ETCM v2.0: An update with comprehensive resource and rich annotations for traditional Chinese medicine

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

Heritability of tea drinking and its relationship with cigarette smoking in the Chinese male adult twins.

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.

Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study.

Aim: Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. Materials & methods: In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Results: Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. Conclusion: The hypermethylation of cg07326074, located in the tumor-promoting gene C16orf59, was associated with alcohol consumption.

A population-based seroprevalence survey of severe acute respiratory syndrome coronavirus 2 infection in Beijing, China

BACKGOUNDThe spread of Coronavirus Disease 2019 (COVID-19) had been controlled in China. The seroprevalence of COVID-19 in Beijing has not been evaluated. METHODSIn April, residents in Beijing were randomly enrolled. Blood samples were collected and antibodies to SARS- CoV-2 were tested by two colloidal gold kits. All colloidal gold positive serums were then tested by Micro- neutralization assay. RESULTSNone of 2,184 residents participated was tested positive by micro-neutralization assay. The seroprevalence of COVID-19 in Beijing was estimated < 0.17%. CONCLUSIONSThe seroprevalence of COVID-19 was low in April suggesting that community-wide spread was prevented in Beijing.

Cross-neutralization antibodies against SARS-CoV-2 and RBD mutations from convalescent patient antibody libraries

The emergence of coronavirus disease 2019 (COVID-19) pandemic led to an urgent need to develop therapeutic interventions. Among them, neutralizing antibodies play crucial roles for preventing viral infections and contribute to resolution of infection. Here, we describe the generation of antibody libraries from 17 different COVID-19 recovered patients and screening of neutralizing antibodies to SARS-CoV-2. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Then the positive clones were sequenced and reconstituted into whole human IgG for epitope binning assays. After that, all 19 IgG were classified into 6 different epitope groups or Bins. Although all these antibodies were shown to have ability to bind RBD, the antibodies in Bin2 have more superiority to inhibit the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 can also strongly bind with mutant RBDs (W463R, R408I, N354D, V367F and N354D/D364Y) derived from SARS-CoV-2 strain with increased infectivity, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 and its mutations. Furthermore, these neutralizing antibodies strongly restrict the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized pseudovirus entry into hACE2 overexpressed 293T cells. In Vero-E6 cells, these antibodies can even block the entry of live SARS-CoV-2 into cells at only 12.5 nM. These results suggest that these neutralizing human antibodies from the patient-derived antibody libraries have the potential to become therapeutic agents against SARS-CoV-2 and its mutants in this global pandemic.

Advances on the Asymptomatic Infection of COVID-19 / 中华流行病学杂志

The COVID-19 outbreak in China has been gradually controlled. At present, the management and risk assessment of asymptomatic infected cases has become an urgent problem to be addressed. Asymptomatic case is mainly detected by close contact screening, cluster epidemic investigation, infection source tracking investigation, and active detection of target population. Currently, research on the spread risk from asymptomatic cases was limited, and lacking the data relates to the distribution of asymptomatic cases in large community population. Pathogen detection using PCR is suitable for screening in close contacts of confirmed cases and should be started as early as possible. The antibody test is more suitable for screening in general population where the source of infection is unclear. The management of asymptomatic cases now in China focuses on isolation and medical observation according to the guideline of 'early detection, early report, early isolation and early treatment' .

Advances on presymptomatic or asymptomatic carrier transmission of COVID-19 / 中华流行病学杂志

COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of "the degree to which presymptomatic or asymptomatic infections can transmit" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.

Analysis on the heritability of diabetes, based on data from the Chinese adult twins / 中华流行病学杂志

Objective@#To analyze the heritability of diabetes among the Chinese twin adults.@*Methods@#A total of 10 253 same-sex twin pairs aged 25 years and older, were selected from the Chinese National Twin Registry (CNTR) program. Heritability of diabetes was calculated by using the structural equation model.@*Results@#After adjusted for age and gender, the overall heritability rates of diabetes were 0.41 (0.15-0.75), 0.83 (0.72-0.91) and 0.34 (0.04-0.73) in the <45 and ≥45 years twin pairs, respectively. After adjusted for age, rates of heritability appeared as 0.37 (0.05-0.78) and 0.88 (0.79-0.94) in men and women, respectively.@*Conclusions@#Diabetes is affected by both genetic and environmental factors. The genetic effect of diabetes seemed stronger on female than that on male twins but was dying down along with ageing.

