 95% CI 5.03-11.93), agreement with recommendations from friends or family for vaccination (OR 3.11, 95% CI 1.75-5.52), and absence of perceived barriers to COVID-19 vaccination (OR 0.51, 95% CI 0.35-0.75). The factors that were directly associated with a higher vaccine hesitancy rate were a high level of perceived barriers (OR 1.63, 95% CI 1.36-1.95) and perceived benefits (OR 0.51, 95% CI 0.32-0.79). A mediating effect of self-efficacy, influenced by perceived barriers (standardized structure coefficient [SSC]=−0.71, PPPPPP CONCLUSIONS It may be possible to increase the vaccination rate by reducing vaccine hesitancy and perceived barriers to vaccination and by encouraging volunteers to advocate for vaccination to their friends and family members. It is also important to reduce vaccine hesitancy by enhancing self-efficacy for vaccination, due to its crucial mediating function.

Children&rsquo, s exposure to secondhand smoke (SHS) is a severe public health problem. There is still a lack of evidence regarding panoramic changes in children&rsquo, s urinary metabolites induced by their involuntary exposure to SHS, and few studies have considered individual differences. This study aims to clarify the SHS-induced changes in urinary metabolites in preschool children by using cross-sectional and longitudinal metabolomics analyses. Urinary metabolites were quantified by using untargeted ultra high-performance liquid chromatography-mass spectrometry (UPLC(c)-MS/MS). Urine cotinine-measured SHS exposure was examined to determine the exposure level. A cross-sectional study including 17 children in a low-exposure group, 17 in a medium-exposure group, and 17 in a high-exposure group was first conducted. Then, a before&ndash, after study in the cohort of children was carried out before and two months after smoking-cessation intervention for family smokers. A total of 43 metabolites were discovered to be related to SHS exposure in children in the cross-sectional analysis (false discovery rate (FDR) corrected p &lt, 0.05, variable importance in the projection (VIP) &gt, 1.0). Only three metabolites were confirmed to be positively associated with children&rsquo, s exposure to SHS (FDR corrected p &lt, 0.05) in a follow-up longitudinal analysis, including kynurenine, tyrosyl-tryptophan, and 1-(3-pyridinyl)-1,4-butanediol, the latter of which belongs to carbonyl compounds, peptides, and pyridines. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that 1-(3-pyridinyl)-1,4-butanediol and kynurenine were significantly enriched in xenobiotic metabolism by cytochrome P450 (p = 0.040) and tryptophan metabolism (p = 0.030), respectively. These findings provide new insights into the pathophysiological mechanism of SHS and indicate the influence of individual differences in SHS-induced changes in urinary metabolites in children.

Additional file1: Figure S1. Kaplan-Meier survival curves of dichotomized individual cognitive leisure activity with survival. (a) playing mahjong or cards. (b) reading. (c) computer use. Table S1. The distribution of education level and individual cognitive leisure activity in Men and Women. Table S2. The distribution of cardiovascular disease, cancer and BMI in PA active and PA inactive. Table S3. Prevalence and death rate of all 8 combinations of cognitive leisure activity behaviours.

Objective: To investigate the association between interleukin (IL)-1α (rs1800587), IL-1β (rs1143634) and IL-1 receptor antagonist (RN) variable number tandem repeat (VNTR) polymorphisms, expression levels and lumbar disc disease (LDD).Methods: All relevant articles were searched from 4 databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI). Odds ratios (OR) with 95 % confidence intervals (CI) were calculated to evaluate the association between IL-1 gene locus polymorphisms (rs1800587 in IL-1α, rs1143634 in IL-1β, VNTR in IL-1RN) and LDD susceptibility. Statistical analysis was conducted by Review Manager (Revman) 5.31 software. Furthermore, qRT-PCR and immunohistochemistry (IHC) were performed to evaluate IL-1α, IL-1β and IL-1RN expressions in the normal and degenerated disc.Results: A total of 15 case-control studies (1455 cases and 2362 controls) were included in our meta-analysis. The pooled results suggested that IL-1α rs1800587 polymorphism was associated with an increased risk of LDD in overall population (T vs. C, OR=1.21, 95%CI=1.04-1.40, P=0.01). The subgroup analysis found a significant association between IL-1β rs1143634 polymorphism and LDD in Asian population (T vs. C, OR=0.61, 95%CI=0.39-0.96, P=0.03). Results of qRT-PCR and IHC demonstrated that expressions of IL-1α and IL-1-β were significantly increased in the degenerated disc. (all PConclusion: IL-1α rs1800587 and IL-1β rs1143634 polymorphisms were significantly associated with LDD in overall population and in Asian population, respectively. The increased expression levels of IL-1α and IL-1β may be the important risk factors for LDD.

Background Mild cognitive impairment (MCI) is an intermediate stage between normal cognition and Alzheimer’s disease (AD). Genome-wide association studies (GWAS) have identified many AD-risk variants and indicated the important role of lipid metabolism pathway in AD progression. This study aimed to investigate the effects of triglyceride (TG) and genetic risk factors on progression from MCI to AD (MCI-AD progression).Methods The current study sample comprised of 305 MCI subjects aged 50 and over who were prospectively followed up for average 4.5 years in a sub-cohort of the Shanghai Aging Study. A consensus diagnosis of incident AD was conducted according to Diagnostic and Statistical Manual of Mental Disorders-IV and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria. Fasting blood samples were obtained at baseline for analyzing serum TG. Single nucleotide polymorphisms (SNPs) genotyping was performed using a MassARRAY system. The effect of TG, genetic variants and their interaction on MCI-AD progression were analyzed using Cox proportional hazards regression model.Results During a mean (±SD) follow-up period of 4.5±1.3 y, 58 subjects developed incident AD. The SNP, rs6859 in the Poliovirus Receptor–Related 2 (PVRL2) gene, was significantly associated with incident AD (false discovery rate (FDR)-adjusted P = 0.018). In multivariate cox model, the PVRL2 rs6859 AG, AA and AG+AA genotypes were associated with significantly increased incident AD, compared with the GG genotype (hazard ratio [HR] = 2.29, P = 0.029, and HR = 2.92, P = 0.013, and HR = 2.47, P =0.012, respectively). In PVRL2 rs6859 AG/AA carriers, higher ln TG was significantly associated with increased risk of incident AD (adjusted HR =2.64, P = 0.034). Ln TG and PVRL2 rs6859 had interactive effect on the MCI-AD progression (P Ln TG × rs6859 = 0.001). Conclusion The present study indicated that PVRL2 rs6859 modified the effect of TG on MCI-AD progression. Precision prevention in MCI population based on genetic information should be considered to avoid progression to AD.

Background The mental activity, such as reading, playing mahjong or cards and computer use, is common among older adults in China. Previous researches suggest a protective role of mental activity against cognitive impairment. However, the relationship between mental activity and all-cause mortality has rarely been reported. Objectives This study aims to explore the effect of mental activity on all-cause mortality in a community-based elderly cohort in China. Methods The current study sample comprised 4003 community residents age ≥ 60 y who were enrolled at June 2015, and were followed up every year from 2015 to 2018. Reading, playing mahjong or cards and computer use were measured by questionnaires and summed into a mental activity index (MAI) score. Cox proportional hazards analysis and Kaplan-Meier survival analysis were used to examined the effect of mental activity on all-cause mortality. Results During 4 y of follow-up of 4003 participants, 208 (5.2%) deaths were registered. Of all participants, 66.8%, 26.7%, 6.1% and 0.35% reported 0, 1, 2 and 3 MAI score, respectively. There was a strong association between the MAI score and all-cause mortality (adjusted hazard ratio [HR] = 0.72, 95% confidence intervals [CI]: 0.54–0.96, P = 0.025). Stratified analysis suggested that higher MAI score was significantly associated with decreased risk of all-cause mortality mainly among those who were male, aged ≥ 80 y, physical inactive, and diagnosed without cancer in past (P