Evaluation of immediate effectiveness of intervention on HIV prevention and leadership of POL among young male students who have sex with men in a city / 中国学校卫生

Objective@#To evaluate the immediate effectiveness of intervention on HIV prevention and leadership of POL among young male students who have sex with men in a city, and to provide reference for health education of AIDS.@*Methods@#A life-skills based participatory approach was adopted to intervene the AIDS prevention and leadership of 54 POL in young male students who have sex with men in a city. A unified questionnaire was adopted before and after the intervention to investigate and evaluate the effects.@*Results@#After intervention, the scores of AIDS prevention information increased from (36.30±7.30) points to (42.09±3.43) points (P<0.01). In terms of motivation, the scores of experience and attitude of condom-using were increased from (5.43±1.19) points to (5.83±1.24) points (P<0.05). As for the behavioral skills, the scores of condom-use skills increased from (4.30±1.04) points to (4.85±0.53) points (P<0.01), the scores of condom self-efficacy increased from (55.85±12.40) points to (61.48±8.01) points (P<0.01), the scores of autonomic HIV testing ability increased from (4.11±1.09) points to (4.65±0.52) points (P<0.01), the ability to avoid alcohol consumption before sexual behavior increased from (3.74±1.19) points to (4.13±0.91) points(P<0.05), and the ability to correctly seek medical advice after illness increased from (9.33±1.32) points to (9.69±0.77) points(P<0.05). In the part of the leadership, the scores of peer status increased from (26.96±5.55) points to (29.81±6.68) points (P<0.01), the scores of active communication ability increased from (21.35±5.76) points to (24.43±4.17) points (P<0.01), and the scores of psychosocial ability increased from (77.96±13.42) points to (80.89±12.42) points (P<0.05).@*Conclusion@#Life-skill-based intervention, which is guided by Information-Motivation-Behavioral skills model, is effective in improving AIDS prevention and leadership.

Fujian Tulou Family Cohort Study: study design and characteristics of participants and pedigrees in baseline investigation / 中华流行病学杂志

Objective To describe the study design,the characteristics of participants as well as the pedigrees included in the baseline survey of Fujian Tulou Family Cohort Study.Methods Fujian Tulou Family Cohort Study was a prospective open cohort study with a biological sample bank.A baseline survey was conducted in Tulou areas of Nanjing county in Fujian province from 2015 to 2018,including questionnaire survey,physical and biochemical indicators examinations,and blood sample collection in adults aged ≥ 18 years.In addition,family relationship of the participants was also recorded.The pedigree information of the juveniles under 18 years old were also collected.Results The baseline survey included 2 727 individuals in two clans,of whom 2 373 (87.0％) were adults,and 2 126 participants completed questionnaires,physical examinations and biochemical tests.The average age of the 2 126 participants was (57.9 ± 13.3) years,with 39.4％ being males.The current smoking rates in male and female participants were 41.2％ and 2.1％,respectively.The corresponding rates of current alcohol consumption were 19.0％ and 2.6％.For common chronic diseases,the prevalence rates were 51.3％ for hypertension,9.7％ for diabetes and 26.7％ for hyperlipemia according to the self-reported disease diagnoses,health examination results and biochemical examination results in class 1Ⅱor Ⅲ hospitals.Based on the family relationship information and genealogical data,710 pedigrees were finally identified,consisting of 5 087 family members.The numbers of five,four,three,and two generations pedigrees were 3,88,238 and 381,respectively.The pairs of the first to the fifth degree relatives were 12 039,2 662,1 511,202 and 31,respectively.Conclusion The establishment of Fujian Tulou Family Cohort provides valuable resources for exploring the genetic risk factors,environmental risk factors and gene-environment interactions contributing to the risk of common chronic diseases.