Jiaying Tan,1,* Wenjin Yu,2,* Gang Wu,1 Jun Shen,1 Yong Fang,1 Hechen Zhu,1 Qianyi Xiao,3 Weixia Peng,3 Yukun Lan,3 Ye Gong1 1Department of Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2Department of Pharmacy , Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 3Department of Preventive Medicine and Health Education, School of Public Health, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ye Gong Email gong_ye@fudan.edu.cnBackground: We conducted a real-world analysis of the effectiveness of different antibiotic regimens for bloodstream infections (BSIs) caused by carbapenem-resistant gram-negative bacilli (CR-GNB) in a Chinese population.Methods: A retrospective observational study was conducted between January 2010 and December 2017. Patients with BSIs caused by CR-GNB confirmed by in vitro susceptibility tests were enrolled, and patient medical record data on antimicrobial agents and microbiological and clinical outcomes were extracted.Results: A total of 175 individuals were included; 127 individuals (72.6%) received combination therapy (two or more antibiotics), while 48 individuals (27.4%) received monotherapy (single antibiotic). The all-cause 28-day mortality was 20.0%. Treatment success or presumed success rates were very similar between the monotherapy and combination therapy groups (58.3% versus 59.1%; P = 0.931). Combination therapy had a higher success rate trend than monotherapy in septic shock patients (40.7% versus 18.2%; P = 0.268). Improved therapeutic effects were observed in the active agent-containing group, although the differences were not significant.Conclusion: Combination therapy likely has better therapeutic effects on critical BSIs caused by CR-GNB than monotherapy. Choosing a proper active agent in an antimicrobial regime is relatively crucial to the ultimate treatment outcome.Keywords: bloodstream infection, carbapenem-resistant gram-negative bacilli, antimicrobial regimen, treatment success rate, real-world, Chinese population

Background Generalized Anxiety Disorder (GAD) is a common but urgent mental health problem during disease outbreaks. Resilience buffers against the negative impacts of life stressors on common internalizing psychopathology such as GAD. This study assesses the prevalence of GAD and examines the protective or compensatory effect of resilience against worry factors during the COVID-19 outbreak. Methods A cross-sectional online survey was conducted among Chinese citizens aged ≥18 years from January 31 to February 2, 2020. A total of 4827 participants across 31 provinces and autonomous regions of the mainland of China participated in this study. The Generalized Anxiety Disorder scale (GAD-7), the Connor-Davidson Resilience Scale (CD-RISC), and a self-designed worry questionnaire were used to asses anxiety disorder prevalence, resilience level, and anxiety risk factors. Multivariable logistic regression was used to identify the associations of resilience and worry factors with GAD prevalence after controlling for other covariates. Results The prevalence of anxiety disorder was 22.6% across the 31 areas, and the highest prevalence was 35.4% in Hubei province. After controlling for covariates, the results suggested a higher GAD prevalence among participants who were worried about themselves or family members being infected with COVID-19 (adjusted odds ratio, AOR 3.40, 95%CI 2.43–4.75), worried about difficulty obtaining masks (AOR 1.92, 95%CI 1.47–2.50), worried about difficulty of distinguishing true information (AOR 1.65, 95%CI 1.36–2.02), worried about the prognosis of COVID-19 (AOR 2.41, 95%CI 1.75–3.33), worried about delays in working (AOR 1.71, 95%CI 1.27–.31), or worried about decreased income (AOR 1.45, 95%CI 1.14–1.85) compared with those without such worries. Additionally, those with a higher resilience level had a lower prevalence of GAD (AOR 0.59, 95%CI 0.51–0.70). Resilience also showed a mediating effect, with a negative influence on worry factors and thereby a negative association with GAD prevalence. Conclusion It may be beneficial to promote public mental health during the COVID-19 outbreak through enhancing resilience, which may buffer against adverse psychological effects from worry factors.