Effect of family environment in childhood and adolescence on mental health in adulthood / 中华流行病学杂志

Objective To explore the relationship of family environment in childhood and adolescence and mental health in adulthood.Methods A total of 791 subjects aged ≥25 years were selected through the Chinese National Twin Registry (CNTR).The short-form of Family Environment Scale-Chinese Version (FES-CV) was used to evaluate the family environment during childhood and adolescence in three dimensions:relationship,system maintenance and personal growth.The mental health status in adulthood was assessed with the Chinese version of 6-item Kessler Psychological Distress Scale (K6).The generalized linear mixed model was used to examine their relationship.Results About 4.6％ of the subjects reported general or worse mental health status.Compared with the subjects with good mental status,statistical difference was observed only in parenting way among twins (living together or not).After adjusting the potential confounders,such as age,sex,zygosity,education and lifestyle (smoking,drinking and physical activity),good family relationship and system maintenance had a positive effect on mental health,with the OR (95％CI) of 0.66 (0.5 1-0.87) and 0.70 (0.50-0.98) respectively.Furthermore,parenting way did not modify the effect of family environment on mental health status in adulthood (interaction:P＞0.05).In each scale,scores of cohesion and organization were positively correlated with mental health,while the score of conflict was negatively correlated with the mental health.Conclusion Good family relationship and system maintenance in childhood and adolescence had a positive impact on mental health in adulthood.

Association between obesity and DNA methylation among the 7-16 year-old twins / 中华流行病学杂志

Objective On whole-genome scale,we tried to explore the correlation between obesity-related traits and DNA methylation sites,based on discordant monozygotic twin pairs.Methods A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district,Yanqing district and Fangshan district in Beijing in 2016.Information on twins was gathered through a self-designed questionnaire and results from physical examination,including height,weight and waist circumference of the subjects under study.DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip.R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes.Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs).VarFit function of emp irical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups.Results According to the obesity discordance criteria,we collected 23 pairs of twins (age range 7 to 16 years),including 12 male pairs.A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis.According to the significance level of FDR set as ＜0.05,no positive sites would meet this standard.When DMC CpG site cg05684382,with the smallest P value (1.26E-06) as on chromosome 12,the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16.Conclusions In this study,we analyzed the genome-wide DNA methylation and its correlation with obesity traits.After multiple testing corrections,no positive sites were found to have associated with obesity.However,results from the correlation analysis demonstrated sites cg05684382 (chr:12) and cg26188191 (chr:16) might have played a role in the development of obesity.This study provides a methodologic reference for the studies on discordance twins related problems.

Fujian Tulou Family Cohort Study: study design and characteristics of participants and pedigrees in baseline investigation / 中华流行病学杂志

Objective To describe the study design,the characteristics of participants as well as the pedigrees included in the baseline survey of Fujian Tulou Family Cohort Study.Methods Fujian Tulou Family Cohort Study was a prospective open cohort study with a biological sample bank.A baseline survey was conducted in Tulou areas of Nanjing county in Fujian province from 2015 to 2018,including questionnaire survey,physical and biochemical indicators examinations,and blood sample collection in adults aged ≥ 18 years.In addition,family relationship of the participants was also recorded.The pedigree information of the juveniles under 18 years old were also collected.Results The baseline survey included 2 727 individuals in two clans,of whom 2 373 (87.0％) were adults,and 2 126 participants completed questionnaires,physical examinations and biochemical tests.The average age of the 2 126 participants was (57.9 ± 13.3) years,with 39.4％ being males.The current smoking rates in male and female participants were 41.2％ and 2.1％,respectively.The corresponding rates of current alcohol consumption were 19.0％ and 2.6％.For common chronic diseases,the prevalence rates were 51.3％ for hypertension,9.7％ for diabetes and 26.7％ for hyperlipemia according to the self-reported disease diagnoses,health examination results and biochemical examination results in class 1Ⅱor Ⅲ hospitals.Based on the family relationship information and genealogical data,710 pedigrees were finally identified,consisting of 5 087 family members.The numbers of five,four,three,and two generations pedigrees were 3,88,238 and 381,respectively.The pairs of the first to the fifth degree relatives were 12 039,2 662,1 511,202 and 31,respectively.Conclusion The establishment of Fujian Tulou Family Cohort provides valuable resources for exploring the genetic risk factors,environmental risk factors and gene-environment interactions contributing to the risk of common chronic diseases.

Effect of family environment in childhood and adolescence on mental health in adulthood / 中华流行病学杂志

Objective To explore the relationship of family environment in childhood and adolescence and mental health in adulthood.Methods A total of 791 subjects aged ≥25 years were selected through the Chinese National Twin Registry (CNTR).The short-form of Family Environment Scale-Chinese Version (FES-CV) was used to evaluate the family environment during childhood and adolescence in three dimensions:relationship,system maintenance and personal growth.The mental health status in adulthood was assessed with the Chinese version of 6-item Kessler Psychological Distress Scale (K6).The generalized linear mixed model was used to examine their relationship.Results About 4.6％ of the subjects reported general or worse mental health status.Compared with the subjects with good mental status,statistical difference was observed only in parenting way among twins (living together or not).After adjusting the potential confounders,such as age,sex,zygosity,education and lifestyle (smoking,drinking and physical activity),good family relationship and system maintenance had a positive effect on mental health,with the OR (95％CI) of 0.66 (0.5 1-0.87) and 0.70 (0.50-0.98) respectively.Furthermore,parenting way did not modify the effect of family environment on mental health status in adulthood (interaction:P＞0.05).In each scale,scores of cohesion and organization were positively correlated with mental health,while the score of conflict was negatively correlated with the mental health.Conclusion Good family relationship and system maintenance in childhood and adolescence had a positive impact on mental health in adulthood.

Association between obesity and DNA methylation among the 7-16 year-old twins / 中华流行病学杂志

Objective On whole-genome scale,we tried to explore the correlation between obesity-related traits and DNA methylation sites,based on discordant monozygotic twin pairs.Methods A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district,Yanqing district and Fangshan district in Beijing in 2016.Information on twins was gathered through a self-designed questionnaire and results from physical examination,including height,weight and waist circumference of the subjects under study.DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip.R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes.Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs).VarFit function of emp irical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups.Results According to the obesity discordance criteria,we collected 23 pairs of twins (age range 7 to 16 years),including 12 male pairs.A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis.According to the significance level of FDR set as ＜0.05,no positive sites would meet this standard.When DMC CpG site cg05684382,with the smallest P value (1.26E-06) as on chromosome 12,the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16.Conclusions In this study,we analyzed the genome-wide DNA methylation and its correlation with obesity traits.After multiple testing corrections,no positive sites were found to have associated with obesity.However,results from the correlation analysis demonstrated sites cg05684382 (chr:12) and cg26188191 (chr:16) might have played a role in the development of obesity.This study provides a methodologic reference for the studies on discordance twins related problems.

Association between birth cohort and the heritability of body mass index / 中华流行病学杂志

Objective To investigate the varying variances of the genetic components in birth cohorts.Methods Twin samples used in the current study were collected from the Chinese National Twin Registry and a two-wave study was conducted,in Qingdao and Lishui regions.Samples were broken down by birth cohort to create four subgroups:-1958,1959-1961,1962-1970 and 1970-.Structural equation models were fitted in each subgroup to estimate the genetic and environmental variances.Results From each birth cohort,weight and body mass index in 2012 appeared higher than those in 2001.Twins of 1971-cohort subgroup showed lower weight than in the other cohort subgroups.Except for the 1959-1961 cohort subgroup,the later birth cohorts were inversely related to the body mass indexes.Genetic factors might explain 54％-76％ of the total variations on the body mass index.Heritability of body mass index of twins born during 1959-1961 was increasing along with age.Conclusion Genetic factors might explain the main portion which related to the phenotypic variance of body mass index.Effects of genetic factors on body mass index of twins born during 1959-1961 might have increased along with age.