Background Recent genome-wide association studies (GWASs) have suggested several susceptibility loci of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by statistical analysis at individual single-nucleotide polymorphisms (SNPs). However, these loci only explain a small fraction of HBV-related HCC heritability. In the present study, we aimed to identify additional susceptibility loci of HBV-related HCC using advanced knowledge-based analysis. Methods We performed knowledge-based analysis (including gene- and gene-set-based association tests) on variant-level association p-values from two existing GWASs of HBV-related HCC. Five different types of gene-sets were collected for the association analysis. A number of SNPs within the gene prioritized by the knowledge-based association tests were selected to replicate genetic associations in an independent sample of 965 cases and 923 controls. Results The gene-based association analysis detected four genes significantly or suggestively associated with HBV-related HCC risk: SLC39A8, GOLGA8M, SMIM31, and WHAMMP2. The gene-set-based association analysis prioritized two promising gene sets for HCC, cell cycle G1/S transition and NOTCH1 intracellular domain regulates transcription. Within the gene sets, three promising candidate genes (CDC45, NCOR1 and KAT2A) were further prioritized for HCC. Among genes of liver-specific expression, multiple genes previously implicated in HCC were also highlighted. However, probably due to small sample size, none of the genes prioritized by the knowledge-based association analyses were successfully replicated by variant-level association test in the independent sample. Conclusions This comprehensive knowledge-based association mining study suggested several promising genes and gene-sets associated with HBV-related HCC risks, which would facilitate follow-up functional studies on the pathogenic mechanism of HCC.

Additional file 1: Supplementary Figure 1. Manhattan plots of p-values of 5,375,073 SNPs obtained by a meta-analysis of two HBV-related HCC GWASs in Chinese populations. Supplementary Figure 2. The quantile-quantile plots of p-values of 5,375,073 SNPs obtained by a meta-analysis of two HBV-related HCC GWASs in Chinese populations. Supplementary Figure 3. Regulatory annotations at gene WHAMMP2. Supplementary Figure 4. Visualization of regulatory annotation at rs17343667 by RegulomeDB. Supplementary Table 1. Genetic association p-values of genes preferentially expressed in liver. Supplementary Table 2. Association p-values of genes frequently intergraded by HBV. Supplementary Table 3. Association p-values of genes with significant association in previous studies. Supplementary Table 4. Association p-values of COSMIC HCC risk genes.

The propagation characteristics of pulsed Gaussian vortex beams are studied in this paper. The propagation equation and intensity distribution of the light beam are derived. The change law of some key parameters, such as the encircled energy radius and the red shift of the Gaussian vortex pulses are quantitatively calculated. It is found that encircled energy radius first increases and then decreases with the increase of the pulse width. When the pulse width is smaller, the space time coupling will affect the energy distribution of the light field. Spectral red shift presents rough exponential decay relationships to the pulse width. When the topological charge is relatively small, the spectral red shift increases quasi-linearly with the topological charge. Then with the increase of the topological charge, the spectral red shift tends to be slow, and finally tends to the asymptotic value.

Background : Recent genome-wide association studies (GWASs) have suggested several susceptibility loci of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by statistical analysis at individual single-nucleotide polymorphisms (SNPs). However, these loci only explain a small fraction of HBV-related HCC heritability. In the present study, we aimed to identify additional susceptibility loci of HBV-related HCC using advanced knowledge-based analysis.Methods: We performed knowledge-based analysis (including gene- and gene-set-based association tests) on variant-level association p-values from two existing GWASs of HBV-related HCC. Five different types of gene-sets were collected for the association analysis. A number of SNPs within the gene prioritized by the knowledge-based association tests were selected to replicate genetic associations in an independent sample of 965 cases and 923 controls.Results: The gene-based association analysis detected four genes significantly or suggestively associated with HBV-related HCC risk: SLC39A8, GOLGA8M, SMIM31, and WHAMMP2. The gene-set-based association analysis prioritized two promising gene set for HCC, cell cycle G1/S transition and NOTCH1 intracellular domain regulates transcription. Within the gene sets, three promising candidate genes (CDC45, NCOR1 and KAT2A) were further prioritized for HCC. Among genes of liver-specific expression, multiple genes previously implicated in HCC were also highlighted. However, probably due to small sample size, none of the genes prioritized by the knowledge-based association analyses are successfully replicated in the independent sample. Conclusions: This comprehensive knowledge-based association mining study suggested several promising genes and gene-sets associated with HBV-related HCC risk. More experiments or larger samples are needed to validate their contribution to the pathogenic mechanism of HCC.

Background: Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies. Methods: We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese community cohort. Conclusion: Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316 participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the log-rank test and Cox regression model. Results: Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio [HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs. non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7 rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However, a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight BMI and AG/AA of ABCA7 rs4147929). Conclusion: ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their risk for incident AD.

The HEY2 (hairy and enhancer of split-related with YRPW motif 2) is reported to play potential roles in tumorigenesis. However, the underlying mechanism in tumorigenesis is remain elusive. The present study aims to investigate the molecular mechanism of biological function of HEY2 in hepatocellular carcinoma (HCC). Dysfunction of the transforming growth factor-beta (TGF-β) pathway plays a critical role in HCC pathogenesis. Here, we identified HEY2 as a suppressor for TGF-β biological response. We demonstrated that HEY2 protein in tumor cytoplasm was up-regulated in HCC. Further, HEY2 overexpression inhibited TGF-β-induced growth arrest of HCC cells and inhibited TGF-β-induced downregulation of c-Myc, both in mRNA and in protein levels. While knockdown of HEY2, by small interfering RNA, was shown to enhance the TGF-β-mediated biological response of HCC cells. Moreover, HEY2 could form complexes with Smad3 and Smad4 and repress Smad3/Smad4 transcriptional activity. In conclusion, our findings indicate a novel role of HEY2 in mediating the TGF-β/Smad signaling pathway in HCC tumorigenesis.

ObjectivesThe aims of this study were to assess the uptake of preventive behaviour during the COVID-19 outbreak and to investigate the factors influencing the uptake of preventive behaviour based on the theory of planned behaviour (TPB）.Design, setting and participantsA cross-sectional online survey was conducted among Chinese residents aged ≥18 years and 4827 participants from 31 provinces and autonomous regions were included in the current study. Uptake of preventive behaviour, attitude towards the spread of COVID-19 and preventive behaviour, subjective norms, perceived behavioural control, demographic characteristics and the information attention and processing mode were measured. Multivariate logistic regressions were used to identify associations between the potential influencing factors and uptake of preventive behaviour.ResultsThere were 2393 (52.8%) respondents reported high uptake of preventive behaviour. Multivariate analyses demonstrated that attitude towards the behaviour, subjective norms and perceived behavioural control were significantly correlated with uptake of preventive behaviour, and perceived behavioural control was the strongest influencing factor (OR=4.09, 95% CI 3.57 to 4.69). Furthermore, systematic information processing mode was positively associated with high uptake of preventive behaviour compared with heuristic information processing mode (OR=2.16, 95% CI 1.67 to 2.81).ConclusionsThese findings are helpful for developing education and interventions to promote high uptake of preventive behaviour and enhance public health outcomes during pandemic.