The Chinese national twin cohort: an update / 中华流行病学杂志

The importance of large cohort studies in China has been increasingly emphasized.As special group in the population,twins provide excellent natural resources since they share the same birthday,maternal intrauterine environment and early family environment.Twin cohorts are unique for and benefit on controlling the confounding factors as age,gender (same-sex twins),genetic background (monozygotic twins) or early environment (being raised together) in the etiological studies on complex diseases.In this review,we briefly introduce the objectives,current situation,challenges and opportunities related to the Chinese national twin cohort,focusing on the characteristics of twins that are different from other groups in the general population.

Mendelian randomization analysis of the relationship between obesity and DNA methylation / 中华预防医学杂志

Objective@#To explore the association between DNA methylation and body mass index (BMI) using Mendelian randomization analysis.@*Methods@#A total of 469 participants were selected from the Chinese National Twin Registry in 2013, who were living in Shandong, Jiangsu, Zhejiang, and Sichuan provinces, and at least 18 years of age. A questionnaire survey and physical examination were conducted to collect demographic, clinical, and behavioral information. Peripheral blood cells were collected to detect genotype and methylation status. Association analyses between DNA methylation and BMI and between CpGs and cis-SNP were conducted. With rs748212 as the instrumental variable, the association between cg15053022 and BMI was explored using the Mendelian randomization method.@*Results@#A total of 469 participants were selected. The mean age of participants was (44.8±13.2) years and the BMI was (25.0±3.8) kg/m2. Nine BMI-related DNA methylation sites were found and DNA methylation site cg15053022 in the ATP4A gene was negatively associated with cis-SNP rs748212 (β=-0.020); the mean methylation level of AA, AC, and CC were 0.212±0.025, 0.242±0.024, and 0.264±0.028, respectively. rs748212 was associated with BMI (β=0.04, P=0.007) and closely related to cg15053022 (F=237.66, P=0.143). Mendelian randomization analysis showed lower methylation levels at cg15053022 were associated with higher BMI (β=-1.97, P<0.001).@*Conclusion@#This study supported the impact of cg15053022 methylation in the ATP4A gene on BMI using Mendelian randomization analysis and provided the basis for using Mendelian randomization analysis in methylation studies.

Association between birth cohort and the heritability of body mass index / 中华流行病学杂志

Objective To investigate the varying variances of the genetic components in birth cohorts.Methods Twin samples used in the current study were collected from the Chinese National Twin Registry and a two-wave study was conducted,in Qingdao and Lishui regions.Samples were broken down by birth cohort to create four subgroups:-1958,1959-1961,1962-1970 and 1970-.Structural equation models were fitted in each subgroup to estimate the genetic and environmental variances.Results From each birth cohort,weight and body mass index in 2012 appeared higher than those in 2001.Twins of 1971-cohort subgroup showed lower weight than in the other cohort subgroups.Except for the 1959-1961 cohort subgroup,the later birth cohorts were inversely related to the body mass indexes.Genetic factors might explain 54％-76％ of the total variations on the body mass index.Heritability of body mass index of twins born during 1959-1961 was increasing along with age.Conclusion Genetic factors might explain the main portion which related to the phenotypic variance of body mass index.Effects of genetic factors on body mass index of twins born during 1959-1961 might have increased along with age.

The Chinese national twin cohort: an update / 中华流行病学杂志

The importance of large cohort studies in China has been increasingly emphasized.As special group in the population,twins provide excellent natural resources since they share the same birthday,maternal intrauterine environment and early family environment.Twin cohorts are unique for and benefit on controlling the confounding factors as age,gender (same-sex twins),genetic background (monozygotic twins) or early environment (being raised together) in the etiological studies on complex diseases.In this review,we briefly introduce the objectives,current situation,challenges and opportunities related to the Chinese national twin cohort,focusing on the characteristics of twins that are different from other groups in the general population.