Single-nucleotide polymorphisms (SNPs) of microRNAs (miRNAs) are considered potential markers of cancer risk and prognosis in various cancers. In the current study, the primary aim is to determine whether the miR-492G>C polymorphism (rs2289030) altered hepatocellular carcinoma (HCC) prognosis. The SNP rs2289030 of miR-492 was genotyped using DNA from blood samples of 362 HCC patients that had undergone surgical resection of a HCC tumor. The associations between overall survival and demographic characteristics, clinical features, and the SNP rs2289030 were estimated using the Cox proportional hazards model. Results showed that patients who carried the CG genotype (P = 0.015, hazard ratio [HR] = 0.704, 95 % confidence interval [CI] 0.530-0.934) and CG+GG genotype (P = 0.011, HR = 0.703, 95 % CI 0.536-0.924) had significantly decreased risk of death compared to those with the CC genotype. Similar results were found in the multivariate analysis adjusted by tumor size and venous invasion. Further stratification analysis indicated that the effect of rs2289030 had more prominence in patients ≤50 years old and that reported ever using alcohol, male gender, a family history of HCC, being HbsAg or alpha fetoprotein (AFP) positive, differentiation I + II, presence of venous invasion or cirrhosis, multiple tumors, and pTNM stage I + II. Results from this study illustrate the potential use of miR-492 rs2289030 as a prognostic marker for HCC patients that have undergone a surgical resection of the tumor.

Background: Recent genome-wide association studies (GWASs) have suggested several susceptibility loci of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by statistical analysis at individual single-nucleotide polymorphisms (SNPs). However, these loci only explain a small fraction of HBV-related HCC heritability. Methods: In the present study, we aimed to identify additional susceptibility loci in two existing HBV-related HCC GWAS datasets using advanced gene- and gene-set-based association tests. Findings: The gene-based association analysis suggested that five genes are associated with HBV-related HCC risk: RNY4, GOLGA8M, LINC01207, WHAMMP2 and SLC39A8 with statistical significance. Through gene-set-based association analysis, we found that the genes in systemic lupus erythematosus pathway may be relevant to development of HBV-related HCC. Three previously reported genes, NAT2, GSTA1 and GSTA2, were also highlighted when genes were stratified in a liver-specific expression set. Furthermore, our analyses suggested that susceptibility loci of HBV-related HCC are unlikely to be enriched in several functional gene sets of HCC defined by our current knowledge. However, our failure to replicate significance at individual SNPs selected from the knowledge-based association analyses in independent cohorts calls for larger replication studies. Interpretation: This comprehensive knowledge-based association mining study suggested several promising genes significantly associated with HBV-related HCC risk, which may shed insights into the pathogenic mechanism of this fatal disorder. Funding Statement: This study was supported by Hong Kong Health and the Medical Research Fund (01121436 and 02132236 to M.X.L.), the National Natural Science Foundation of China (31100895, 81472618 and 81670535 to D.K.J., 81402297 to Q.L.X.), the National Science and Technology Major Project (No. 2018ZX10301202 to D.K.J. and J.H.), the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (No. 2017BT01S131 to D.K.J. and J.H.), the Grant for Recruited Talents to Start Scientific Research from Nanfang Hospital (to D.K.J.), and the Distinguished Youth Scholars Incubation Project of Nanfang Hospital (No. 2017J001 to D.K.J.) Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The study was performed in accordance with guidelines approved by the local ethical committees from all participating centers involved in both the GWAS stage and the replication stage. An informed consent to participate in the study was obtained from each subject in accordance with the declaration of Helsinki principles. All study participants approved the storage of their frozen DNA specimens, for research purposes, in our laboratory.

More than 30 independent single-nucleotide polymorphisms (SNPs) have been associated with Alzheimer's disease (AD) risk by genome-wide association studies (GWAS) in European. We aimed to confirm these SNPs in Chinese Han and investigate the utility of these genetic markers. We randomly divided 459 sporadic AD (SAD) patients and 751 cognitively normal controls into two sets (discovery and testing). Thirty-three SAD risk-associated SNPs were firstly tested in the discovery set. Significant SNPs were used to calculate genetic risk score (GRS) in the testing set. Predictive performance of GRS was evaluated using the area under the receiver operating characteristic curve (AUC). In the discovery set, 6 SNPs were confirmed (P = 7.87 x 10(-11)~0.048), including rs9349407 in CD2AP, rs11218343 in SORL1, rs17125944 in FERMT2, rs6859 in PVRL2, rs157580 and rs2075650 in TOMM40. The first three SNPs were associated with SAD risk independent of APOE genotypes. GRS based on these three SNPs were significantly associated with SAD risk in the independent testing set (P = 0.002). The AUC for discriminating cases from controls was 0.58 for GRS, 0.60 for APOE, and 0.64 for GRS and APOE. Our data demonstrated that GRS based on AD risk-associated SNPs may supplement APOE for better assessing individual risk for AD in Chinese.

A new annular-combination resonator structure adopting the external-injection phase-locking technology is presented theoretically for that the beam quality of stable annular resonator is not satisfying. The phase-locking principle and feasibility are characterized by energy density of injection beam and coupling coefficient. Based on the diffraction theory, output mode of the resonator with phase-locking is deduced and simulated. Results also confirm that injection beam have a good control effect on output mode. The intensity distributions of output beam are studied briefly and indicate that this new resonator which is adaptable to annular gain media can produce high-power laser beam with high quality.

Objective Hepatoma-derived growth factor (HDGF)-related proteins (HRPs) comprise a family of six members and are characterised by a conserved HATH domain. Among the family members, HDGF was the first to be identified as a mitogenic factor and shown to play an important role in hepatocellular carcinoma pathogenesis. The aim of the present study is to examine the relevance of HDGF-related protein-3 (HRP-3), another member of the HRP family in hepatocellular carcinoma (HCC). Design HRP-3 expression in HCC tissues was measured by quantitative reverse transcriptase PCR, western blot and immunohistochemistry analysis. The biological consequences of overexpression and knockdown of HRP-3 in HCC cell lines were studied in vitro and in vivo. Results Expression of HRP-3 mRNA and protein was shown to be highly upregulated in HCC tissues. While knockdown of HRP-3 by small interference RNAs failed to affect anchorage-dependent growth of HCC cells, it inhibited anchorage-independent growth of HCC cells in vitro and xenograft tumour growth in vivo. Further, knockdown of HRP-3 was shown to sensitise HCC cells to anoikis. Moreover, HRP-3 specifically activated the extracellular-signal-regulated kinase (ERK) pathway without affecting c-Jun N-terminal kinase (JNK), p38, AKT and signal transducer and activator of transcription 3 (STAT3). Importantly, inhibition of the ERK pathway diminished HRP-3-mediated protection of HCC cells from anoikis. Finally, knockdown of HRP-3 was shown to enhance apoptosis of HCC cells induced by multiple chemotherapeutic drugs. Conclusion These findings indicate that HRP-3 plays an essential role in HCC pathogenesis and suggest that it may serve as a novel prognostic marker and molecular target for development of drugs for treatment of HCC.

Single nucleotide polymorphisms (SNPs) within microRNAs (miRNAs) are considered potential markers for risk and prognosis of various cancers. In the current study, we aimed to determine whether miR-608 rs4919510 affected hepatocellular carcinoma (HCC) prognosis. We genotyped rs4919510 using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. Associations between rs4919510 and overall survival (OS) and demographic characteristics and clinical features were estimated using the Cox proportional hazards model. Results showed that HCC patients who carried the rs4919510 CC genotype had a significantly longer OS compared to those who carried the GG genotype (P = 0.013, hazard ratio [HR] = 0.600, 95 % confidence interval [CI] 0.402-0.897) and the CG + GG genotype (P = 0.033, HR = 0.681, 95 % CI 0.479-0.970) in univariate analysis. Similar results were obtained in multivariate analysis. Further stratification analysis indicated that rs4919510 was significantly associated with OS in patients who were satisfied with one of the following criteria: male gender, HbsAg-positive, α-fetoprotein (AFP)-positive, tumor size >5 cm, cirrhosis, solitary tumor, I + II pTNM stage, or no tumor capsule. Finally, a significantly higher frequency of rs4919510 CC genotype was observed in patients with cirrhosis (22.9 %, 55/240) than those without cirrhosis (14.0 %, 17/121) (P = 0.047). In conclusion, our results illustrated the potential role of miR-608 rs4919510 as a prognostic marker for HCC patients undergoing surgical resection of the tumor.

The aim of our study was to determine the impact of genetic polymorphisms in the caspase (CASP) genes on prognosis of hepatocellular carcinoma (HCC). We genotyped 7 potentially functional polymorphisms in CASP3, CASP7, CASP8, CASP9, CASP10 genes in 362 HCC patients of receiving surgical resection of HCC tumor. The associations of genotype and haplotype with overall survival (OS) and disease free survival (DFS) were analyzed by using the Cox proportional hazards model. We found that the CASP9 rs4645981 C allele was significantly associated with positive effect on DFS (P = 0.011 and 0.016 for CT+CC vs. TT in univariate and multivariate analysis, respectively), CT genotype was associated with a better OS of HCC than the TT genotype both in univariate and multivariate analysis (P = 0.048 and 0.041, respectively). Moreover, the CASP3 rs2705897 GT genotype showed marginally significant association with decreased OS and DFS, compared with the GG genotype. One haplotype TT/TG in CASP3 (constructed by rs12108497 T>C and rs2705897 T>G) was significantly associated with decreased OS and DFS, compared to the common haplotype TT/TT both in univariate analysis (P = 0.021 and 0.026, respectively) and multivariate analysis (P = 0.025 and 0.030, respectively). The haplotype GT/GT in CASP9 (constructed by rs4645978 A>G and rs4645981 C>T) was significantly associated with decreased DFS both in univariate and multivariate analysis (P = 0.012 and 0.010, respectively). In conclusion, the CASP9 rs4645981 polymorphism, CASP3 and CASP9 haplotypes may be useful prognosis markers for HCC patients with surgical resection of tumor.

Members of the metallothionein (MT) family are short, cysteine-rich proteins involved in metal metabolism and detoxification, suggesting that MT proteins protect cells from damage caused by electrophilic carcinogens and thereby constitute a critical surveillance system against carcinogenesis. However, the roles of MT proteins in human hepatocellular carcinoma (HCC) are not fully understood. We identified a member of the MT family, termed MT1M. MT1M is expressed in various normal tissues with the highest level in the liver. MT1M expression can be induced by heavy metals and protect Escherichia coli from heavy metal toxicity. However, MT1M expression markedly decreased in human HCC specimens. A methylation profiling analysis indicated that the MT1M promoter is methylated in the majority of HCC tumors examined. Moreover, restored expression of MT1M in the HCC cell line Hep3B, which lacks endogenous MT1M expression, suppressed cell growth in vitro and in vivo and augmented apoptosis induced by tumor necrosis factor α. Furthermore, stable expression of MT1M in Hep3B cells blocked tumor necrosis factor α-induced degradation of IκBα and transactivation of NF-κB. We conclude that MT1M is a novel member of the MT family. Frequent downregulation of MT1M in human HCC may contribute to liver tumorigenesis by increasing cellular NF-κB activity.

Far field distributions of Gaussian vortex beams with phase distortion have been studied theoretically, and these studies have provided explanations of the beam behavior to some extent. Based on super-Gaussian incidence by simulation, the beam’s quality has been discussed by investigating the influence of phase distortion with different spatial intensities or spatial frequencies. The tolerance of vortex beams with different topological charges or transporting distances to some different phase distortion have been studied. Results show that phase distortion with stronger peak–valley values or lower spatial frequencies will have a more forceful impact on the quality of beams. Vortex beams with higher topological charges could have more energy-restricting abilities; however, vortex beams with farther distances can keep the quality of beams stable even as they cause energy dispersion.